CompletedNCT03306264Updated Aug 27, 2024Results posted

Study of ASTX727 vs IV Decitabine in Participants With MDS, CMML, and AML

A Phase 3 interventional study of ASTX727 and Dacogen in Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia and Acute Myeloid Leukemia, sponsored by Astex Pharmaceuticals, Inc.. Completed at 84 sites in 10 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-08-27.

Sponsored by Astex Pharmaceuticals, Inc. · Phase 3, Interventional, and Treatment

Phase: Phase 3
Study type: Interventional
Enrollment: 227
Allocation: Randomized
Ages: 18 Years and older
Sex: All

Study summary

Multicenter PK study of ASTX727 versus IV decitabine. Adult participants who were candidates to receive IV decitabine were randomized 1:1 to receive the ASTX727 tablet Daily×5 in Cycle 1 followed by IV decitabine 20 mg/m\^2 Daily×5 in Cycle 2, or the converse order. After completion of PK studies during the first 2 treatment cycles, participants continued to receive treatment with ASTX727 from Cycle 3 onward (in 28-day cycles) until disease progression, unacceptable toxicity, or the participants discontinued treatment or withdrew from the study.

Read the detailed description

This Phase 3 study established PK equivalence of ASTX727 to IV decitabine in approximately 227 evaluable participants. Eligible participants were randomized to receive both study treatments: oral investigational drug ASTX727, and IV decitabine, as follows: participants were randomly assigned 1:1 to receive ASTX727 or IV decitabine in Cycle 1 and then cross over to the other therapy in Cycle 2.

In the ASTX727 cycle, participants received the ASTX727 tablet Daily×5. Serial PK measurements (blood draws) were done on Days 1, 2, and 5, along with pre-dose PK assessments on Days 1-5 and an assessment at 3 hours post-dose on Day 3. Participants were required to fast from food for 4 hours on days when receiving ASTX727: at least 2 hours before and 2 hours after dosing.

In the IV decitabine cycle, participants received a 1-hour infusion of IV decitabine 20 mg/m\^2 Daily×5. Serial PK measurements were done on Days 1 and 5, along with pre-dose and 1-hour post-infusion assessments on Day 3.

In Cycles ≥3, participants received the ASTX727 tablet Daily×5 in 28-day cycles. (No PK assessments were done from Cycle 3 onward.)

Conditions studied

Myelodysplastic Syndromes
Chronic Myelomonocytic Leukemia
Acute Myeloid Leukemia

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Keywords

MDS
CMML
decitabine
Myelodysplastic Syndromes
Chronic Myelomonocytic Leukemia
Acute Myeloid Leukemia
AML

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

Able to understand and comply with the study procedures, understand the risks involved in the study, and provide written informed consent before the first study-specific procedure; specifically able to comply with the PK assessment schedule during the first 2 treatment cycles.
Men or women ≥18 years who are candidates to receive IV decitabine according to FDA or European Medicines Agency (EMA) approved indications:
1. In North America: Participants with MDS previously treated or untreated with de novo or secondary MDS, including all French-American-British subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia [CMML]), and subjects with MDS International Prognostic Scoring System (IPSS) int-1, -2, or high-risk MDS.
2. In Europe: Participants with de novo or secondary AML, as defined by the World Health Organization (WHO) criteria, who are not candidates for standard induction chemotherapy.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
Adequate organ function defined as follows:
1. Hepatic: Total or direct bilirubin ≤2 × upper limit of normal (ULN); aspartate transaminase/serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine transaminase/serum glutamic pyruvic transaminase (ALT/SGPT) ≤2.5 × ULN.
2. Renal: serum creatinine ≤1.5 × ULN or calculated creatinine clearance or glomerular filtration rate >50 mL/min/1.73 m2 for subjects with creatinine levels above institutional normal.
No major surgery within 30 days of first study treatment.
Life expectancy of at least 3 months.
Women of child-bearing potential must not be pregnant or breastfeeding and must have a negative pregnancy test at screening. Women of non-childbearing potential are those who have had a hysterectomy or bilateral oophorectomy, or who have completed menopause, defined as no menses for at least 1 year AND either age ≥65 years or follicle-stimulating hormone levels in the menopausal range.
Subjects and their partners with reproductive potential must agree to use effective contraceptive measures during the study and for 3 months after the last dose of study treatment. Effective contraception includes methods such as oral contraceptives or double-barrier method (eg, use of a condom AND diaphragm, with spermicide).

Exclusion criteria

Exclusion Criteria:

Prior treatment with more than 1 cycle of azacitidine or decitabine. Prior cytotoxic chemotherapy for AML except for hydroxyurea to control high white blood cell (WBC) counts.
Hospitalization for more than 2 days for documented febrile neutropenia, pneumonia, sepsis, or systemic infection in the 30 days before screening.
Treatment with any investigational drug or therapy within 2 weeks of study treatment, or 5 half-lives, whichever is longer, before the first dose of study treatment, or ongoing clinically significant adverse events (AEs) from previous treatment.
Cytotoxic chemotherapy or prior azacitidine or decitabine within 4 weeks of first dose of study treatment.
Concurrent MDS therapies, including lenalidomide, erythropoietin, cyclosporine/tacrolimus, granulocyte-colony stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor, etc. (Prior treatment with these agents is permitted, provided that completion is at least 1 week before the first dose of study treatment.)
Poor medical risk because of other conditions such as uncontrolled systemic diseases, active uncontrolled infections, or comorbidities that may put the patient at risk of not being able to complete at least 2 cycles of treatment.
Known significant mental illness or other condition, such as active alcohol or other substance abuse or addiction, that in the opinion of the investigator predisposes the subject to high risk of noncompliance with the protocol.
Rapidly progressive or highly proliferative disease (total white blood cell count of >15 × 10\^9/L) or other criteria that render the subject at high risk of requiring intensive cytotoxic chemotherapy within the next 3 months.
Life-threatening illness or severe organ system dysfunction, such as uncontrolled congestive heart failure or chronic obstructive pulmonary disease, or other reasons including laboratory abnormalities, which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of ASTX727, or compromise completion of the study or integrity of the study outcomes.
Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, prostate cancer or breast cancer under control with hormone therapy, or other cancer from which the subject has been disease free for at least 2 years.

Study design

Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover assignment
Masking: None (open label)
Enrollment: 227 participants (actual)

Study arms

Experimental
MDS or CMML: Sequence A: First ASTX727, Then IV Decitabine, Then ASTX727
Participants with MDS or CMML received ASTX727 tablet, containing the fixed-dose combination of 35 mg decitabine and 100 mg cedazuridine, orally, once daily, on Days 1 to 5 in cycle 1 (each cycle = 28 days), followed by IV infusion of decitabine 20 mg/m\^2, once daily, on Days 1 to 5 in cycle 2. A washout period of 23 days was maintained between the 2 cycles. From cycle 3, all participants enrolled in cycles 1 and 2 received ASTX727 tablet, once daily, on Days 1 to 5 of each 28-day cycle until disease progression, unacceptable toxicity, treatment discontinuation for other reasons, or withdrawal from the study.
Drug: ASTX727 · Drug: Dacogen
Experimental
MDS or CMML: Sequence B: First IV Decitabine, Then ASTX727, Then ASTX727
Participants with MDS or CMML received IV infusion of decitabine 20 mg/m\^2, once daily, on Days 1 to 5 in cycle 1 (each cycle = 28 days) followed by ASTX727 tablet, containing the fixed-dose combination of 35 mg decitabine and 100 mg cedazuridine, orally, once daily, on Days 1 to 5 in cycle 2. A washout period of 23 days was maintained between the 2 cycles. From cycle 3, all participants enrolled in cycles 1 and 2 received ASTX727 tablet, once daily, on Days 1 to 5 of each 28-day cycle until disease progression, unacceptable toxicity, treatment discontinuation for other reasons, or withdrawal from the study.
Drug: ASTX727 · Drug: Dacogen
Experimental
AML: Sequence A: First ASTX727, Then IV Decitabine, Then ASTX727
Participants with AML received ASTX727 tablet, containing the fixed-dose combination of 35 mg decitabine and 100 mg cedazuridine, orally, once daily, on Days 1 to 5 in cycle 1 (each cycle = 28 days), followed by IV infusion of decitabine 20 mg/m\^2, once daily, on Days 1 to 5 in cycle 2. A washout period of 23 days was maintained between the 2 cycles. From cycle 3, all participants enrolled in cycles 1 and 2 received ASTX727 tablet, once daily, on Days 1 to 5 of each 28-day cycle until disease progression, unacceptable toxicity, participant discontinued treatment, or was withdrawn from the study.
Drug: ASTX727 · Drug: Dacogen
Experimental
AML: Sequence B: First IV Decitabine, Then ASTX727, Then ASTX727
Participants with AML received IV infusion of decitabine 20 mg/m\^2, once daily, on Days 1 to 5 in cycle 1 (each cycle = 28 days) followed by ASTX727 tablet, containing the fixed-dose combination of 35 mg decitabine and 100 mg cedazuridine, orally, once daily, on Days 1 to 5 in cycle 2. A washout period of 23 days was maintained between the 2 cycles. From cycle 3, all participants enrolled in cycles 1 and 2 received ASTX727 tablet, once daily, on Days 1 to 5 of each 28-day cycle until disease progression, unacceptable toxicity, participant discontinued treatment, or was withdrawn from the study.
Drug: ASTX727 · Drug: Dacogen

