Phase I/II Clinical Trial of Daratumumab and Donor Lymphocyte Infusion in Patients With Relapsed Acute Myeloid Leukemia Post-Allogeneic Hematopoietic Stem Cell Transplant
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 4
- 试验地点
- 1
- 主要终点
- Safety and Feasibility Defined as the Establishment of the Appropriate Dose Level of Donor Lymphocyte Infusion When Given With a Fixed Dose of Daratumumab
研究概览
简要总结
This phase I/II trial studies the side effects and best dose of donor lymphocyte infusions when given together with daratumumab and to see how well they work in treating participants with acute myeloid leukemia that has come back after a stem cell transplant. A donor lymphocyte infusion is a type of therapy in which lymphocytes (white blood cells) from the blood of a donor are given to a participant who has already received a stem cell transplant from the same donor. The donor lymphocytes may kill remaining cancer cells. Monoclonal antibodies, such as daratumumab, may interfere with the ability of cancer cells to grow and spread. Giving daratumumab and donor white blood cells may work better in treating participants with acute myeloid leukemia.
详细描述
PRIMARY OBJECTIVES:
I. To evaluate safety and tolerability of daratumumab and escalating doses of donor lymphocyte infusions (DLI) in post-hematopoietic cell transplantation (HCT) patients with relapsed acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) transformed to AML (phase I).
II. To evaluate overall response rate to daratumumab and DLI in patients with post-HCT relapsed AML and MDS (phase II).
SECONDARY OBJECTIVES:
I. To assess overall response rates in minimal residual disease (MRD) positive patients and in patients with overt morphological relapse.
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
- •AML relapse following Allo-HSCT (Morphological relapse, or MRD positive verified by flow cytometry, cytogenetics, and molecular mutations)
- •Relapsed/Refractory AML must not be candidates for available therapies known to be effective for treatment of their AML.
- •MDS transformed to AML following Allo-HCT
- •Patients who received a 10/10 HLA-matched allogeneic HCT either from sibling donors or unrelated donors or atleast a 5/10 haploidentical transplant.
- •Engraftment must have occurred as defined by platelet (PLT) count > 20,000/µL and ANC
- •Eastern Cooperative Oncology Group (ECOG) performance status < 3
- •Creatinine clearance > 40 ml/min (calculated or measured)
- •Aspartate aminotransferase (AST) < 3 x upper limit of normal (ULN), alanine aminotransferase (ALT) < 3 x ULN
- •Total bilirubin < 1.5 x ULN
- •Off calcineurin inhibitors for at least 2 weeks
- •Prednisone dose ≤ 20 mg/day
- •Patients with proliferative disease can be cytoreduced with cytotoxic chemotherapy at Investigator discretion, but there should be at least a 14 day window between start of cytoreductive therapy and start of daratumumab
- •Blast count ˂20K/day (hydrea use is allowed)
排除标准
- •No demonstrable evidence of donor chimerism (˂ 55% donor CD3 or CD33 chimerism)
- •Patients with a molecular mutation without chromosomal abnormalities or declining chimerisms (MRD status must be verified by surface marker and mutational analyses)
- •Active graft-versus-host disease (GvHD) grades II-IV; prior acute GVHD could have occurred but resolved at time of initiation of daratumumab
- •Extensive chronic GvHD requiring ongoing immunosuppression with calcineurin inhibitors
- •Patients with FLT3+ AML or blast crisis CML who have not yet received post-transplant TKI therapy
- •Active central nervous system (CNS) disease testicular disease
- •EXCEPTION: Subjects with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR.; seropositive for hepatitis C (except in the setting of a sustained virologic response [SVR], defined as aviremia at least 12 weeks after completion of antiviral therapy).
- •Patients must not have moderate or severe persistent asthma within the past 2 years and must not have currently uncontrolled asthma of any classification.
- •History of grade IV anaphylactic reaction to monoclonal antibody therapy
- •Active autoimmune disease prior to transplant
- •Concurrent use of any other investigational drugs
研究组 & 干预措施
Treatment (DLI, daratumumab)
Participants receive daratumumab intravenously once a week for 8 weeks and donor lymphocyte infusion in weeks 3 or 4 in the absence of disease progression or unacceptable toxicity.
干预措施: Daratumumab (Biological)
Treatment (DLI, daratumumab)
Participants receive daratumumab intravenously once a week for 8 weeks and donor lymphocyte infusion in weeks 3 or 4 in the absence of disease progression or unacceptable toxicity.
干预措施: Donor Lymphocyte Infusion (Procedure)
Treatment (DLI, daratumumab)
Participants receive daratumumab intravenously once a week for 8 weeks and donor lymphocyte infusion in weeks 3 or 4 in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
结局指标
主要结局
Safety and Feasibility Defined as the Establishment of the Appropriate Dose Level of Donor Lymphocyte Infusion When Given With a Fixed Dose of Daratumumab
时间窗: Up to 6 months
次要结局
- Minimal Residual Disease (MRD) Conversion Rates(Up to 6 months)
- Rates of Complete Remission(Up to 6 months)
- Post-relapse Progression-free Survival(At 6 months)
- Post-relapse Overall Survival(Up to 6 months)
研究者
Sumithira Vasu
Principal Investigator
Ohio State University Comprehensive Cancer Center