CD3/CD19 Depleted or CD3 Depleted/CD56 Selected Haploidentical Donor Natural Killer (NK) Cell Based Therapy for AML Patients Not in CR
A Randomized Trial Comparing CD3/CD19 Depleted or CD3 Depleted/CD56 Selected Haploidentical Donor Natural Killer (NK) Cell Based Therapy for Adults With Acute Myelogenous Leukemia Who Have Failed 1 or 2 Induction Attempts
This is a phase II trial designed to test the safety and efficacy (complete response [CR]) of related donor HLA-haploidentical NK-cell based therapy for the treatment of acute myelogenous leukemia (AML).
Patients with newly diagnosed AML who failed to achieve a complete remission (CR) after one or two standard induction attempts receive after a preparative regimen of cyclophosphamide and fludarabine a single infusion of CD3-/CD19- NK cells or CD3-/CD56+ NK cells followed by a short course of Interleukin-2 (IL-2) to facilitate NK cell survival and expansion.
研究概览
详细说明
This trial uses a Simon's two-stage design to estimate the complete remission rate at day +42 post NK cell infusion. The trial includes an initial randomized sub- study of 24 patients during stage 1 to choose which of the enriched NK cell products (CD3-/CD19- versus CD3-/CD56+) should be used to complete the trial based on successful in vivo NK cell expansion. This parameter is defined as 40% donor DNA and 40% of lymphocytes are NK cells at day 7 post infusion OR 20% donor DNA and 20% of lymphocytes are NK cells at day 14 post infusion. Twelve patients will be randomized to each product.
Enrollment Plan:
Stage 1: Enroll 24 patients with 1:1 randomization for NK cell processing (CD3-/CD19- versus CD3-/CD56+) Stage 2: Enroll an additional 17 patients using the optimal NK cell product identified during stage 1.
If neither product achieves success at the end of stage 1, the study will stop and the platform redesigned
研究类型
注册 (实际的)
阶段
- 不适用
联系人和位置
学习地点
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Illinois
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Chicago、Illinois、美国、60637
- Universtiy of Chicago
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Minnesota
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Minneapolis、Minnesota、美国、55455
- University of Minnesota
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Ohio
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Columbus、Ohio、美国、43210
- Ohio State University
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- Newly diagnosed with acute myelogenous leukemia (except acute promyelocytic leukemia) and has failed one or two prior standard induction attempts. Failure is defined as:
- ≥ 30% bone marrow blasts with at least 20% cellularity at mid-cycle bone marrow biopsy or residual AML on subsequent~ day 28 bone marrow biopsy by morphology, flow, PCR or FISH
- Patients enrolling after only 1 failed induction attempt must meet at least one of the following additional eligibility criteria of high risk: ≥ 60 years of age adverse cytogenetics or molecular characteristics
- AML that progressed out of myelodysplastic syndrome (MDS) is eligible if the patient did not receive treatment directed at the MDS
- HLA-haploidentical related donor (aged 12 to 70 years)
- ≥ 18, but < 75 years of age
- Karnofsky performance status ≥ 60%
- Adequate organ function within 14 days of study registration (30 days for pulmonary and cardiac) as defined in section 4.5
- Ability to be off prednisone and other immunosuppressive drugs for at least 3 days prior to the NK cell infusion (excluding preparative regimen pre-meds)
- No prior hematopoietic transplant
- Not pregnant or lactating
- Sexually active females of childbearing potential and males with partners of child bearing potential must agree to use birth control
Exclusion Criteria:
- Pregnant or lactating as the treatments used in this study includes drugs that are FDA Pregnancy Category D.
- Acute leukemias of ambiguous lineage
- AML that transformed from previously treated myelodysplastic syndromes
- Prior hematopoietic transplant
- New or progressive pulmonary infiltrates on screening chest x-ray or chest CT scan that has not been cleared by Pulmonary. Infiltrates attributed to infection must be stable/improving (with associated clinical improvement) after 1 week of appropriate therapy (4 weeks for presumed or documented fungal infections)
- Uncontrolled bacterial, fungal, or viral infections including HIV - chronic asymptomatic viral hepatitis is allowed
- Known hypersensitivity to one or more of the study agents used
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:不适用
- 介入模型:单组作业
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
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其他:Single-arm trial
Multi-center, open-label, single-arm, phase I/II clinical trial
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CliniMACS® CD3 and CD19 Reagent System
其他名称:
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研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
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The Primary Endpoint of the Study is Complete Remission (±3 Days)
大体时间:On Day+42 (+/- 3 days) after NK cell infusion
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Both the number of patients with leukemia in complete remission and the number of patients with leukemia not in complete remission will be reported.
Leukemia remission status will be assessed according to the Revised Recommendations of The International Working Group (J Clin Oncol 21:4642-4649, 2003).
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On Day+42 (+/- 3 days) after NK cell infusion
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
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The Secondary Endpoint is the Expansion and Persistence of NK Cells to be Used for the Remainder of the Study.
大体时间:Day+7 to Day+42 after NK cell infusion
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Successful expansion and persistence of NK cells is defined as ≥ 100 donor derived NK cells per µl blood.
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Day+7 to Day+42 after NK cell infusion
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合作者和调查者
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.
急性髓性白血病的临床试验
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Shenzhen Second People's Hospital招聘中白血病 | 骨髓的 | 慢性的 | BCR-ABL (Breakpoint Cluster Region-abelson Murine Leukemia) | 积极的中国