A Phase 3 interventional study of SGI-110 (guadecitabine) and Treatment Choice in Leukemia, Myeloid, Acute, sponsored by Astex Pharmaceuticals, Inc.. Completed at 135 sites in 24 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
To compare efficacy and safety between SGI-110 and Treatment Choice in adults with previously untreated AML who are not considered candidates for intensive remission induction chemotherapy.
Cytologically or histologically confirmed diagnosis of AML (except M3 acute promyelocytic leukemia) according to World Health Organization (WHO) classification.
Performance status (ECOG) of 0-3. Adults with previously untreated AML except for hydroxyurea or corticosteroids. Prior hydroxyurea or lenalidomide treatment for myelodysplastic syndrome (MDS) is allowed.
Not considered candidates for intensive remission induction chemotherapy at time of enrollment based on EITHER:
i. Poor performance status (ECOG) score of 2-3.
ii. Clinically significant heart or lung comorbidities, as reflected by at least 1 of:
iii. Liver transaminases >3 × upper limit of normal (ULN).
iv. Other contraindication(s) to anthracycline therapy (must be documented).
v. Other comorbidity the investigator judges incompatible with intensive remission induction chemotherapy, which must be documented and approved by the study medical monitor before randomization.
Creatinine clearance as estimated by the Cockcroft-Gault (C-G) or other medically acceptable formulas ≥30 mL/min.
Exclusion Criteria:
Candidate for intensive remission induction chemotherapy at the time of enrollment.
Candidate for best supportive care only, ie, not a candidate for any active therapy with the TC comparators.
Known extramedullary central nervous system (CNS) AML.
Second malignancy currently requiring active therapy except breast or prostate cancer stable on or responding to endocrine therapy.
Prior treatment with decitabine or azacitidine.
Hypersensitivity to decitabine, SGI-110, or SGI-110 excipients.
Known active human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infection. Inactive hepatitis carrier status or low viral hepatitis titer on antivirals is allowed.
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.
Refractory congestive heart failure unresponsive to medical treatment; active infection resistant to all antibiotics; or advanced pulmonary disease requiring >2 liters per minute (LPM) oxygen.
Guadecitabine 60 mg/m\^2 administered subcutaneously (SC) daily for 5 days (Days 1-5) in 28-day cycles.
Drug: SGI-110 (guadecitabine)
One of the following treatment regimens: 20 mg cytarabine administered subcutaneously (SC) twice daily (BID) on Days 1-10 every 28 days; 20 mg/m\^2 decitabine given as a 1-hour intravenous (IV) infusion daily on Days 1-5 every 28 days; or 75 mg/m\^2 azacitidine given IV or SC daily on Days 1-7 every 28 days.
Drug: Treatment Choice
Investigational medicinal product
Choice of one: cytarabine, decitabine, or azacitidine
Number of Participants With a Complete Response (CR)
Number of participants with a best response of CR assessed based on International Working Group 2003 acute myeloid leukemia (AML) response criteria by a blinded independent pathologist.
Time frame: Up to 38 months (median follow-up of 25.5 months)
Overall Survival
Survival time was defined as the number of days from the day the participant was randomly assigned to study treatment to the date of death, regardless of cause.
Time frame: At 676 death events (up to 38 months)
Number of Participants With Composite CR (CRc)
CRc is reported as the number of participants with a best response of CR, complete response with incomplete platelet recovery (CRp), or complete response with incomplete blood count recovery (CRi).
Time frame: Up to 38 months (median follow-up of 25.5 months)
Number of Days Alive and Out of the Hospital
The date of each hospital admission and discharge was collected for each participant for up to 6 months, unless the participant died or withdrew consent prior to that time. Duration of each hospital stay in days was calculated as date of discharge minus date of admission. The Number of Days Alive and Out of the Hospital (NDAOH) was calculated as: NDAOH=180 - total duration of all hospital stays within 180 days from the first treatment - number of death days before Day 180. For subjects who were lost to follow-up within 6 months, the NDAOH was calculated conservatively assuming that the subject would have died the day after the last contact day.
Time frame: Month 6
Progression-free Survival (PFS)
Progression-free survival was defined as the number of days from randomization to the earliest date of investigator's assessment of disease progression, participant receiving an alternative anti-leukemia therapy (including hematopoietic cell transplant), or relapse by peripheral blood (PB) assessment or blinded bone marrow (BM) assessment, whichever occurred first, or death, regardless of cause.
Time frame: Up to 38 months (median follow-up of 25.5 months)
Number of Red Blood Cell or Platelet Transfusions
The total number of red blood cells (RBCs) transfused or, separately, the total number of platelets transfused up to the 6-month time point for each participant was counted from the date of randomization to Day 180, the date of last contact, or date of death, whichever occurred earlier. One RBC or platelet transfusion was defined as one unit, and a single bag of RBCs or platelets was considered one unit.