Interventions

DrugASTX727
ASTX727 oral tablet
Also known as: decitabine 35 mg + cedazuridine 100 mg
DrugDacogen
Decitabine 20 mg/m\^2 one-hour IV infusion
Also known as: decitabine

What researchers measure

Primary outcomes

Total 5-day Area Under the Curve From 0 to 24 Hours (AUC0-24) After Treatment With ASTX727 And IV Decitabine
Total 5-day ASTX727 AUC0-24 exposures were calculated using PK data from 3 days of serial PK sampling, Day 1 AUC0-24 (first ASTX727 dose) was added to (Day 2 AUC0-24+ Day 5 AUC0-24) × 2. Decitabine 5-day AUC0-24 exposures after IV decitabine were calculated as follows: (Day 1 AUC0-24+ Day 5 AUC0-24) / 2 was multiplied by 5. If AUC0-24 on Day 2 (for ASTX727) or Day 1 (IV decitabine) was not available, it was replaced by AUC0-24 on Day 5; the converse was also true.
Time frame: ASTX727: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post-dose on Days 1 to 5 of Cycle 1 and 2; Decitabine: Pre-dose, 0.25, 0.5, 1, 1.08, 1.5, 2, 3, 4, 6, 8 hours post-dose on Days 1 to 5 of Cycle 1 and 2 (each cycle= 28 days)

Secondary outcomes

MDS/CMML: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
An AE is defined as any untoward medical occurrence in a clinical investigation participants administered a drug; it does not necessarily have to have a causal relationship with this treatment. TEAEs were defined as events that first occurred or worsened on or after the date of the first dose of study treatment until 30 days after the last dose of study treatment or until the start of a post-treatment alternative anti-cancer treatment, whichever occurred first.
Time frame: From randomization up to 30 days after last dose of study treatment (up to approximately 2.7 years)
AML: Number of Participants With Treatment-emergent Adverse Events (AEs)
An AE is defined as any untoward medical occurrence in a clinical investigation participants administered a drug; it does not necessarily have to have a causal relationship with this treatment. TEAEs were defined as events that first occurred or worsened on or after the date of the first dose of study treatment until 30 days after the last dose of study treatment or until the start of a post-treatment alternative anti-cancer treatment, whichever occurred first.
Time frame: From randomization up to 30 days after last dose of study treatment (up to approximately 2.4 years)
MDS/CMML: Number of Participants With Grade 3 or Higher TEAEs
TEAEs were defined as events that first occurred or worsened on or after the date of the first dose of study treatment until 30 days after the last dose of study treatment or until the start of a post-treatment alternative anti-cancer treatment, whichever occurred first. Severity of AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Fatal.
Time frame: From randomization up to 30 days after last dose of study treatment (up to approximately 2.7 years)
AML: Number of Participants With Grade 3 or Higher TEAEs
TEAEs were defined as events that first occurred or worsened on or after the date of the first dose of study treatment until 30 days after the last dose of study treatment or until the start of a post-treatment alternative anti-cancer treatment, whichever occurred first. Severity of AEs were graded using CTCAE version 4.03. Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Fatal.
Time frame: From randomization up to 30 days after last dose of study treatment (up to approximately 2.4 years)
Maximum Percentage of Long Interspersed Nucleotide Elements (LINE)-1 Demethylation
Summarized data for Cycle 1 and Cycle 2 was reported.
Time frame: Pre-dose on Day 1 of Cycles 1 and 2 (as Baseline), and Days 8, 15 and 22 of Cycles 1 and 2 (each cycle= 28 days)
Total 5-day Area Under the Curve From 0 to Infinity (AUC0-inf) After Treatment With ASTX727 And IV Decitabine
Total 5-day ASTX727 AUC0-inf exposures were calculated using PK data from 3 days of serial PK sampling, Day 1 AUC0-inf (first ASTX727 dose) was added to (Day 2 AUC0-inf+ Day 5 AUC0-inf) × 2. Decitabine 5-day AUC0-inf exposures after IV decitabine were calculated as follows: (Day 1 AUC0-inf+ Day 5 AUC0-inf) / 2 was multiplied by 5. If AUC0-inf on Day 2 (for ASTX727) or Day 1 (IV decitabine) was not available, it was replaced by AUC0-inf on Day 5; the converse was also true.
Time frame: ASTX727: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post-dose on Days 1 to 5 of Cycle 1 and 2; Decitabine: Pre-dose, 0.25, 0.5, 1, 1.08, 1.5, 2, 3, 4, 6, 8 hours post-dose on Days 1 to 5 of Cycle 1 and 2 (each cycle= 28 days)
Total 5-day Area Under the Curve From 0 to Last Quantifiable Concentration (AUC0-last) After Treatment With ASTX727 And IV Decitabine
Total 5-day ASTX727 AUC0-last exposures were calculated using PK data from 3 days of serial PK sampling, Day 1 AUC0-last (first ASTX727 dose) was added to (Day 2 AUC0-last + Day 5 AUC0-last) × 2. Decitabine 5-day AUC0-last exposures after IV decitabine were calculated as follows: (Day 1 AUC0-last + Day 5 AUC0-last) / 2 was multiplied by 5. If AUC0-last on Day 2 (for ASTX727) or Day 1 (IV decitabine) was not available, it was replaced by AUC0-last on Day 5; the converse was also true.
Time frame: ASTX727: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post-dose on Days 1 to 5 of Cycle 1 and 2; Decitabine: Pre-dose, 0.25, 0.5, 1, 1.08, 1.5, 2, 3, 4, 6, 8 hours post-dose on Days 1 to 5 of Cycle 1 and 2 (each cycle= 28 days)
Total 5-day Area Under the Curve From 0 to 8 Hours (AUC0-8) After Treatment With ASTX727 And IV Decitabine
Total 5-day ASTX727 AUC0-8 exposures were calculated using PK data from 3 days of serial PK sampling, Day 1 AUC0-8 (first ASTX727 dose) was added to (Day 2 AUC0-8 + Day 5 AUC0-8) × 2. Decitabine 5-day AUC0-8 exposures after IV decitabine were calculated as follows: (Day 1 AUC0-8 + Day 5 AUC0-8) / 2 was multiplied by 5. If AUC0-8 on Day 2 (for ASTX727) or Day 1 (IV decitabine) was not available, it was replaced by AUC0-8 on Day 5; the converse was also true.
Time frame: ASTX727: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post-dose on Days 1 to 5 of Cycle 1 and 2; Decitabine: Pre-dose, 0.25, 0.5, 1, 1.08, 1.5, 2, 3, 4, 6, 8 hours post-dose on Days 1 to 5 of Cycle 1 and 2 (each cycle= 28 days)
Area Under the Curve From 0 to Infinity (AUC0-inf) After Treatment With ASTX727 And IV Decitabine
AUC0-inf was calculated using the formula AUClast + (Clast / λZ), where Clast is the last quantifiable concentration and λZ is the elimination rate constant. AUC0-inf will be calculated using the linear up-log down method. Summarized data has been reported for cycle 1 and 2.
Time frame: ASTX727: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post-dose on Days 1, 2 and 5 of Cycle 1 and 2; Decitabine: Pre-dose, 0.25, 0.5, 1, 1.08, 1.5, 2, 3, 4, 6, 8 hours post-dose on Days 1 and 5 of Cycle 1 and 2 (each cycle= 28 days)
Maximum Observed Plasma Concentration (Cmax) of Decitabine, Cedazuridine, and Cedazuridine-epimer
Summarized data of Cmax on Day 1, 2 and 5 respectively for Cycle 1 and 2 has been reported for ASTX727. Similarly, summarized data of Cmax on Day 1 and 5 respectively for Cycle 1 and 2 has been reported for IV Decitabine.
Time frame: ASTX727: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post-dose on Days 1, 2 and 5 of Cycle 1 and 2; Decitabine: Pre-dose, 0.25, 0.5, 1, 1.08, 1.5, 2, 3, 4, 6, 8 hours post-dose on Days 1 and 5 of Cycle 1 and 2 (each cycle= 28 days)
Time to Reach Maximum Plasma Concentration (Tmax) of Decitabine, Cedazuridine, and Cedazuridine-epimer
Summarized data of Tmax on Day 1, 2 and 5 respectively for Cycle 1 and 2 has been reported for ASTX727. Similarly, summarized data of Tmax on Day 1 and 5 respectively for Cycle 1 and 2 has been reported for IV Decitabine.
Time frame: ASTX727: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post-dose on Days 1, 2 and 5 of Cycle 1 and 2; Decitabine: Pre-dose, 0.25, 0.5, 1, 1.08, 1.5, 2, 3, 4, 6, 8 hours post-dose on Days 1 and 5 of Cycle 1 and 2 (each cycle= 28 days)
Apparent Oral Clearance (CL/F) of Oral Decitabine and Cedazuridine
Oral CL/F for oral decitabine was measured only on Day 1 and oral CL/F for oral cedazuridine was measured on Days 1, 2 and 5. Summarized data of Oral CL/F for oral decitabine on Day 1 for Cycle 1 and 2 has been reported for ASTX727. Similarly, summarized data of oral CL/F for oral cedazuridine on Day 1,2 and 5 respectively for Cycle 1 and 2 has been reported for ASTX727.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post-dose on Days 1, 2 and 5 of Cycle 1 and 2 (each cycle= 28 days)
Apparent Elimination Half Life (t1/2) of Decitabine, Cedazuridine, and Cedazuridine-epimer
Summarized data of t1/2 on Day 1, 2 and 5 respectively for Cycle 1 and 2 has been reported for ASTX727. Similarly, summarized data of t1/2 on Day 1 and 5 respectively for Cycle 1 and 2 has been reported for IV Decitabine.
Time frame: ASTX727: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post-dose on Days 1, 2 and 5 of Cycle 1 and 2; Decitabine: Pre-dose, 0.25, 0.5, 1, 1.08, 1.5, 2, 3, 4, 6, 8 hours post-dose on Days 1 and 5 of Cycle 1 and 2 (each cycle= 28 days)
Apparent Volume of Distribution (Vz/F) of Oral Decitabine and Cedazuridine
Summarized data of Vz/F on Day 1, 2 and 5 respectively for Cycle 1 and 2 has been reported for ASTX727.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post-dose on Days 1, 2 and 5 of Cycle 1 and 2 (each cycle= 28 days)
MDS/CMML: Percentage of Participants With Complete Response (CR), Marrow CR (mCR), Partial Response (PR), Hematologic Improvement (HI) Based on International Working Group (IWG) 2006 Myelodysplastic Syndromes (MDS) Response Criteria
CR: normal peripheral, persistent granulocyte count ≥1.0x10\^9/liter(L), platelet ≥100x10\^9/L, Hemoglobin (Hgb) ≥11g/dL, normal bone marrow with persistent marrow blasts ≤5%. mCR: reduction of bone marrow blasts to≤5%, decrease by 50% or more with/without normalization of peripheral counts.PR: normal peripheral counts, granulocyte count ≥1.0x10\^9/L, platelet count ≥100x10\^9/L, Hgb ≥11 g/dL, normal bone marrow, marrow blasts \>5%, reduced by 50% or more for at least 4 weeks. HI: HI-E: Hb increase ≥1.5 g/dL in absence of RBC transfusions. HI-P: Absolute increase of platelet count from \<20 to \>20X10\^9/L by at least 100%,if more than 20x10\^9/L, by absolute increase of at least 30x10\^9/L in absence of platelet transfusions. HI-N: granulocyte increase ≥100%, by an absolute increase ≥0.5x10\^9/L for at least 8 weeks. Percentage of participants with CR, mCR, PR, and HI based on IWG 2003 MDS response criteria are reported. Response has been reported based on participants with MDS or CMML.
Time frame: Up to approximately 2.7 years
AML: Percentage of Participants With CR, CR With Incomplete Blood Count Recovery (CRi), CR With Incomplete Platelet Recovery (CRp), and CR Plus CRp Based on IWG 2003 AML Response Criteria
CR was defined as absolute neutrophil content (ANC) ≥1000/ microliter (μL), platelets ≥100,000/μL, independence from red blood cell (RBC) and platelet transfusions over the past week, no leukemic blasts and \<5% leukemic blasts. CRp was defined as CR criteria except platelets \<100,000/μL.and platelet transfusion over the past week. CRi was defined as CR criteria except ANC \<1000/μL or platelets \<100,000/μL. Percentage of participants with CR, CRi, CRp, and CR Plus CRp based on IWG 2003 AML response criteria are reported.
Time frame: Up to approximately 2.4 years
AML: Percentage of Participants With CR With Partial Hematologic Recovery (CRh) Based on IWG 2003 AML Response Criteria
CRh was defined as \<5% of blasts in the bone marrow, no evidence of disease, and partial recovery of peripheral blood counts (platelets \>50,000/μL and ANC \>500/μL), independence from RBC and platelet transfusions within 7 days of bone marrow evaluation, and peripheral blast ≤1%. Percentage of participants with CRh based on IWG 2003 AML response criteria are reported.
Time frame: Day 1 of Cycle 3 up to approximately 2.4 years (each cycle= 28 days)
AML: Time to First Response, Best Response and Complete Response Based on IWG 2003 AML Response Criteria
Time to first response was defined as time in months from the date of first treatment to the first date when any response is achieved. Time to best response was defined in months from the date of first treatment to the first date when a subject's best response, in the order of CR, CRi (or CRp or CRh), or PR, was achieved. Time to CR was defined in months from the date of first treatment to the first date when CR is achieved. CR:ANC ≥1000/ microliter (μL),platelets ≥100,000/μL,independence from RBC and platelet transfusions over the past week, no leukemic blasts, and \<5% leukemic blasts.CRp: CR criteria except ANC ≥1000/μL, platelets \< 100,000/μL.and platelet transfusion over the past week. CRi:CR criteria except ANC \<1000/μL or platelets \<100,000/μL.CRh: \<5% of blasts in the bone marrow,platelets \>50,000/μL and ANC \>500/μL, independence from RBC and platelet transfusions within 7 days and peripheral blast ≤1%. PR: CR criteria except decrease of ≥50% in leukemic blasts.
Time frame: Up to approximately 2.4 years
AML: Duration of Complete Response and Combined CR and CRh Based on IWG 2003 AML Response Criteria
Duration of CR was defined as the time interval from the first CR to time of relapse. Duration of combined CR and CRh was defined as the time interval from the first CR or CRh to time of relapse. Duration of CR and combined CR and CRh was presented using a Kaplan-Meier estimate.
Time frame: Up to approximately 2.4 years
MDS/CMML: Percentage of Participants With Red Blood Cell (RBC) and Platelet Transfusion Independence (TI)
Transfusion independence was defined as no transfusion for 56 consecutive days or more (84 and 112 days) after the first dose of study treatment while maintaining hemoglobin ≥8 grams/deciliter (g/dL) (RBC TI) or maintaining platelets ≥20×109/L (platelet TI).
Time frame: Up to approximately 2.7 years
AML: Percentage of Participants With Red Blood Cell (RBC) and Platelet Transfusion Independence (TI)
Transfusion independence was defined as no transfusion for 56 consecutive days or more (112 days) after the first dose of study treatment while maintaining hemoglobin ≥8 grams/deciliter (g/dL) (RBC TI) or maintaining platelets ≥20×109/L (platelet TI).
Time frame: Up to approximately 2.4 years
MDS/CMML: Leukemia-free Survival (LFS)
LFS was defined as time from the date of randomization to the date when bone marrow or peripheral blood blasts reach ≥20%, or death from any cause. Participants who hadn't reached AML at the time of the analysis were censored at the date of the last follow-up. Leukemia-free survival was presented using a Kaplan-Meier estimate.
Time frame: From randomization up to approximately 2.7 years
MDS/CMML: Overall Survival (OS)
OS was defined as time from the date of randomization to the date of death from any cause. Participants without documented death at the time of the analysis were censored at the date of the last follow-up. Overall survival was presented using a Kaplan-Meier estimate.
Time frame: From randomization up to approximately 2.7 years
AML: Overall Survival (OS)
OS was defined as time from the date of randomization to the date of death from any cause. Participants without documented death at the time of the analysis were censored at the date of the last follow-up. Overall survival was presented using a Kaplan-Meier estimate.
Time frame: From randomization up to approximately 2.4 years
AML: Survival Rates at 6 Months, 1 Year, and 2 Years
One-year survival rate was defined as the survival rate at the end of the first year from the date of randomization. The survival rates at 6 months and at 2 years were calculated similarly.
Time frame: At Month 6, Year 1 and 2
AML: Event-free Survival (EFS)
EFS was defined as time from the date of randomization to the date of treatment failure \[disease progression/relapse (due to confirmed reappearance of leukemic blasts in peripheral blood or ≥5% leukemic blasts in bone marrow (including relapse), discontinue treatment due to disease progression or treatment-related AE, or alternative anti-leukemia therapy except for HCT\] or death from any cause, whichever occurs first. Participants without documented treatment failure at the time of the analysis were censored at the date of the last follow-up. Event-free survival was presented using a Kaplan-Meier estimate.
Time frame: From randomization up to approximately 2.4 years
AML: Progression-free Survival (PFS)
PFS was defined as time from the date of randomization to the date disease progression due to confirmed reappearance of leukemic blasts in peripheral blood or ≥5% leukemic blasts in bone marrow (including relapse) or death from any cause, whichever occurs first. Participants without documented disease progression/relapse or death at the time of the analysis were censored at the date of the last follow-up. Progression-free survival was presented using a Kaplan-Meier estimate.
Time frame: From randomization up to approximately 2.4 years

