NCT05079230终止3 期
A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Magrolimab Versus Placebo in Combination With Venetoclax and Azacitidine in Newly Diagnosed, Previously Untreated Patients With Acute Myeloid Leukemia Who Are Ineligible for Intensive Chemotherapy
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 378
- 试验地点
- 164
- 主要终点
- Overall Survival (OS)
研究概览
简要总结
The goal of this clinical study is to compare the study drugs, magrolimab + venetoclax + azacitidine, versus placebo + venetoclax + azacitidine in participants with untreated acute myeloid leukemia (AML) who are not able to have chemotherapy.
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
- Double (Participant, Investigator)
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
- •Previously untreated individuals with histological confirmation of acute myeloid leukemia (AML) by World Health Organization (WHO) criteria who are ineligible for treatment with a standard cytarabine and anthracycline induction regimen due to age, or comorbidity. Individuals must be considered ineligible for intensive chemotherapy, defined by the following:
- •≥ 75 years of age; Or
- •≥ 18 to 74 years of age with at least 1 of the following comorbidities:
- •Eastern Cooperative Oncology Group (ECOG) performance status of 2 or 3
- •Diffusing capacity of the lung of carbon monoxide ≤ 65% or forced expiratory volume in 1 second ≤ 65%
- •Left ventricular ejection fraction ≤ 50%
- •Baseline creatinine clearance ≥ 30 mL/min to < 45 mL/min calculated by the Cockcroft Gault formula or measured by 24-hour urine collection
- •Hepatic disorder with total bilirubin > 1.5 x upper limit of normal (ULN)
- •Any other comorbidity that the investigator judges to be incompatible with intensive chemotherapy
- •ECOG performance status:
- •Of 0 to 2 for individuals ≥ 75 years of age Or
- •Of 0 to 3 for individuals ≥ 18 to 74 years of age
- •Individuals with white blood cell (WBC) count ≤ 20 x 10^3/μL prior to randomization. If the individual's WBC is > 20 x10^3/μL prior to randomization, the individual can be enrolled, assuming all other eligibility criteria are met. However, the WBC should be ≤ 20 x 10^3/μL prior to the first dose of study treatment and prior to each magrolimab/placebo dose during Cycle
- •Note: Individuals can be treated with hydroxyurea and/or leukapheresis prior to randomization and throughout the study to reduce the WBC to ≤ 20 x 10^3/μL to enable eligibility for study drug dosing
- •Hemoglobin must be ≥ 9 g/dL prior to initial dose of study treatment
- •Note: Transfusions are allowed to meet hemoglobin eligibility
- •Pretreatment blood cross-match completed
排除标准
- •Prior treatment with any of the following:
- •cluster of differentiation 47 (CD47) or signal regulatory protein alpha (SIRPα)-targeting agents
- •Antileukemic therapy for the treatment of AML (eg, hypomethylating agents (HMAs), low-dose cytarabine, and/or venetoclax), excluding hydroxyurea
- •Note: Individuals with prior MDS who have not received prior HMAs or venetoclax or chemotherapeutic agents for MDS may be enrolled in the study. Prior treatment with myelodysplastic syndrome (MDS) therapies including, but not limited to lenalidomide, erythroid-stimulating agents, or similar red blood cell negative (RBC-), white blood cell negative (WBC-), or platelet-direct therapies or growth factors is allowed for these individuals.
- •Clinical suspicion of or documented active central nervous system (CNS) involvement with AML
- •Individuals who have acute promyelocytic leukemia
- •Second malignancy, except MDS, treated basal cell or localized squamous skin carcinomas, localized prostate cancer, or other malignancies for which individuals are not on active anticancer therapies and have had no evidence of active malignancy for at least 1 year
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Magrolimab + Venetoclax + Azacitidine
Experimental
Participants will receive
- magrolimab: 1 mg/kg priming dose on Days 1 and 4; 15 mg/kg on Day 8; and 30 mg/kg on Days 11, 15, and then every week for 5 doses and every 2 weeks thereafter
- venetoclax: 100 mg on Cycle 1 Day 1, 200 mg on Cycle 1 Day 2, 400 mg on Cycle 1 Day 3 and daily thereafter
- azacitidine: 75 mg/m^2 on Days 1-7 or Days 1-5 and 8-9 of each cycle
Each cycle is 28 days.
干预措施: Magrolimab (Drug)
Magrolimab + Venetoclax + Azacitidine
Experimental
Participants will receive
- magrolimab: 1 mg/kg priming dose on Days 1 and 4; 15 mg/kg on Day 8; and 30 mg/kg on Days 11, 15, and then every week for 5 doses and every 2 weeks thereafter
- venetoclax: 100 mg on Cycle 1 Day 1, 200 mg on Cycle 1 Day 2, 400 mg on Cycle 1 Day 3 and daily thereafter
- azacitidine: 75 mg/m^2 on Days 1-7 or Days 1-5 and 8-9 of each cycle
Each cycle is 28 days.
干预措施: Venetoclax (Drug)
Magrolimab + Venetoclax + Azacitidine
Experimental
Participants will receive
- magrolimab: 1 mg/kg priming dose on Days 1 and 4; 15 mg/kg on Day 8; and 30 mg/kg on Days 11, 15, and then every week for 5 doses and every 2 weeks thereafter
- venetoclax: 100 mg on Cycle 1 Day 1, 200 mg on Cycle 1 Day 2, 400 mg on Cycle 1 Day 3 and daily thereafter
- azacitidine: 75 mg/m^2 on Days 1-7 or Days 1-5 and 8-9 of each cycle
Each cycle is 28 days.
