A Phase Ib Trial With Dose Expansion Evaluating CPX-351 Plus Gemtuzumab Ozogamicin for Relapsed Acute Myelogenous Leukemia
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 13
- 试验地点
- 5
- 主要终点
- Maximum tolerated dose (MTD)
研究概览
简要总结
This phase Ib trial studies the best dose of gemtuzumab ozogamicin when given together with CPX-351 in treating patients with acute myeloid leukemia that has come back after it was previously in remission. CPX-351 is a chemotherapy, which works in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Gemtuzumab ozogamicin is a monoclonal antibody, called gemtuzumab, linked to chemotherapy called calicheamicin. Gemtuzumab attaches to CD33 (transmembrane receptor) positive cancer cells in a targeted way and delivers ozogamicin to kill them. Giving CPX-351 and gemtuzumab ozogamicin may work better in treating patients with acute myeloid leukemia, compared to giving only one of these therapies alone.
详细描述
PRIMARY OBJECTIVES:
I. To determine the phase II dose of the combination liposome-encapsulated daunorubicin-cytarabine (CPX-351) plus gemtuzumab ozogamicin (GO) by means of estimating maximum tolerated dose (MTD) in participants with relapsed acute myeloid leukemia (AML).
SECONDARY OBJECTIVES:
I. To estimate the remission rate (complete remission plus complete remission with incomplete hematologic recovery) of participants in the MTD cohort who receive CPX-351 plus GO.
II. To evaluate CPX-351 plus GO as a bridge to allogeneic hematopoietic stem cell transplantation (HSCT) in participants with relapsed AML.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Bone marrow blasts >= 5% that develops after remission, no restriction on prior number of relapses or regimens
- •Eastern Cooperative Oncology Group (ECOG) 0-2
- •At least a 3-month duration of remission prior to relapse
- •Participants with relapse after allogeneic transplantation are included
- •Up to 1 cycle of hypomethylating agent monotherapy at time of relapse is allowed, must be discontinued at least 14 days prior to start of salvage induction
- •Serum total bilirubin =< 2.0 mg/dL, unless considered due to Gilbert?s disease or leukemia involvement
- •Aspartate aminotransferase (AST), alanine aminotransferase (ALT) =< 3 times the upper limit of normal, unless considered due to leukemia involvement
- •Alkaline phosphatase =< 3 times the upper limit of normal, unless considered due to leukemia involvement
- •Serum creatinine =< 2.0 mg/dL, or creatinine clearance > 40 mL/min based on Cockcroft-Gault glomerular filtration rate (GFR)
- •Ability to give full informed consent on their own
- •Females of reproductive potential (postmenopausal for less than 24 consecutive months) must have a negative pregnancy
排除标准
- •Currently receiving targeted therapy for FLT3 (cytokine receptor tyrosine kinase class III), IDH1, or IDH2 (isocitrate dehydrogenase, 1, 2) mutations and intent to continue use; prior use of targeted therapy for such mutations is allowed, but agents should be discontinued 1 week prior to enrollment
- •Acute promyelocytic leukemia
- •Second malignancy that would limit survival by less than 2 years
- •New York Heart Association class III or VI
- •Left ventricular ejection fraction < 50%
- •History of coronary stent placement that requires mandatory continuation of dual-antiplatelet therapy
- •History of Wilson?s disease or other copper handling disorders
- •Hypersensitivity to cytarabine, daunorubicin, or liposomal products
- •Active invasive fungal infection
- •Active bacterial or viral infection manifesting as fevers or hemodynamic instability within the past 72 hours
- •Lifetime cumulative daunorubicin-equivalent anthracycline dose > 368 mg/m^2
研究组 & 干预措施
Treatment (CPX-351, gemtuzumab ozogamicin)
INDUCTION: Patients receive liposome-encapsulated daunorubicin 44mg/m2 - cytarabine 100mg/m2 IV over 90 minutes on days 1, 3, and 5, and gemtuzumab ozogamicin 3 mg/m2 (max 4.5 mg) IV over 120 minutes on day 7, or days 4 and 7, or days 1, 4, and 7 in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION: Patients who achieve CR/CRi receive consolidation therapy at the discretion of the treating physician and/or proceed to allogeneic HSCT.
干预措施: Gemtuzumab Ozogamicin (Drug)
Treatment (CPX-351, gemtuzumab ozogamicin)
INDUCTION: Patients receive liposome-encapsulated daunorubicin 44mg/m2 - cytarabine 100mg/m2 IV over 90 minutes on days 1, 3, and 5, and gemtuzumab ozogamicin 3 mg/m2 (max 4.5 mg) IV over 120 minutes on day 7, or days 4 and 7, or days 1, 4, and 7 in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION: Patients who achieve CR/CRi receive consolidation therapy at the discretion of the treating physician and/or proceed to allogeneic HSCT.
干预措施: Liposome-encapsulated Daunorubicin-Cytarabine (Drug)
结局指标
主要结局
Maximum tolerated dose (MTD)
时间窗: Up to day 42
MTD is defined as the cohort of participants one cohort below the cohort that develop dose-limiting toxicity (DLT) in at least 2 participants.
次要结局
- Proportion of participants who go on to receive allogeneic hematopoietic cell transplantation (HSCT) after achieving CR/CRi(Up to 18 months)
- Duration of remission(Up to 18 months)
- Incidence of toxicities(Up to day 42)
- Objective response rate (ORR)(Up to day 42)
- Diagnosis of veno-occlusive disease (VOD)(Up to 18 months)
- Time to return of normal hematopoiesis(From day 1 of induction, assessed up to 18 months)
- Number of participants deceased at day 30 and day 60(At 30 and 60 days following the start of induction)