Results

Posted Jul 1, 2024

Participant flow

A total of 227 participants took part in the study from 15 February 2018 to 25 May 2023. 138 participants with a diagnosis of myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML) took part from the United States and Canada. 89 participants with a diagnosis of acute myeloid leukemia (AML) took part from Austria, Canada, Czech Republic, France, Germany, Hungary, Italy, Spain, and United Kingdom.

Participant flow — Overall Study
Milestone	MDS or CMML: Sequence A: First ASTX727, Then IV Decitabine, Then ASTX727	MDS or CMML: Sequence B: First IV Decitabine, Then ASTX727, Then ASTX727	AML: Sequence A: First ASTX727, Then IV Decitabine, Then ASTX727	AML: Sequence B: First IV Decitabine, Then ASTX727, Then ASTX727
Started	69	69	44	45
Safety analysis set	66	67	43	44
Completed	0	0	0	0
Not completed	69	69	44	45
Withdrew: Death	33	25	34	34
Withdrew: Complete consent withdrawal	4	4	1	8
Withdrew: Lost to follow-up	1	0	1	0
Withdrew: Rollover to astx727-06	10	18	4	2
Withdrew: Study centre terminated by sponsor	21	22	4	1

Outcome measures

PrimaryTotal 5-day Area Under the Curve From 0 to 24 Hours (AUC0-24) After Treatment With ASTX727 And IV Decitabine

Total 5-day ASTX727 AUC0-24 exposures were calculated using PK data from 3 days of serial PK sampling, Day 1 AUC0-24 (first ASTX727 dose) was added to (Day 2 AUC0-24+ Day 5 AUC0-24) × 2. Decitabine 5-day AUC0-24 exposures after IV decitabine were calculated as follows: (Day 1 AUC0-24+ Day 5 AUC0-24) / 2 was multiplied by 5. If AUC0-24 on Day 2 (for ASTX727) or Day 1 (IV decitabine) was not available, it was replaced by AUC0-24 on Day 5; the converse was also true.