干预措施: Azacitidine (Drug)
Magrolimab Matching Placebo + Venetoclax + Azacitidine
Placebo Comparator
Participants will receive
- magrolimab matching placebo: Days 1, 4, 8, 11, and 15, then every week for 5 doses and every 2 weeks thereafter
- venetoclax: 100 mg on Cycle 1 Day 1, 200 mg on Cycle 1 Day 2, 400 mg on Cycle 1 Day 3 and daily thereafter
- azacitidine: 75 mg/m^2 on Days 1-7 or Days 1-5 and 8-9 of each cycle
Each cycle is 28 days.
干预措施: Venetoclax (Drug)
Magrolimab Matching Placebo + Venetoclax + Azacitidine
Placebo Comparator
Participants will receive
- magrolimab matching placebo: Days 1, 4, 8, 11, and 15, then every week for 5 doses and every 2 weeks thereafter
- venetoclax: 100 mg on Cycle 1 Day 1, 200 mg on Cycle 1 Day 2, 400 mg on Cycle 1 Day 3 and daily thereafter
- azacitidine: 75 mg/m^2 on Days 1-7 or Days 1-5 and 8-9 of each cycle
Each cycle is 28 days.
干预措施: Azacitidine (Drug)
Magrolimab Matching Placebo + Venetoclax + Azacitidine
Placebo Comparator
Participants will receive
- magrolimab matching placebo: Days 1, 4, 8, 11, and 15, then every week for 5 doses and every 2 weeks thereafter
- venetoclax: 100 mg on Cycle 1 Day 1, 200 mg on Cycle 1 Day 2, 400 mg on Cycle 1 Day 3 and daily thereafter
- azacitidine: 75 mg/m^2 on Days 1-7 or Days 1-5 and 8-9 of each cycle
Each cycle is 28 days.
干预措施: Placebo (Drug)
结局指标
主要结局
Overall Survival (OS)
时间窗: Up to 1.6 years
OS was measured from the date of randomization to the date of death from any cause. Participants were censored at last known alive date. Kaplan-Meier (KM) estimates were used in outcome measure analysis.
次要结局
- Rate of Complete Remission (CR)(Up to 1.6 years)
- Rate of Complete Remission (CR) + Complete Remission With Partial Hematologic Recovery (CRh)(Up to 1.6 years)
- Event-Free Survival (EFS)(Up to 1.6 years)
- Duration of CR + CRh in Participants Who Achieved Complete Remission (CR) or Complete Remission With Partial Hematologic Recovery (CRh)(Up to 1.6 years)
- Platelet Transfusion Independence Conversion Rate(Up to 1.6 years)
- Duration of Complete Remission (DCR) in Participants Who Achieved Complete Remission (CR)(Up to 1.6 years)
- Red Blood Cell (RBC) Transfusion Independence Conversion Rate(Up to 1.6 years)
- Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)(First dose date up to 1.4 years plus 70 days)
- Percentage of Participants With Anti-Magrolimab Antibodies(Up to 1.6 years)
- Maximum Levels of Serum Anti-Magrolimab Antibodies(Up to 1.6 years)
- Rate of CR Without Minimal Residual Disease (CRMRD-)(Up to 1.6 years)
- Rate of CR/CRh Without Minimal Residual Disease (CR/CRhMRD-)(Up to 1.6 years)
- Time to First Deterioration (TTD) on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Global Health Status/Quality of Life (GHS/QoL) Scale(Up to 1.6 years)
- Time to First Deterioration (TTD) on the EORTC QLQ-C30 Physical Functioning Scale(Up to 1.6 years)
- Percentage of Participants Experiencing Grade 3 or Higher Treatment-Emergent Laboratory Abnormalities(First dose date up to 1.4 years, plus 70 days)
- Serum Concentration of Magrolimab Over Time(Predose on Day 1, Day 8, Day 15, Day 29; Predose on Day 57 and 1 hour post-dose; Predose on Day 113, Day 169, Day 253, and Day 337.)
研究者
研究点 (164)
Loading locations...
相似试验
终止
3 期
A Study Evaluating Safety and Efficacy of Venetoclax in Combination With Azacitidine Versus Standard of Care After Allogeneic Stem Cell Transplantation (SCT) in Participants With Acute Myeloid Leukemia (AML)Acute Myeloid Leukemia (AML)CancerNCT04161885AbbVie465
终止
3 期
Study of Magrolimab in Combination With Azacitidine Versus Physician's Choice of Venetoclax in Combination With Azacitidine or Intensive Chemotherapy in Patients With TP53 Mutant Acute Myeloid Leukemia That Have Not Been TreatedAcute Myeloid LeukemiaNCT04778397Gilead Sciences258
招募中
2 期
AZA + Venetoclax as Maintenance Therapy in Younger Adults With AML in First RemissionAcute Myeloid Leukemia (AML) in RemissionNCT05404906The First Affiliated Hospital of Soochow University124
招募中
3 期
A Study to Evaluate Axatilimab and Corticosteroids as Initial Treatment for Chronic Graft-Versus-Host DiseaseChronic Graft-versus-host-diseaseNCT06585774Incyte Corporation240
进行中（未招募）
2 期
Venetoclax + Azacitidine vs. Induction Chemotherapy in AMLAcute Myeloid LeukemiaNCT04801797Massachusetts General Hospital172