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 : Completed
First Posted : September 30, 2016
Last Update Posted : September 9, 2021
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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)|
|Actual Enrollment :||302 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|
|Actual Primary Completion Date :||January 20, 2020|
|Actual Study Completion Date :||June 1, 2020|
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.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- Adult subjects ≥18 years of age who are able to understand study procedures, comply with them, and provide written informed consent before any study-specific procedure.
- History of cytologically or histologically confirmed diagnosis of AML (except acute promyelocytic leukemia) according to the 2008 World Health Organization (WHO) classification (bone marrow [BM] or peripheral blood [PB] blast counts ≥20%).
- Performance status (Eastern Cooperative Oncology Group; ECOG) of 0-2.
- Subjects with AML previously treated with initial induction therapy using a standard intensive chemotherapy regimen, including cytarabine and an anthracycline, and who are refractory to initial induction (primary refractory) or in relapse after such initial induction with or without prior HCT.
- Subjects must have either PB or BM blasts ≥5% at time of randomization.
- Creatinine clearance or glomerular filtration rate ≥30 mL/min as estimated by the Cockroft-Gault (C-G) or other medically acceptable formulas, such as MDRD (Modification of Diet in Renal Disease) or CKD-EPI (the Chronic Kidney Disease Epidemiology Collaboration).
- Women of child-bearing potential must not be pregnant or breastfeeding and must have a negative pregnancy test at screening. Women of child-bearing potential and men with female partners of child-bearing potential must agree to practice 2 highly effective contraceptive measures of birth control and must agree not to become pregnant or father a child (a) while receiving treatment of guadecitabine, decitabine, or azacitidine and for at least 3 months after completing treatment and (b) while receiving treatment with high-intensity TC or LDAC and for at least 6 months after completing treatment.
- Known clinically active central nervous system (CNS) or extramedullary AML, except leukemia cutis.
- Subjects who are in first relapse after initial induction, if they had a response duration of >12 months from date when first response first documented or if they are good candidates for HCT.
- BCR-ABL-positive leukemia (chronic myelogenous leukemia in blast crisis).
- Second malignancy currently requiring active therapy, except breast or prostate cancer stable on or responding to endocrine therapy.
- Grade 3 or higher Graft Versus Host Disease (GVHD), or GVHD on either a calcineurin inhibitor or prednisone more than 5 mg/day.
- Prior treatment with guadecitabine for any indication, or more than 2 cycles of prior decitabine or azacitidine.
- Hypersensitivity to decitabine, guadecitabine, or any of their excipients.
- Treated with any investigational therapy within 2 weeks of the first dose of study treatment.
- Total serum bilirubin >2.5 × upper limit of normal (ULN; except for subjects with Gilbert's Syndrome for whom direct bilirubin is <2.5 × ULN), or liver cirrhosis, or chronic liver disease Child-Pugh Class B or C.
- 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 non-AML-associated pulmonary disease requiring >2 liters per minute (LPM) oxygen, or any other condition that puts the subject at an imminent risk of death.
- Subjects with high PB blasts >50% AND poor ECOG PS of 2.
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
|Study Director:||Harold N Keer, MD, PhD||Astex Pharmaceuticals, Inc.|
|Responsible Party:||Astex Pharmaceuticals, Inc.|
|Other Study ID Numbers:||
|First Posted:||September 30, 2016 Key Record Dates|
|Last Update Posted:||September 9, 2021|
|Last Verified:||September 2021|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
AML, acute myeloid leukemia, guadecitabine, SGI-110, Phase 3
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type