Time frame:: ASTX727: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post-dose on Days 1 to 5 of Cycle 1 and 2; Decitabine: Pre-dose, 0.25, 0.5, 1, 1.08, 1.5, 2, 3, 4, 6, 8 hours post-dose on Days 1 to 5 of Cycle 1 and 2 (each cycle= 28 days)
Reported as:: Geometric mean · hours*nanograms per milliliter (h*ng/mL)

Total 5-day Area Under the Curve From 0 to 24 Hours (AUC0-24) After Treatment With ASTX727 And IV Decitabine
hoursnanograms per milliliter (hng/mL)	MDS or CMML: IV Decitabine	MDS or CMML: ASTX727	AML: IV Decitabine	AML: ASTX727
Total 5-day Area Under the Curve From 0 to 24 Hours (AUC0-24) After Treatment With ASTX727 And IV Decitabine	864.34 ± 40.0	855.96 ± 50.6	910.1 ± 52.4	900.5 ± 52.0

Statistical analysis

MDS or CMML: IV Decitabine vs MDS or CMML: ASTX727 · Ratio of geometric lsm: 98.93 · 90% CI 92.66 to 105.6Analysis was based on ANOVA model with treatment, cycle, and sequence as fixed effects, and participant nested in sequence as a random effect (ratio is Oral/IV).
AML: IV Decitabine vs AML: ASTX727 · Ratio of geometric lsm: 99.64 · 90% CI 91.23 to 108.8Analysis was based on ANOVA model with treatment, cycle, and sequence as fixed effects, and participant nested in sequence as a random effect (ratio is Oral/IV).

SecondaryMDS/CMML: Number of Participants With Treatment-emergent Adverse Events (TEAEs)

An AE is defined as any untoward medical occurrence in a clinical investigation participants administered a drug; it does not necessarily have to have a causal relationship with this treatment. TEAEs were defined as events that first occurred or worsened on or after the date of the first dose of study treatment until 30 days after the last dose of study treatment or until the start of a post-treatment alternative anti-cancer treatment, whichever occurred first.

Time frame:: From randomization up to 30 days after last dose of study treatment (up to approximately 2.7 years)
Reported as:: Count of participants · Participants

MDS/CMML: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Participants	MDS or CMML: IV Decitabine	MDS or CMML: ASTX727
MDS/CMML: Number of Participants With Treatment-emergent Adverse Events (TEAEs)	127	130

SecondaryAML: Number of Participants With Treatment-emergent Adverse Events (AEs)

Time frame:: From randomization up to 30 days after last dose of study treatment (up to approximately 2.4 years)
Reported as:: Count of participants · Participants

AML: Number of Participants With Treatment-emergent Adverse Events (AEs)
Participants	AML: IV Decitabine	AML: ASTX727
AML: Number of Participants With Treatment-emergent Adverse Events (AEs)	71	80

SecondaryMDS/CMML: Number of Participants With Grade 3 or Higher TEAEs

TEAEs were defined as events that first occurred or worsened on or after the date of the first dose of study treatment until 30 days after the last dose of study treatment or until the start of a post-treatment alternative anti-cancer treatment, whichever occurred first. Severity of AEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Fatal.

Time frame:: From randomization up to 30 days after last dose of study treatment (up to approximately 2.7 years)
Reported as:: Count of participants · Participants

MDS/CMML: Number of Participants With Grade 3 or Higher TEAEs
Participants	MDS or CMML: IV Decitabine	MDS or CMML: ASTX727
MDS/CMML: Number of Participants With Grade 3 or Higher TEAEs	89	121

SecondaryAML: Number of Participants With Grade 3 or Higher TEAEs

TEAEs were defined as events that first occurred or worsened on or after the date of the first dose of study treatment until 30 days after the last dose of study treatment or until the start of a post-treatment alternative anti-cancer treatment, whichever occurred first. Severity of AEs were graded using CTCAE version 4.03. Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Fatal.

Time frame:: From randomization up to 30 days after last dose of study treatment (up to approximately 2.4 years)
Reported as:: Count of participants · Participants

AML: Number of Participants With Grade 3 or Higher TEAEs
Participants	AML: IV Decitabine	AML: ASTX727
AML: Number of Participants With Grade 3 or Higher TEAEs	43	73

SecondaryMaximum Percentage of Long Interspersed Nucleotide Elements (LINE)-1 Demethylation

Summarized data for Cycle 1 and Cycle 2 was reported.

Time frame:: Pre-dose on Day 1 of Cycles 1 and 2 (as Baseline), and Days 8, 15 and 22 of Cycles 1 and 2 (each cycle= 28 days)
Reported as:: Least squares mean · percentage of demethylation

Maximum Percentage of Long Interspersed Nucleotide Elements (LINE)-1 Demethylation
percentage of demethylation	MDS or CMML: IV Decitabine	MDS or CMML: ASTX727	AML: IV Decitabine	AML: ASTX727
Cycle 1	14.019 (12.528 to 15.510)	13.289 (11.798 to 14.780)	8.243 (6.340 to 10.147)	9.357 (7.288 to 11.426)
Cycle 2	11.968 (10.503 to 13.434)	11.151 (9.685 to 12.616)	8.153 (6.226 to 10.079)	8.037 (6.258 to 9.816)

SecondaryTotal 5-day Area Under the Curve From 0 to Infinity (AUC0-inf) After Treatment With ASTX727 And IV Decitabine

Total 5-day ASTX727 AUC0-inf exposures were calculated using PK data from 3 days of serial PK sampling, Day 1 AUC0-inf (first ASTX727 dose) was added to (Day 2 AUC0-inf+ Day 5 AUC0-inf) × 2. Decitabine 5-day AUC0-inf exposures after IV decitabine were calculated as follows: (Day 1 AUC0-inf+ Day 5 AUC0-inf) / 2 was multiplied by 5. If AUC0-inf on Day 2 (for ASTX727) or Day 1 (IV decitabine) was not available, it was replaced by AUC0-inf on Day 5; the converse was also true.

Time frame:: ASTX727: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post-dose on Days 1 to 5 of Cycle 1 and 2; Decitabine: Pre-dose, 0.25, 0.5, 1, 1.08, 1.5, 2, 3, 4, 6, 8 hours post-dose on Days 1 to 5 of Cycle 1 and 2 (each cycle= 28 days)
Reported as:: Geometric least squares mean · h*ng/mL

Total 5-day Area Under the Curve From 0 to Infinity (AUC0-inf) After Treatment With ASTX727 And IV Decitabine
h*ng/mL	MDS or CMML: IV Decitabine	MDS or CMML: ASTX727	AML: IV Decitabine	AML: ASTX727
Total 5-day Area Under the Curve From 0 to Infinity (AUC0-inf) After Treatment With ASTX727 And IV Decitabine	866.15 ± 39.9	849.63 ± 50.4	912.3 ± 52.3	902.1 ± 51.8

Statistical analysis

MDS or CMML: IV Decitabine vs MDS or CMML: ASTX727 · Ratio of geometric lsm: 98.00 · 90% CI 91.80 to 104.6Analysis was based on ANOVA model with treatment, cycle, and sequence as fixed effects, and participant nested in sequence as a random effect (ratio is Oral/IV).
AML: IV Decitabine vs AML: ASTX727 · Ratio of geometric lsm: 99.61 · 90% CI 91.20 to 108.8Analysis was based on ANOVA model with treatment, cycle, and sequence as fixed effects, and participant nested in sequence as a random effect (ratio is Oral/IV).

SecondaryTotal 5-day Area Under the Curve From 0 to Last Quantifiable Concentration (AUC0-last) After Treatment With ASTX727 And IV Decitabine

Total 5-day ASTX727 AUC0-last exposures were calculated using PK data from 3 days of serial PK sampling, Day 1 AUC0-last (first ASTX727 dose) was added to (Day 2 AUC0-last + Day 5 AUC0-last) × 2. Decitabine 5-day AUC0-last exposures after IV decitabine were calculated as follows: (Day 1 AUC0-last + Day 5 AUC0-last) / 2 was multiplied by 5. If AUC0-last on Day 2 (for ASTX727) or Day 1 (IV decitabine) was not available, it was replaced by AUC0-last on Day 5; the converse was also true.

