Phase 3 Randomized, Open-Label Study of Guadecitabine vs Treatment Choice in Previously Treated Acute Myeloid Leukemia

Browse trials for

• Leukemia 5,446
• Leukemia, Myeloid 2,450
• Leukemia, Myeloid, Acute 2,968

Keywords

• AML, acute myeloid leukemia, guadecitabine, SGI-110, Phase 3

Study arms

• Experimental
  guadecitabine

  Guadecitabine will be given SC at a dose of 60 mg/m\^2 in 28-day cycles (delayed as necessary to allow blood count recovery).

  Drug: guadecitabine

• Active comparator
  Treatment Choice (TC)

  1. High intensity 2. Low intensity 3. Best supportive care (BSC).

  Drug: Treatment Choice (TC)

Interventions

• Drugguadecitabine

  In Cycle 1, guadecitabine will be given for 10 days on Days 1-5 and Days 8-12. In Cycle 2, the guadecitabine dose will be 60 mg/m\^2 for either 10 days (Days 1-5 and 8-12) or 5 days (Days 1-5 only) based on assessment of disease response, and hematological recovery by Day ≥28.

  Also known as: SGI-110

• DrugTreatment Choice (TC)

  * High intensity: intermediate or high dose cytarabine (HiDAC); mitoxantrone, etoposide, and cytarabine (MEC); or fludarabine, cytarabine, G-CSF, +/- idarubicin (FLAG/FLAG-Ida). * Low intensity: low dose cytarabine (LDAC), decitabine, or azacitidine. * Best Supportive Care (BSC).

Primary outcomes

1. Overall Survival

   Overall survival is defined as number of days from day of randomization to date of death, regardless of cause.

   Time frame: From the date of randomization until the date of death, or approximately 34 months

Secondary outcomes

1. Event-Free Survival

   Event-free survival is defined as number of days from randomization to earliest date of treatment discontinuation (for reasons other than initiation of hematopoietic cell transplant \[HCT\]), start of alternative anti-leukemia therapy (except HCT), or death.

   Time frame: From the date of randomization until the date of death, or approximately 38 months

2. Long-Term Survival

   Survival rate at 1 year after randomization; participants were also followed to estimate 2-year survival rate.

   Time frame: Up to approximately 38 months

3. Number of Days Alive and Out of the Hospital (NDAOH)

   Number of days participants alive and out of hospital during first 6 months of the study.

   Time frame: 6 months

4. Transfusion Independence Rate

   Number of participants without red blood cells (RBC) or platelet transfusion for any 8-week period after treatment divided by total number of participants in efficacy analysis.

   Time frame: Baseline up to approximately 38 months

5. Complete Response Rate

   The Complete response (CR) rate based on modified International Working Group (IWG) 2003 AML Response Criteria was calculated as the number of participants with a best response of CR divided by the total number of participants included in the efficacy analysis. CR as per modified 2003 IWG AML Response Criteria is absolute neutrophil count (ANC) ≥1000/μL, platelets ≥100,000/μL, independence from red blood cells (RBC) and platelet transfusions over the past week, no leukemic blasts in peripheral blood and bone marrow should contain less than 5% blast cells.

   Time frame: Baseline to end of treatment, or approximately 38 months

6. Combined Complete Response and Complete Response With Partial Hematologic Recovery Rate

   The combined CR and CR with partial hematologic recovery rate based on modified International Working Group (IWG) 2003 AML Response Criteria was calculated as number of participants with CR and CR with partial hematologic recovery divided by the total number of participants included in the efficacy analysis. CR as per modified 2003 IWG AML Response Criteria is absolute neutrophil count (ANC) ≥1000/μL, platelets ≥100,000/μL, independence from red blood cells (RBC) and platelet transfusions over the past week, no leukemic blasts in peripheral blood and bone marrow should contain less than 5% blast cells.

   Time frame: Baseline to end of treatment, or approximately 38 months

7. Composite Complete Response Rate

   Composite complete response rate based on modified IWG 2003 AML Response Criteria defined as number of participants with best response of CR, CR with incomplete platelet recovery (CRp), or CR with incomplete blood count recovery (CRi) divided by total number of participants in efficacy analysis. CR as per modified 2003 IWG AML Response Criteria is ANC ≥1000/μL, platelets ≥100,000/μL, independence from RBC and platelet transfusions over the past week, no leukemic blasts in peripheral blood and bone marrow should contain less than 5% blast cells. CRp is defined as ANC ≥1000/μL, Platelets \<100,000/μL, independence from RBC transfusions over the past week, no leukemic blasts and bone marrow should contain less than 5% blast cells. CRi is defined as ANC \<1000/μL, no leukemic blasts and bone marrow should contain less than 5% blast cells.

   Time frame: Baseline to end of treatment, or approximately 38 months

8. Hematopoietic Cell Transplant (HCT) Rate

   Number of participants who received HCT after randomization divided by total number of participants in efficacy analysis.

   Time frame: Baseline to long term follow-up or approximately 38 months

9. Duration of Complete Response (CR) + CR With Partial Hematologic Recovery (CRh)

   The time from first CR or CRh to time of relapse (the date of the earliest of the following 3 events): 1. relapse (defined as the earliest time point whereby BM assessment or PB assessment by the investigator indicate relapse/disease progression due to confirmed reappearance of leukemic blasts in PB or ≥5% leukemic blasts in BM, or clinical progression determined by the investigator), 2. start of alternative therapy (except HCT) or 3. death.

   Time frame: Baseline to end of treatment, or approximately 38 months

10. Change From Baseline in EuroQoL-5 Dimension 5 Level (EQ-5D-5L) Index Scores

    Index score is calculated based on 5-level version of the EQ-5D descriptive system using the value set for England. The range of index score is from -0.281 (for the worst health state, score of 5 for all categories) to 1 (for the best health state, score of 1 for all categories).

    Time frame: Baseline to 6 months

11. Change in EQ-5D-5L Visual Analogue Scale (VAS) Score

    VAS score is obtained using vertical 20-cm visual analogue scale with the top value of 100 labelled as 'the best health you can imagine' and the bottom value of 0 labelled as 'the worst health you can imagine'.

    Time frame: Baseline to 6 months

12. Percentage of Participants With Adverse Events (AEs)

    An AE is any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can therefore be any unfavorable and unintended sign (including a clinically significant abnormal finding in laboratory tests or other diagnostic procedures), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.

    Time frame: From first dose until 30 days after the last dose of study drug, or approximately 38 months

13. All-Cause Mortality

    All-cause mortality in the first 30 days and first 60 days after the start of treatment divided by the total number of participants receiving at least one dose of study treatment.

    Time frame: From the first dose until 60 days after the first dose of study drug

Baseline characteristics

Study documents

• Study protocol · Oct 29, 2018
• Statistical analysis plan · Jul 22, 2020

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

Individual participant data

Plan to share: No