Time frame: Month 6
Change in Health-related Quality of Life (QOL) Scores From Baseline: EQ-5D-5L
EuroQol 5-level 5-dimension (EQ-5D-5L) descriptive scores were collected for each participant for a minimum of 6 months, unless the participant died or withdrew consent. Scores within each dimension for EQ-5D (mobility, self-care, usual activity, pain/discomfort, anxiety/depression) were calculated using counts and proportions. Mean change in scores from baseline are summarized in which an index score of 0 represents the worst health state and 1 represents the best health state.
Time frame: Baseline to Month 6
Change in Health-related Quality of Life (QOL) Scores From Baseline: EQ-VAS
EuroQol-Visual Analogue Scale (EQ-VAS) descriptive scores were collected for each participant for a minimum of 6 months, unless the participant died or withdrew consent. A vertical 20-cm scale for EQ-VAS was used where the lowest value of 0 was labeled "the worst health you can imagine" and the top value of 100 was labeled "the best health you can imagine." Mean change in scores from baseline are summarized.
Time frame: Baseline to Month 6
Duration of CR
Duration of CR (in number of days) was calculated from the first time a CR was observed to the time of relapse, defined as the earliest time point whereby BM assessment or PB assessment indicated relapse/disease progression due to reappearance of leukemic blasts in PB or ≥ 5% leukemic blasts in BM.
Time frame: Up to 38 months (median follow-up of 25.5 months)
A total of 949 participants were assessed for inclusion in the study. Of these, 134 participants failed screening assessments and 815 participants were randomized.
| Milestone | SGI-110 (Guadecitabine) | Treatment Choice |
|---|---|---|
| Started | 408 | 407 |
| Completed | 55 | 40 |
| Not completed | 353 | 367 |
| Withdrew: Death | 336 | 335 |
| Withdrew: Withdrawal by subject | 14 | 27 |
| Withdrew: Lost to follow-up | 3 | 5 |
Number of participants with a best response of CR assessed based on International Working Group 2003 acute myeloid leukemia (AML) response criteria by a blinded independent pathologist.
| Participants | SGI-110 (Guadecitabine) | Treatment Choice |
|---|---|---|
| Number of Participants With a Complete Response (CR) | 79 | 71 |
Survival time was defined as the number of days from the day the participant was randomly assigned to study treatment to the date of death, regardless of cause.
| days | SGI-110 (Guadecitabine) | Treatment Choice |
|---|---|---|
| Overall Survival | 213 (187 to 255) | 254 (223 to 282) |
CRc is reported as the number of participants with a best response of CR, complete response with incomplete platelet recovery (CRp), or complete response with incomplete blood count recovery (CRi).
| Participants | SGI-110 (Guadecitabine) | Treatment Choice |
|---|---|---|
| Number of Participants With Composite CR (CRc) | 93 | 91 |
The date of each hospital admission and discharge was collected for each participant for up to 6 months, unless the participant died or withdrew consent prior to that time. Duration of each hospital stay in days was calculated as date of discharge minus date of admission. The Number of Days Alive and Out of the Hospital (NDAOH) was calculated as: NDAOH=180 - total duration of all hospital stays within 180 days from the first treatment - number of death days before Day 180. For subjects who were lost to follow-up within 6 months, the NDAOH was calculated conservatively assuming that the subject would have died the day after the last contact day.
| days | SGI-110 (Guadecitabine) | Treatment Choice |
|---|---|---|
| Number of Days Alive and Out of the Hospital | 98.1 ± 63.6 | 105.7 ± 63.58 |
Progression-free survival was defined as the number of days from randomization to the earliest date of investigator's assessment of disease progression, participant receiving an alternative anti-leukemia therapy (including hematopoietic cell transplant), or relapse by peripheral blood (PB) assessment or blinded bone marrow (BM) assessment, whichever occurred first, or death, regardless of cause.
| days | SGI-110 (Guadecitabine) | Treatment Choice |
|---|---|---|
| Progression-free Survival (PFS) | 159 (136 to 178) | 166 (148 to 179) |
The total number of red blood cells (RBCs) transfused or, separately, the total number of platelets transfused up to the 6-month time point for each participant was counted from the date of randomization to Day 180, the date of last contact, or date of death, whichever occurred earlier. One RBC or platelet transfusion was defined as one unit, and a single bag of RBCs or platelets was considered one unit.
| transfusion units | SGI-110 (Guadecitabine) | Treatment Choice |
|---|---|---|
| Red Blood Cell Transfusions | 16.2 ± 11.84 | 15.6 ± 13.02 |
| Platelet Transfusions | 12.5 ± 18.78 | 14.4 ± 39.10 |
EuroQol 5-level 5-dimension (EQ-5D-5L) descriptive scores were collected for each participant for a minimum of 6 months, unless the participant died or withdrew consent. Scores within each dimension for EQ-5D (mobility, self-care, usual activity, pain/discomfort, anxiety/depression) were calculated using counts and proportions. Mean change in scores from baseline are summarized in which an index score of 0 represents the worst health state and 1 represents the best health state.