Time frame:: ASTX727: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post-dose on Days 1 to 5 of Cycle 1 and 2; Decitabine: Pre-dose, 0.25, 0.5, 1, 1.08, 1.5, 2, 3, 4, 6, 8 hours post-dose on Days 1 to 5 of Cycle 1 and 2 (each cycle= 28 days)
Reported as:: Geometric mean · h*ng/mL

Total 5-day Area Under the Curve From 0 to Last Quantifiable Concentration (AUC0-last) After Treatment With ASTX727 And IV Decitabine
h*ng/mL	MDS or CMML: IV Decitabine	MDS or CMML: ASTX727	AML: IV Decitabine	AML: ASTX727
Total 5-day Area Under the Curve From 0 to Last Quantifiable Concentration (AUC0-last) After Treatment With ASTX727 And IV Decitabine	853.02 ± 40.7	837.38 ± 50.7	902.7 ± 53.0	881.8 ± 52.5

Statistical analysis

MDS or CMML: IV Decitabine vs MDS or CMML: ASTX727 · Ratio of geometric lsm: 98.11 · 90% CI 91.88 to 104.8Analysis was based on ANOVA model with treatment, cycle, and sequence as fixed effects, and participant nested in sequence as a random effect (ratio is Oral/IV).
AML: IV Decitabine vs AML: ASTX727 · Ratio of geometric lsm: 98.11 · 90% CI 89.75 to 107.2Analysis was based on ANOVA model with treatment, cycle, and sequence as fixed effects, and participant nested in sequence as a random effect (ratio is Oral/IV).

SecondaryTotal 5-day Area Under the Curve From 0 to 8 Hours (AUC0-8) After Treatment With ASTX727 And IV Decitabine

Total 5-day ASTX727 AUC0-8 exposures were calculated using PK data from 3 days of serial PK sampling, Day 1 AUC0-8 (first ASTX727 dose) was added to (Day 2 AUC0-8 + Day 5 AUC0-8) × 2. Decitabine 5-day AUC0-8 exposures after IV decitabine were calculated as follows: (Day 1 AUC0-8 + Day 5 AUC0-8) / 2 was multiplied by 5. If AUC0-8 on Day 2 (for ASTX727) or Day 1 (IV decitabine) was not available, it was replaced by AUC0-8 on Day 5; the converse was also true.

Time frame:: ASTX727: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post-dose on Days 1 to 5 of Cycle 1 and 2; Decitabine: Pre-dose, 0.25, 0.5, 1, 1.08, 1.5, 2, 3, 4, 6, 8 hours post-dose on Days 1 to 5 of Cycle 1 and 2 (each cycle= 28 days)
Reported as:: Geometric mean · h*ng/mL

Total 5-day Area Under the Curve From 0 to 8 Hours (AUC0-8) After Treatment With ASTX727 And IV Decitabine
h*ng/mL	MDS or CMML: IV Decitabine	MDS or CMML: ASTX727	AML: IV Decitabine	AML: ASTX727
Total 5-day Area Under the Curve From 0 to 8 Hours (AUC0-8) After Treatment With ASTX727 And IV Decitabine	856.63 ± 40.6	839.37 ± 50.4	910.1 ± 52.0	883.8 ± 52.1

Statistical analysis

MDS or CMML: IV Decitabine vs MDS or CMML: ASTX727 · Ratio of geometric lsm: 97.93 · 90% CI 91.74 to 104.5Analysis was based on ANOVA model with treatment, cycle, and sequence as fixed effects, and participant nested in sequence as a random effect (ratio is Oral/IV).
AML: IV Decitabine vs AML: ASTX727 · Ratio of geometric lsm: 97.55 · 90% CI 89.32 to 106.5Analysis was based on ANOVA model with treatment, cycle, and sequence as fixed effects, and participant nested in sequence as a random effect (ratio is Oral/IV).

SecondaryArea Under the Curve From 0 to Infinity (AUC0-inf) After Treatment With ASTX727 And IV Decitabine

AUC0-inf was calculated using the formula AUClast + (Clast / λZ), where Clast is the last quantifiable concentration and λZ is the elimination rate constant. AUC0-inf will be calculated using the linear up-log down method. Summarized data has been reported for cycle 1 and 2.

Time frame:: ASTX727: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post-dose on Days 1, 2 and 5 of Cycle 1 and 2; Decitabine: Pre-dose, 0.25, 0.5, 1, 1.08, 1.5, 2, 3, 4, 6, 8 hours post-dose on Days 1 and 5 of Cycle 1 and 2 (each cycle= 28 days)
Reported as:: Geometric mean · nanograms*hours per millilitres(ng*h/mL)

Area Under the Curve From 0 to Infinity (AUC0-inf) After Treatment With ASTX727 And IV Decitabine
nanogramshours per millilitres(ngh/mL)	MDS or CMML: IV Decitabine	MDS or CMML: ASTX727	AML: IV Decitabine	AML: ASTX727
Day 1	174 ± 40.8	102 ± 54.8	175 ± 54.9	118 ± 54.4
Day 2	—	186 ± 55.3	—	193 ± 59.6
Day 5	170 ± 41.7	178 ± 52.7	181 ± 58.1	187 ± 57.1

SecondaryMaximum Observed Plasma Concentration (Cmax) of Decitabine, Cedazuridine, and Cedazuridine-epimer

Summarized data of Cmax on Day 1, 2 and 5 respectively for Cycle 1 and 2 has been reported for ASTX727. Similarly, summarized data of Cmax on Day 1 and 5 respectively for Cycle 1 and 2 has been reported for IV Decitabine.

Time frame:: ASTX727: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post-dose on Days 1, 2 and 5 of Cycle 1 and 2; Decitabine: Pre-dose, 0.25, 0.5, 1, 1.08, 1.5, 2, 3, 4, 6, 8 hours post-dose on Days 1 and 5 of Cycle 1 and 2 (each cycle= 28 days)
Reported as:: Geometric mean · nanogram per milliliter (ng/mL)

Maximum Observed Plasma Concentration (Cmax) of Decitabine, Cedazuridine, and Cedazuridine-epimer
nanogram per milliliter (ng/mL)	MDS or CMML: IV Decitabine	MDS or CMML: ASTX727	AML: IV Decitabine	AML: ASTX727
Decitabine: Day 1	184 ± 48.1	83.1 ± 66.1	187 ± 64.7	85.9 ± 56.6
Decitabine: Day 2	—	145 ± 54.7	—	139 ± 58.5
Decitabine: Day 5	180 ± 49.2	140 ± 62.8	192 ± 62.4	139 ± 62.7
Cedazuridine: Day 1	—	321 ± 53.8	—	313 ± 47.7
Cedazuridine: Day 2	—	349 ± 49.1	—	343 ± 43.4
Cedazuridine: Day 5	—	371 ± 51.8	—	350 ± 42.7
Cedazuridine-epimer: Day 1	—	150 ± 65.7	—	182 ± 60.0
Cedazuridine-epimer: Day 2	—	155 ± 64.6	—	204 ± 59.2
Cedazuridine-epimer: Day 5	—	169 ± 65.9	—	191 ± 58.4

SecondaryTime to Reach Maximum Plasma Concentration (Tmax) of Decitabine, Cedazuridine, and Cedazuridine-epimer

Summarized data of Tmax on Day 1, 2 and 5 respectively for Cycle 1 and 2 has been reported for ASTX727. Similarly, summarized data of Tmax on Day 1 and 5 respectively for Cycle 1 and 2 has been reported for IV Decitabine.

Time frame:: ASTX727: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post-dose on Days 1, 2 and 5 of Cycle 1 and 2; Decitabine: Pre-dose, 0.25, 0.5, 1, 1.08, 1.5, 2, 3, 4, 6, 8 hours post-dose on Days 1 and 5 of Cycle 1 and 2 (each cycle= 28 days)
Reported as:: Median · hours

Time to Reach Maximum Plasma Concentration (Tmax) of Decitabine, Cedazuridine, and Cedazuridine-epimer
hours	MDS or CMML: IV Decitabine	MDS or CMML: ASTX727	AML: IV Decitabine	AML: ASTX727
Decitabine: Day 1	0.98 (0.23 to 1.27)	1.00 (0.48 to 3.00)	0.98 (0.25 to 2.00)	1.00 (0.25 to 2.02)
Decitabine: Day 2	—	1.00 (0.47 to 2.00)	—	1.00 (0.25 to 3.00)
Decitabine: Day 5	0.97 (0.25 to 1.62)	1.00 (0.25 to 3.00)	0.98 (0.00 to 1.17)	1.00 (0.47 to 3.00)
Cedazuridine: Day 1	—	3.00 (1.50 to 7.97)	—	3.98 (1.47 to 8.00)
Cedazuridine: Day 2	—	3.01 (0.52 to 7.88)	—	4.00 (1.00 to 7.88)
Cedazuridine: Day 5	—	3.00 (1.50 to 6.12)	—	3.98 (1.00 to 8.00)
Cedazuridine-epimer: Day 1	—	3.08 (1.50 to 7.97)	—	4.00 (1.50 to 8.03)
Cedazuridine-epimer: Day 2	—	3.03 (0.52 to 7.88)	—	4.00 (1.50 to 7.88)
Cedazuridine-epimer: Day 5	—	3.08 (1.00 to 8.05)	—	4.00 (1.53 to 8.00)

SecondaryApparent Oral Clearance (CL/F) of Oral Decitabine and Cedazuridine

Oral CL/F for oral decitabine was measured only on Day 1 and oral CL/F for oral cedazuridine was measured on Days 1, 2 and 5. Summarized data of Oral CL/F for oral decitabine on Day 1 for Cycle 1 and 2 has been reported for ASTX727. Similarly, summarized data of oral CL/F for oral cedazuridine on Day 1,2 and 5 respectively for Cycle 1 and 2 has been reported for ASTX727.

