Phase 3 Randomized, Open-Label Study of Guadecitabine vs Treatment Choice in Previously Treated Acute Myeloid Leukemia
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|ClinicalTrials.gov Identifier: NCT02920008|
Recruitment Status : Recruiting
First Posted : September 30, 2016
Last Update Posted : July 17, 2018
Multicenter, randomized, open-label, parallel-group study of guadecitabine vs treatment choice (TC). Subjects will be randomly assigned in a 1:1 ratio to either guadecitabine or TC. TC options include the 8 high or low intensity, locally available regimens below; or Best supportive Care (BSC) alone:
- High intensity (intermediate or high dose cytarabine [HiDAC]; mitoxantrone, etoposide, and cytarabine [MEC]; or fludarabine, cytarabine, granulocyte colony stimulating factor [G-CSF], +/- idarubicin [FLAG/FLAG-Ida]).
- Low intensity (low dose cytarabine [LDAC], decitabine, or azacitidine).
|Condition or disease||Intervention/treatment||Phase|
|Acute Myeloid Leukemia||Drug: guadecitabine Drug: Treatment Choice (TC)||Phase 3|
This Phase 3, randomized, open-label, parallel-group multicenter study of the efficacy and safety of guadecitabine in adults with previously treated AML will be conducted in approximately 20 countries. There will be a 14-day screening period, a treatment period, a safety follow-up visit, and a long-term follow-up period. The study is expected to last approximately 2 years. Duration of individual subject participation will vary, and subjects may continue to receive treatment for as long as they continue to benefit.
Approximately 404 subjects from approximately 100 study centers will be randomly assigned to either guadecitabine or treatment choice (TC) in a 1:1 ratio (approximately 202 subjects per group). TC is as follows:
- 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).
Guadecitabine will be given SC at a dose of 60 mg/m2 in 28-day cycles. In Cycle 1, guadecitabine will be given for 10 days on Days 1-5 and Days 8-12. Cycle 2 will be either the 5-day regimen (Days 1-5) or 10-day regimen (Days 1-5 and 8-12) based on assessment of disease response and hematologic recovery at the end of Cycle 1. In subsequent cycles, guadecitabine treatment will be for 5 days only (Days 1-5).
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||404 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 3, Multicenter, Randomized, Open-Label Study of Guadecitabine (SGI-110) Versus Treatment Choice in Adults With Previously Treated Acute Myeloid Leukemia|
|Actual Study Start Date :||March 16, 2017|
|Estimated Primary Completion Date :||April 2019|
|Estimated Study Completion Date :||June 2019|
Guadecitabine will be given SC at a dose of 60 mg/m2 in 28-day cycles (delayed as necessary to allow blood count recovery).
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/m2 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.
Other Name: SGI-110
Active Comparator: Treatment Choice (TC)
Drug: Treatment Choice (TC)
- Overall survival [ Time Frame: 24 months ]Number of days from day subject was randomized to date of death, regardless of cause.
- Event-free survival [ Time Frame: 24 months ]Number of days from randomization to earliest date of disease progression, treatment discontinuation, start of anti-leukemia therapy, or death.
- Long-term survival [ Time Frame: 24 months ]Survival at one year.
- Number of days alive and out of the hospital (NDAOH). [ Time Frame: 24 months ]Number of days subject alive and out of hospital during first 6 months of the study.
- Transfusion independence rate [ Time Frame: 24 months ]Number of subjects without RBC or platelet transfusion for any 8-week period after treatment divided by total number of subjects in efficacy analysis.
- Complete response rate [ Time Frame: 24 months ]Number of subjects with best response of CR divided by total number of subjects in efficacy analysis.
- Composite complete response [ Time Frame: 24 months ]Number of subjects with best response of CR, CRp, or CRi divided by total number of subjects in efficacy analysis.
- Hematopoietic cell transplant (HCT) rate [ Time Frame: 24 months ]Number of subjects who received HCT after randomization divided by total number of subjects in efficacy analysis.
- Duration of complete response (CR) [ Time Frame: 24 months ]Duration of CR (in number of days) will be calculated from the first time a CR is observed to time of relapse (defined as the earliest time point whereby BM assessment or PB assessment indicate relapse/disease progression due to confirmed reappearance of ≥5% leukemic blasts in PB or ≥5% leukemic blasts in BM.
- Quality of life [ Time Frame: 6 months ]The calculation for EQ-5D-5L index value will be performed according to EuroQol group's EQ-5D-5L User Guide.
- Incidence and severity of adverse events [ Time Frame: 24 months ]Subject reported and investigator-observed AEs and 30- and 60-day all-cause mortality, along with clinical laboratory tests (hematology, chemistries), concomitant Medications, physical examination, vital signs, ECOG performance status and ECGs.
- 30- and 60-day all-cause mortality [ Time Frame: 24 months ]Number of deaths, regardless of cause, within 30 or 60 days from the first study dose divided by the total number of subjects included in the safety analysis set.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02920008
|Contact: Laksmi Wilsonemail@example.com|
|Contact: Harold N Keer, MD, PhD||925-560-2914||ASTRALfirstname.lastname@example.org|
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|Study Director:||Harold N Keer, MD, PhD||Astex Pharmaceuticals|