| score on a scale | SGI-110 (Guadecitabine) | Treatment Choice |
|---|---|---|
| Baseline | 0.7767 ± 0.2160 | 0.7663 ± 0.2291 |
| Month 6 | 0.8252 ± 0.1825 | 0.8240 ± 0.1948 |
| Change from Baseline | -0.0023 ± 0.1830 | 0.0112 ± 0.2325 |
EuroQol-Visual Analogue Scale (EQ-VAS) descriptive scores were collected for each participant for a minimum of 6 months, unless the participant died or withdrew consent. A vertical 20-cm scale for EQ-VAS was used where the lowest value of 0 was labeled "the worst health you can imagine" and the top value of 100 was labeled "the best health you can imagine." Mean change in scores from baseline are summarized.
| score on a scale | SGI-110 (Guadecitabine) | Treatment Choice |
|---|---|---|
| Baseline | 64.64 ± 21.69 | 63.58 ± 21.05 |
| Month 6 | 72.76 ± 18.61 | 71.72 ± 18.88 |
| Change from Baseline | 3.28 ± 19.35 | 3.67 ± 22.16 |
Duration of CR (in number of days) was calculated from the first time a CR was observed to the time of relapse, defined as the earliest time point whereby BM assessment or PB assessment indicated relapse/disease progression due to reappearance of leukemic blasts in PB or ≥ 5% leukemic blasts in BM.
| days | SGI-110 (Guadecitabine) | Treatment Choice |
|---|---|---|
| Duration of CR | 217 (175 to 261) | 231 (182 to 289) |
Collected over Up to 51 months. Median (range) duration of treatment was 5 cycles (1-42) for SGI-110 and 5 cycles (1-37) for Treatment Choice (28 days per cycle). Treatment-emergent adverse events were events that first occurred or worsened after the first dose of study treatment until 30 days after the last dose or start of an alternative anti-leukemia treatment, whichever occurred first.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| SGI-110 (Guadecitabine) | 341/408 (83.6%) | 327/401 (81.5%) | 379/401 (94.5%) |
| Treatment Choice | 344/407 (84.5%) | 297/392 (75.8%) | 371/392 (94.6%) |
| Event | SGI-110 (Guadecitabine) | Treatment Choice |
|---|---|---|
| PneumoniaInfections and infestations | 117/401 | 79/392 |
| Febrile neutropeniaBlood and lymphatic system disorders | 101/401 | 88/392 |
| SepsisInfections and infestations | 62/401 | 44/392 |
| Septic shockInfections and infestations | 16/401 | 17/392 |
| PyrexiaGeneral disorders | 16/401 | 13/392 |
| Acute kidney injuryRenal and urinary disorders | 11/401 | 15/392 |
| ThrombocytopeniaBlood and lymphatic system disorders | 15/401 | 5/392 |
| Urinary tract infectionInfections and infestations | 14/401 | 10/392 |
| Cardiac failureCardiac disorders | 8/401 | 10/392 |
| General physical health deteriorationGeneral disorders | 9/401 | 10/392 |
| Event | SGI-110 (Guadecitabine) | Treatment Choice |
|---|---|---|
| ConstipationGastrointestinal disorders | 125/401 | 114/392 |
| DiarrheaGastrointestinal disorders | 122/401 | 83/392 |
| ThrombocytopeniaBlood and lymphatic system disorders | 116/401 | 101/392 |
| NeutropeniaBlood and lymphatic system disorders | 115/401 | 88/392 |
| PyrexiaGeneral disorders | 89/401 | 110/392 |
| NauseaGastrointestinal disorders | 91/401 | 108/392 |
| HypokalemiaMetabolism and nutrition disorders | 96/401 | 77/392 |
| Edema peripheralGeneral disorders | 95/401 | 78/392 |
| Decreased appetiteMetabolism and nutrition disorders | 89/401 | 62/392 |
| AnemiaBlood and lymphatic system disorders | 88/401 | 78/392 |
All randomized participants
| Age, Continuous(years) | SGI-110 (Guadecitabine) | Treatment Choice | Total |
|---|---|---|---|
| Mean | 75.9 ± 6.2 | 75.9 ± 5.8 | 75.9 ± 6.0 |
| Sex: Female, Male(Participants) | SGI-110 (Guadecitabine) | Treatment Choice | Total |
|---|---|---|---|
| Female | 177 | 165 | 342 |
| Male | 231 | 242 | 473 |
| Ethnicity (NIH/OMB)(Participants) | SGI-110 (Guadecitabine) | Treatment Choice | Total |
|---|---|---|---|
| Hispanic or Latino | 15 | 14 | 29 |
| Not Hispanic or Latino | 365 | 345 | 710 |
| Unknown or Not Reported | 28 | 48 | 76 |
| Race (NIH/OMB)(Participants) | SGI-110 (Guadecitabine) | Treatment Choice | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 1 | 1 |
| Asian | 71 | 74 | 145 |
| Native Hawaiian or Other Pacific Islander | 2 | 0 | 2 |
| Black or African American | 9 | 5 | 14 |
| White | 311 | 291 | 602 |
| More than one race | 0 | 1 | 1 |
| Unknown or Not Reported | 15 | 35 | 50 |
Showing the first 100 of 135 sites across 24 countries.
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Astex Pharmaceuticals, Inc.