Time frame:: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post-dose on Days 1, 2 and 5 of Cycle 1 and 2 (each cycle= 28 days)
Reported as:: Geometric mean · Litres per hour (L/h)

Apparent Oral Clearance (CL/F) of Oral Decitabine and Cedazuridine
Litres per hour (L/h)	MDS or CMML: ASTX727	AML: ASTX727
Decitabine: Day 1	342 ± 54.8	297 ± 54.4
Cedazuridine: Day 1	30.6 ± 46.4	28.6 ± 55.5
Cedazuridine: Day 2	25.6 ± 159	27.4 ± 45.4
Cedazuridine: Day 5	16.8 ± 15.9	86.8 ± NA

SecondaryApparent Elimination Half Life (t1/2) of Decitabine, Cedazuridine, and Cedazuridine-epimer

Summarized data of t1/2 on Day 1, 2 and 5 respectively for Cycle 1 and 2 has been reported for ASTX727. Similarly, summarized data of t1/2 on Day 1 and 5 respectively for Cycle 1 and 2 has been reported for IV Decitabine.

Time frame:: ASTX727: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post-dose on Days 1, 2 and 5 of Cycle 1 and 2; Decitabine: Pre-dose, 0.25, 0.5, 1, 1.08, 1.5, 2, 3, 4, 6, 8 hours post-dose on Days 1 and 5 of Cycle 1 and 2 (each cycle= 28 days)
Reported as:: Geometric mean · hours

Apparent Elimination Half Life (t1/2) of Decitabine, Cedazuridine, and Cedazuridine-epimer
hours	MDS or CMML: IV Decitabine	MDS or CMML: ASTX727	AML: IV Decitabine	AML: ASTX727
Decitabine: Day 1	0.967 ± 46.8	1.18 ± 22.8	1.16 ± 56.7	1.07 ± 31.6
Decitabine: Day 2	—	1.38 ± 24.7	—	1.36 ± 35.0
Decitabine: Day 5	1.14 ± 44.9	1.47 ± 26.9	1.18 ± 49.0	1.45 ± 34.0
Cedazuridine: Day 1	—	6.33 ± 18.1	—	6.68 ± 18.5
Cedazuridine: Day 2	—	6.70 ± 18.9	—	7.05 ± 17.6
Cedazuridine: Day 5	—	2.59 ± 5.43	—	2.41 ± NA
Cedazuridine-epimer: Day 1	—	5.50 ± 21.8	—	6.22 ± 17.4
Cedazuridine-epimer: Day 2	—	5.90 ± 23.2	—	6.15 ± 22.8
Cedazuridine-epimer: Day 5	—	2.58 ± 5.16	—	2.57 ± NA

SecondaryApparent Volume of Distribution (Vz/F) of Oral Decitabine and Cedazuridine

Summarized data of Vz/F on Day 1, 2 and 5 respectively for Cycle 1 and 2 has been reported for ASTX727.

Time frame:: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post-dose on Days 1, 2 and 5 of Cycle 1 and 2 (each cycle= 28 days)
Reported as:: Geometric mean · Litres

Apparent Volume of Distribution (Vz/F) of Oral Decitabine and Cedazuridine
Litres	MDS or CMML: ASTX727	AML: ASTX727
Decitabine: Day 1	585 ± 55.0	434 ± 60.4
Decitabine: Day 2	369 ± 59.0	337 ± 67.6
Decitabine: Day 5	417 ± 54.3	373 ± 68.9
Cedazuridine: Day 1	280 ± 50.9	272 ± 59.9
Cedazuridine: Day 2	296 ± 51.3	278 ± 49.8
Cedazuridine: Day 5	62.8 ± 10.4	302 ± NA

SecondaryMDS/CMML: Percentage of Participants With Complete Response (CR), Marrow CR (mCR), Partial Response (PR), Hematologic Improvement (HI) Based on International Working Group (IWG) 2006 Myelodysplastic Syndromes (MDS) Response Criteria

CR: normal peripheral, persistent granulocyte count ≥1.0x10\^9/liter(L), platelet ≥100x10\^9/L, Hemoglobin (Hgb) ≥11g/dL, normal bone marrow with persistent marrow blasts ≤5%. mCR: reduction of bone marrow blasts to≤5%, decrease by 50% or more with/without normalization of peripheral counts.PR: normal peripheral counts, granulocyte count ≥1.0x10\^9/L, platelet count ≥100x10\^9/L, Hgb ≥11 g/dL, normal bone marrow, marrow blasts \>5%, reduced by 50% or more for at least 4 weeks. HI: HI-E: Hb increase ≥1.5 g/dL in absence of RBC transfusions. HI-P: Absolute increase of platelet count from \<20 to \>20X10\^9/L by at least 100%,if more than 20x10\^9/L, by absolute increase of at least 30x10\^9/L in absence of platelet transfusions. HI-N: granulocyte increase ≥100%, by an absolute increase ≥0.5x10\^9/L for at least 8 weeks. Percentage of participants with CR, mCR, PR, and HI based on IWG 2003 MDS response criteria are reported. Response has been reported based on participants with MDS or CMML.

Time frame:: Up to approximately 2.7 years
Reported as:: Number · percentage of participants

MDS/CMML: Percentage of Participants With Complete Response (CR), Marrow CR (mCR), Partial Response (PR), Hematologic Improvement (HI) Based on International Working Group (IWG) 2006 Myelodysplastic Syndromes (MDS) Response Criteria
percentage of participants	MDS: Sequence A: First ASTX727, Then IV Decitabine, Then ASTX727	MDS: Sequence B: First IV Decitabine, Then ASTX727, Then ASTX727	CMML: Sequence A: First ASTX727, Then IV Decitabine, Then ASTX727	CMML: Sequence B: First IV Decitabine, Then ASTX727, Then ASTX727
Complete Response (CR)	26.2 (15.8 to 39.1)	19.6 (10.2 to 32.4)	0 (0 to 0)	18.2 (2.3 to 51.8)
Marrow Complete Response (mCR)	29.5 (18.5 to 42.6)	30.4 (18.8 to 44.1)	40.0 (5.3 to 85.3)	54.5 (23.4 to 83.3)
Partial Response (PR)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)
HI: Erythroid Response (HI-E)	0 (0 to 0)	1.8 (0.0 to 9.6)	20.0 (0.5 to 71.6)	0 (0 to 0)
HI: Platelet Response (HI-P)	3.3 (0.4 to 11.3)	8.9 (3.0 to 19.6)	0 (0 to 0)	0 (0 to 0)
HI: Neutrophil Response (HI-N)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	9.1 (0.2 to 41.3)

SecondaryAML: Percentage of Participants With CR, CR With Incomplete Blood Count Recovery (CRi), CR With Incomplete Platelet Recovery (CRp), and CR Plus CRp Based on IWG 2003 AML Response Criteria

CR was defined as absolute neutrophil content (ANC) ≥1000/ microliter (μL), platelets ≥100,000/μL, independence from red blood cell (RBC) and platelet transfusions over the past week, no leukemic blasts and \<5% leukemic blasts. CRp was defined as CR criteria except platelets \<100,000/μL.and platelet transfusion over the past week. CRi was defined as CR criteria except ANC \<1000/μL or platelets \<100,000/μL. Percentage of participants with CR, CRi, CRp, and CR Plus CRp based on IWG 2003 AML response criteria are reported.

Time frame:: Up to approximately 2.4 years
Reported as:: Number · percentage of participants

AML: Percentage of Participants With CR, CR With Incomplete Blood Count Recovery (CRi), CR With Incomplete Platelet Recovery (CRp), and CR Plus CRp Based on IWG 2003 AML Response Criteria
percentage of participants	AML: Sequence A: First ASTX727, Then IV Decitabine, Then ASTX727	AML: Sequence B: First IV Decitabine, Then ASTX727, Then ASTX727
Complete Response (CR)	14.0 (5.3 to 27.9)	29.5 (16.8 to 45.2)
CR with Incomplete Platelet Recovery (CRp)	4.7 (0.6 to 15.8)	0 (0.0 to 8.0)
CR with Incomplete Blood Count Recovery (CRi)	11.6 (3.9 to 25.1)	0 (0.0 to 8.0)
CR Plus CRp	18.6 (8.4 to 33.4)	29.5 (16.8 to 45.2)

SecondaryAML: Percentage of Participants With CR With Partial Hematologic Recovery (CRh) Based on IWG 2003 AML Response Criteria

CRh was defined as \<5% of blasts in the bone marrow, no evidence of disease, and partial recovery of peripheral blood counts (platelets \>50,000/μL and ANC \>500/μL), independence from RBC and platelet transfusions within 7 days of bone marrow evaluation, and peripheral blast ≤1%. Percentage of participants with CRh based on IWG 2003 AML response criteria are reported.

Time frame:: Day 1 of Cycle 3 up to approximately 2.4 years (each cycle= 28 days)
Reported as:: Number · percentage of participants

AML: Percentage of Participants With CR With Partial Hematologic Recovery (CRh) Based on IWG 2003 AML Response Criteria
percentage of participants	AML: Sequence A: First ASTX727, Then IV Decitabine, Then ASTX727	AML: Sequence B: First IV Decitabine, Then ASTX727, Then ASTX727
AML: Percentage of Participants With CR With Partial Hematologic Recovery (CRh) Based on IWG 2003 AML Response Criteria	4.7 (0.6 to 15.8)	0 (0.0 to 8.0)

SecondaryAML: Time to First Response, Best Response and Complete Response Based on IWG 2003 AML Response Criteria

Time to first response was defined as time in months from the date of first treatment to the first date when any response is achieved. Time to best response was defined in months from the date of first treatment to the first date when a subject's best response, in the order of CR, CRi (or CRp or CRh), or PR, was achieved. Time to CR was defined in months from the date of first treatment to the first date when CR is achieved. CR:ANC ≥1000/ microliter (μL),platelets ≥100,000/μL,independence from RBC and platelet transfusions over the past week, no leukemic blasts, and \<5% leukemic blasts.CRp: CR criteria except ANC ≥1000/μL, platelets \< 100,000/μL.and platelet transfusion over the past week. CRi:CR criteria except ANC \<1000/μL or platelets \<100,000/μL.CRh: \<5% of blasts in the bone marrow,platelets \>50,000/μL and ANC \>500/μL, independence from RBC and platelet transfusions within 7 days and peripheral blast ≤1%. PR: CR criteria except decrease of ≥50% in leukemic blasts.

