A Phase 3, Multicenter, Randomized, Open-Label Study of Guadecitabine (SGI-110) Versus Treatment Choice in Adults With Previously Treated Acute Myeloid Leukemia
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 302
- 试验地点
- 95
- 主要终点
- Overall Survival
研究概览
简要总结
Multicenter, randomized, open-label, parallel-group study of guadecitabine vs treatment choice (TC). Participants 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).
- BSC.
详细描述
This Phase 3, randomized, open-label, parallel-group multicenter study of the efficacy and safety of guadecitabine in adults with previously treated acute myeloid leukemia (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 participant participation will vary, and participants may continue to receive treatment for as long as they continue to benefit.
Approximately 404 participants from approximately 100 study centers will be randomly assigned to either guadecitabine or treatment choice (TC) in a 1:1 ratio (approximately 202 participants 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 subcutaneous (SC) at a dose of 60 microgram per meter square (mg/m^2) 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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult participants ≥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-
- •Participants 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.
- •Participants 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.
排除标准
- •Known clinically active central nervous system (CNS) or extramedullary AML, except leukemia cutis.
- •Participants 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 participants 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 participant 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 participant at an imminent risk of death.
- •Participants with high PB blasts >50% AND poor ECOG PS of 2.
研究组 & 干预措施
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).
干预措施: guadecitabine (Drug)
Treatment Choice (TC)
- High intensity
- Low intensity
- Best supportive care (BSC).
干预措施: Treatment Choice (TC) (Drug)
结局指标
主要结局
Overall Survival
时间窗: From the date of randomization until the date of death, or approximately 34 months
Overall survival is defined as number of days from day of randomization to date of death, regardless of cause.
次要结局
- Number of Days Alive and Out of the Hospital (NDAOH)(6 months)
- Event-Free Survival(From the date of randomization until the date of death, or approximately 38 months)
- Long-Term Survival(Up to approximately 38 months)
- Transfusion Independence Rate(Baseline up to approximately 38 months)
- Composite Complete Response Rate(Baseline to end of treatment, or approximately 38 months)
- Complete Response Rate(Baseline to end of treatment, or approximately 38 months)
- Hematopoietic Cell Transplant (HCT) Rate(Baseline to long term follow-up or approximately 38 months)
- Duration of Complete Response (CR) + CR With Partial Hematologic Recovery (CRh)(Baseline to end of treatment, or approximately 38 months)
- Change From Baseline in EuroQoL-5 Dimension 5 Level (EQ-5D-5L) Index Scores(Baseline to 6 months)
- Change in EQ-5D-5L Visual Analogue Scale (VAS) Score(Baseline to 6 months)
- Percentage of Participants With Adverse Events (AEs)(From first dose until 30 days after the last dose of study drug, or approximately 38 months)
- Combined Complete Response and Complete Response With Partial Hematologic Recovery Rate(Baseline to end of treatment, or approximately 38 months)
- All-Cause Mortality(From the first dose until 60 days after the first dose of study drug)