Time frame:: Up to approximately 2.4 years
Reported as:: Median · months

AML: Time to First Response, Best Response and Complete Response Based on IWG 2003 AML Response Criteria
months	AML: ASTX727 or IV Decitabine
Time to First Response	2.91 (1.9 to 6.5)
Time to Best Response	3.45 (1.9 to 7.5)
Time to Complete Response	3.02 (1.9 to 7.5)

SecondaryAML: Duration of Complete Response and Combined CR and CRh Based on IWG 2003 AML Response Criteria

Duration of CR was defined as the time interval from the first CR to time of relapse. Duration of combined CR and CRh was defined as the time interval from the first CR or CRh to time of relapse. Duration of CR and combined CR and CRh was presented using a Kaplan-Meier estimate.

Time frame:: Up to approximately 2.4 years
Reported as:: Median · months

AML: Duration of Complete Response and Combined CR and CRh Based on IWG 2003 AML Response Criteria
months	AML: ASTX727 or IV Decitabine
Duration of Complete Response	6.9 (3.4 to 11.5)
Duration of Combined CR and CRh	9.0 (3.4 to 11.5)

SecondaryMDS/CMML: Percentage of Participants With Red Blood Cell (RBC) and Platelet Transfusion Independence (TI)

Transfusion independence was defined as no transfusion for 56 consecutive days or more (84 and 112 days) after the first dose of study treatment while maintaining hemoglobin ≥8 grams/deciliter (g/dL) (RBC TI) or maintaining platelets ≥20×109/L (platelet TI).

Time frame:: Up to approximately 2.7 years
Reported as:: Number · percentage of participants

MDS/CMML: Percentage of Participants With Red Blood Cell (RBC) and Platelet Transfusion Independence (TI)
percentage of participants	MDS or CMML: ASTX727 or IV Decitabine
RBC TI: ≥56 Days	51.9 (37.8 to 65.7)
RBC TI: ≥84 Days	40.7 (27.6 to 55.0)
RBC TI: ≥112 Days	33.3 (21.1 to 47.5)
Platelet TI: ≥56 Days	50.0 (21.1 to 78.9)
Platelet TI: ≥84 Days	33.3 (9.9 to 65.1)
Platelet TI: ≥112 Days	33.3 (9.9 to 65.1)

SecondaryAML: Percentage of Participants With Red Blood Cell (RBC) and Platelet Transfusion Independence (TI)

Transfusion independence was defined as no transfusion for 56 consecutive days or more (112 days) after the first dose of study treatment while maintaining hemoglobin ≥8 grams/deciliter (g/dL) (RBC TI) or maintaining platelets ≥20×109/L (platelet TI).

Time frame:: Up to approximately 2.4 years
Reported as:: Number · percentage of participants

AML: Percentage of Participants With Red Blood Cell (RBC) and Platelet Transfusion Independence (TI)
percentage of participants	AML: ASTX727 or IV Decitabine
RBC TI ≥56 Days	37.8 (22.5 to 55.2)
RBC TI ≥112 Days	24.3 (11.8 to 41.2)
Platelet TI ≥56 Days	35.7 (12.8 to 64.9)
Platelet TI ≥112 Days	28.6 (8.4 to 58.1)

SecondaryMDS/CMML: Leukemia-free Survival (LFS)

LFS was defined as time from the date of randomization to the date when bone marrow or peripheral blood blasts reach ≥20%, or death from any cause. Participants who hadn't reached AML at the time of the analysis were censored at the date of the last follow-up. Leukemia-free survival was presented using a Kaplan-Meier estimate.

Time frame:: From randomization up to approximately 2.7 years
Reported as:: Median · days

MDS/CMML: Leukemia-free Survival (LFS)
days	MDS or CMML: ASTX727 or IV Decitabine
MDS/CMML: Leukemia-free Survival (LFS)	889.0 (674.0 to NA)

SecondaryMDS/CMML: Overall Survival (OS)

OS was defined as time from the date of randomization to the date of death from any cause. Participants without documented death at the time of the analysis were censored at the date of the last follow-up. Overall survival was presented using a Kaplan-Meier estimate.

Time frame:: From randomization up to approximately 2.7 years
Reported as:: Median · days

MDS/CMML: Overall Survival (OS)
days	MDS or CMML: ASTX727 or IV Decitabine
MDS/CMML: Overall Survival (OS)	966.0 (809.0 to NA)

SecondaryAML: Overall Survival (OS)

Time frame:: From randomization up to approximately 2.4 years
Reported as:: Median · months

AML: Overall Survival (OS)
months	AML: ASTX727 or IV Decitabine
AML: Overall Survival (OS)	8.9 (5.9 to 13.1)

SecondaryAML: Survival Rates at 6 Months, 1 Year, and 2 Years

One-year survival rate was defined as the survival rate at the end of the first year from the date of randomization. The survival rates at 6 months and at 2 years were calculated similarly.

Time frame:: At Month 6, Year 1 and 2
Reported as:: Number · percentage of participants

AML: Survival Rates at 6 Months, 1 Year, and 2 Years
percentage of participants	AML: ASTX727 or IV Decitabine
Month 6	61 (50 to 71)
Year 1	44 (33 to 54)
Year 2	16 (8 to 26)

SecondaryAML: Event-free Survival (EFS)

EFS was defined as time from the date of randomization to the date of treatment failure \[disease progression/relapse (due to confirmed reappearance of leukemic blasts in peripheral blood or ≥5% leukemic blasts in bone marrow (including relapse), discontinue treatment due to disease progression or treatment-related AE, or alternative anti-leukemia therapy except for HCT\] or death from any cause, whichever occurs first. Participants without documented treatment failure at the time of the analysis were censored at the date of the last follow-up. Event-free survival was presented using a Kaplan-Meier estimate.

Time frame:: From randomization up to approximately 2.4 years
Reported as:: Median · months

AML: Event-free Survival (EFS)
months	AML: ASTX727 or IV Decitabine
AML: Event-free Survival (EFS)	5.9 (3.8 to 8.5)

SecondaryAML: Progression-free Survival (PFS)

PFS was defined as time from the date of randomization to the date disease progression due to confirmed reappearance of leukemic blasts in peripheral blood or ≥5% leukemic blasts in bone marrow (including relapse) or death from any cause, whichever occurs first. Participants without documented disease progression/relapse or death at the time of the analysis were censored at the date of the last follow-up. Progression-free survival was presented using a Kaplan-Meier estimate.

Time frame:: From randomization up to approximately 2.4 years
Reported as:: Median · months

AML: Progression-free Survival (PFS)
months	AML: ASTX727 or IV Decitabine
AML: Progression-free Survival (PFS)	6.1 (4.0 to 8.7)

Adverse events

Collected over MDS or CMML: From randomization up to 2.7 years; AML: From randomization up to 2.4 years. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
MDS or CMML: IV Decitabine	2/132 (1.5%)	24/132 (18.2%)	127/132 (96.2%)
MDS or CMML: ASTX727	56/130 (43.1%)	81/130 (62.3%)	130/130 (100%)
MDS or CMML: Not Treated	0/5 (0%)	0/5 (0%)	0/5 (0%)
AML: IV Decitabine	5/78 (6.4%)	19/78 (24.4%)	70/78 (89.7%)
AML: ASTX727	61/80 (76.3%)	65/80 (81.3%)	76/80 (95%)
AML: Not Treated	2/2 (100%)	1/2 (50%)	0/2 (0%)

Most frequent serious events

Showing 10 of 147

Most frequent serious events
Event	MDS or CMML: IV Decitabine	MDS or CMML: ASTX727	MDS or CMML: Not Treated	AML: IV Decitabine	AML: ASTX727	AML: Not Treated
Sudden DeathGeneral disorders	0/132	0/130	0/5	0/78	1/80	1/2
Febrile neutropeniaBlood and lymphatic system disorders	8/132	33/130	0/5	4/78	21/80	0/2
PneumoniaInfections and infestations	6/132	17/130	0/5	4/78	16/80	0/2
SepsisInfections and infestations	0/132	10/130	0/5	0/78	3/80	0/2
InfectionInfections and infestations	0/132	0/130	0/5	1/78	5/80	0/2
AnaemiaBlood and lymphatic system disorders	0/132	2/130	0/5	0/78	4/80	0/2
CellulitisInfections and infestations	2/132	5/130	0/5	1/78	4/80	0/2
AstheniaGeneral disorders	1/132	2/130	0/5	0/78	3/80	0/2
Urinary tract infectionInfections and infestations	0/132	1/130	0/5	0/78	3/80	0/2
BronchitisInfections and infestations	0/132	0/130	0/5	0/78	3/80	0/2

Most frequent other events

Showing 10 of 88

Most frequent other events
Event	MDS or CMML: IV Decitabine	MDS or CMML: ASTX727	MDS or CMML: Not Treated	AML: IV Decitabine	AML: ASTX727	AML: Not Treated
ThrombocytopeniaBlood and lymphatic system disorders	52/132	90/130	0/5	30/78	47/80	0/2
NeutropeniaBlood and lymphatic system disorders	45/132	79/130	0/5	8/78	27/80	0/2
AnaemiaBlood and lymphatic system disorders	47/132	72/130	0/5	21/78	41/80	0/2
FatigueGeneral disorders	23/132	68/130	0/5	2/78	9/80	0/2
ConstipationGastrointestinal disorders	26/132	64/130	0/5	8/78	15/80	0/2
NauseaGastrointestinal disorders	23/132	63/130	0/5	4/78	17/80	0/2
DiarrhoeaGastrointestinal disorders	14/132	54/130	0/5	1/78	17/80	0/2
HeadacheNervous system disorders	19/132	50/130	0/5	2/78	6/80	0/2
DyspnoeaRespiratory, thoracic and mediastinal disorders	12/132	45/130	0/5	3/78	4/80	0/2
Decreased AppetiteMetabolism and nutrition disorders	7/132	43/130	0/5	5/78	12/80	0/2

Baseline characteristics

The Safety Analysis Set included all participants who received any amount of study treatment.

Age, Customized
Age, Customized(Participants)	MDS or CMML: ASTX727 or IV Decitabine	AML: ASTX727 or IV Decitabine	Total
18 to 64 years	36	3	39
65 to 84 years	93	75	168
≥85 years	4	9	13

Sex: Female, Male
Sex: Female, Male(Participants)	MDS or CMML: ASTX727 or IV Decitabine	AML: ASTX727 or IV Decitabine	Total
Female	46	34	80
Male	87	53	140

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	MDS or CMML: ASTX727 or IV Decitabine	AML: ASTX727 or IV Decitabine	Total
Hispanic or Latino	6	0	6
Not Hispanic or Latino	125	0	125
Unknown or Not Reported	2	87	89

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	MDS or CMML: ASTX727 or IV Decitabine	AML: ASTX727 or IV Decitabine	Total
American Indian or Alaska Native	0	0	0
Asian	3	0	3
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	4	0	4
White	121	0	121
More than one race	0	0	0
Unknown or Not Reported	5	87	92

Study locations

84 sites

Pinnacle Research Group
Anniston, Alabama 36207, United States
Mayo Clinic Arizona
Phoenix, Arizona 85054, United States
Arizona Clinical Research Center
Tucson, Arizona 85715, United States
Compassionate Cancer Care Research Group
Fountain Valley, California 92708, United States
University of Southern California
Los Angeles, California 90007, United States
Yale
New Haven, Connecticut 06510, United States
Georgetown University
Washington, District of Columbia 20007, United States
Boca Raton Clinical Research
Boca Raton, Florida 33322, United States
Holy Cross Hospital
Fort Lauderdale, Florida 33308, United States
Mount Sinai
Miami Beach, Florida 33140, United States
Rush University Medical Center
Chicago, Illinois 60612, United States
University of Chicago
Chicago, Illinois 60637, United States
Quincy Medical Group
Quincy, Illinois 62301, United States
Indiana Blood and Marrow Transplantation
Indianapolis, Indiana 46237, United States
Norton Cancer Institute
Louisville, Kentucky 40207, United States
Johns Hopkins
Baltimore, Maryland 21287, United States
Regional Cancer Care Associates
Bethesda, Maryland 20817, United States
Michigan Center of Medical Research
Farmington Hills, Michigan 48334, United States
Cancer & Hematology Centers of Western Michigan
Grand Rapids, Michigan 49503, United States
Mayo Clinic Rochester
Rochester, Minnesota 55905, United States
Hackensack
Hackensack, New Jersey 07601, United States
Montefiore
Bronx, New York 10467, United States
Roswell Park
Buffalo, New York 14263, United States
Monter Cancer Center
Lake Success, New York 11042, United States
Weill Cornell Medicine
New York, New York 10065, United States
Gabrail Cancer Center
Canton, Ohio 44718, United States
Ohio State University
Columbus, Ohio 43210, United States
Oregon Health & Sciences University
Portland, Oregon 20817, United States
West Penn Allegheny Cancer Institute
Pittsburgh, Pennsylvania 15224, United States
University of Pittsburgh Hillman Cancer Center
Pittsburgh, Pennsylvania 15232, United States
Charleston Hematology Oncology Associates
Charleston, South Carolina 29414, United States
Vanderbilt
Nashville, Tennessee 37232, United States
Baylor Scott & White University Medical Center
Dallas, Texas 75246, United States
University of Texas Southwestern Medical Center
Dallas, Texas 75390-9179, United States
Houston Methodist Cancer Center
Houston, Texas 77030, United States
MD Anderson Cancer Center
Houston, Texas 77030, United States
Utah Cancer Specialists
Salt Lake City, Utah 84124, United States
Kadlec Clinic Hematology and Oncology
Kennewick, Washington 99336, United States
Fred Hutchinson Cancer Research Center
Seattle, Washington 98109, United States
Uniklinikum Salzburg
Salzburg, 05020, Austria
General Hospital Hietzing
Vienna, 01130, Austria
Klinikum Wels-Grieskirchen
Wels, 4600, Austria
University of Alberta Hospital
Edmonton, Alberta T6G 2B7, Canada
Queen Elizabeth II (QEII) Health Sciences Center
Halifax, Nova Scotia B3H 2Y9, Canada
Juravinski Hospital & Cancer Center
Hamilton, Ontario L8V 1C3, Canada
Ottawa Hospital - General Campus
Ottawa, Ontario K1H8L6, Canada
Sunnybrook Health Sciences Centre
Toronto, Ontario M4N 3M5, Canada
Princess Margaret Cancer Center - University Health Network
Toronto, Ontario M5G 2M9, Canada
Centre Intégré Universitaire de Santé et de Services Sociaux (CIUSSS) de l'Est-de-l'Ile-de-Montréal - Hôpital Maisonneuve Rosemont
Montréal, Quebec H1T 2M4, Canada
FN Ostrava
Ostrava, Poruba 708 00, Czechia
University Hospital Brno
Brno, 62500, Czechia
Fakultni Nemocnice Kralovske Vinohrady FNKV
Praha 10, Česká Republika 10034, Czechia
Centre de lutte contre le Cancer Leon Berard
Lyon, Rhone 69008, France
Hospital Emile Muller
Mulhouse, 68100, France
Universitaetsklinikum Freiburg
Freiburg im Breisgau, Baden 79106, Germany
Philipps-Universität Marburg, Klinik für Innere medizin, Hämatologie, Onkologie und Immunologie
Marburg, Hesse 35033, Germany
UNIVERSITTSKLINIKUM Schleswig-Holstein
Lubeck, Schleswig-Holstein 23538, Germany
Staedtisches Klinikum Braunschweig
Braunschweig, 38114, Germany
Oberärztin für Innere Medizin, Hämato-/Onkologie und Palliativmedizin
Düsseldorf, 40479, Germany
University Hospital Halle
Halle, 06120, Germany
University of Leipzig
Leisnig, 04103, Germany
Debreceni Egyetem Klinikai Kozpont
Debrecen, 4032, Hungary
Somogy Megyei KAposi Mor Oktato Korhaz
Kaposvár, 7400, Hungary
University of Pecs, 1st Department of Internal Medicine
Pecs, 7400, Hungary
University of Szeged
Szeged, 6725, Hungary
Azienda Ospedaliera Nazionale SS. Antonio e Biagio e C. Arrigo
Alessandria, 15121, Italy
AOUC Azienda Ospedaliero-Universitaria Careggi
Firenze, 50134, Italy
Fondazione IRCCS C Granda OM Policlinico
Milan, 20122, Italy
Azienda Ospedaliero-Universitaria Maggiore della Carità Novara
Novara, 28100, Italy
Ospedale S. Eugenio
Rome, 00144, Italy
ULSS 8 Vicenza - Ospedale San Bortolo di Vicenza
Vicenza, 36100, Italy
Hospital Universitario Central de Asturias
Oviedo, Asturias 33011, Spain
Hospital U. Marqués de Valdecilla
Santander, Cantabria 39008, Spain
Hospital San Pedro de Alcantara
Cáceres, 10003, Spain
Hospital Universitario Virgen de las Nieves
Granada, 18012, Spain
Hospital Duran i Reynals
L'Hospitalet De Llobregat, 08909, Spain
Hospital General Universitario Gregorio Marañón
Madrid, 28007, Spain
Clinica Universitaria Navarra
Madrid, 28027, Spain
Hospital Universitario 12 de Octubre
Madrid, 28041, Spain
Clinica Universitaria Navarra
Pamplona, 31008, Spain
Hospital Universitario de Salamanca
Salamanca, 37007, Spain
Hospital Universitari I Politècnic La Fe
València, 46026, Spain
Oxford University Hopsitals NHS Trust
Oxford, Oxfordshire OX3 7LE, United Kingdom
The Christie NHS Fundation Trust
Manchester, M20 4BX, United Kingdom

References and documents

Study documents

Study protocol · Jan 20, 2021
Statistical analysis plan · Feb 27, 2019
Statistical analysis plan · Oct 15, 2021

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

Registry details

Key details

Study ID: NCT03306264
Lead sponsor: Astex Pharmaceuticals, Inc.
Responsible party: Sponsor
First posted: Oct 11, 2017
Start date: Feb 15, 2018
Primary completion: Sep 10, 2021
Completion: May 25, 2023
Results posted: Jul 1, 2024
Last update: Aug 27, 2024

Oversight

Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

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Study of ASTX727 vs IV Decitabine in Participants With MDS, CMML, and AML

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