Use of Cyclophosphamide/Fludarabine to Promote in Vivo Expansion of Donor Lymphocyte Infusions (DLI) to Enhance Efficacy After Allogeneic Transplant
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 57
- 试验地点
- 1
- 主要终点
- Number of Patients Alive
研究概览
简要总结
The purpose of this study is to test the hypothesis that a pre-infusion preparative regimen of cyclophosphamide and fludarabine will improve the effectiveness of DLI in patients with blood cancers.
详细描述
When cancer relapses after donor bone marrow transplantation, regular dose chemotherapy offers little hope of prolonged survival. However, there is evidence that lymphocytes can attack cancer cells. There is considerable evidence that this immune attack on cancer cells is associated with graft-versus-host disease. Although graft-versus-host disease can cause problems, this immune reaction may, in part, be the way that bone marrow transplantation cures cancer. In this study we hope that infusion of immune cells from the subject's bone marrow donor plus a chemotherapy regimen of cyclophosphamide and fludarabine will activate the subject's immune system to attack their cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Year 至 70 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients (age > or = 1 years) with a diagnosis of relapse after related or unrelated allogeneic stem cell transplantation for a hematological malignancy.
- •For CML, relapse will be defined as any cytogenetic evidence of a Philadelphia chromosome or persistence of BCR/ABL rearrangements by molecular testing on at least two measurements over a 6 month interval. If cytogenetics are normal and there is PCR evidence of a BCR/ABL fusion, patients will be eligible if they have evidence of a quantitative increase in CML measured either by quantitative PCR or by fluorescent in situ hybridization (FISH).
- •For non-CML, relapse will be defined based on disease specific morphologic criteria from a bone marrow biopsy and aspirate or recurrence of disease specific cytogenetics. For disease specific definition of relapse, see appendix
- •Relapse can be determined morphologically with less than 5 percent blasts if definitive relapse can be determined. Equivocal results for relapse should result in a repeated test after an appropriate time interval (suggested 1 month) to determine eligibility.
- •Post-transplant lymphoproliferative diseases (often referred to as EBV-associated lymphomas) are NOT eligible for this protocol.
- •For Chronic Phase CML patients only
- •- must have failed (no response in 3 months or incomplete response at 6 months) or refused treatment with Gleevec
- •- if no prior DLI, CML patients will first have DLI- if relapse occurs after DLI, DLI with chemotherapy per this protocol will be offered
- •Patients must be within one year of identification of relapse or if beyond that time period, must have at least 10% donor DNA by RFLP or cytogenetics.
- •Same allogeneic donor (sibling or URD) used for transplantation is available for lymphocyte donation.
- •No severe organ damage (by laboratory or clinical assessment) as measured by:
- •- blood creatinine ≤ 2.0 mg/dL
- •- liver function tests < 5 x normal
- •- left ventricular ejection fraction > 40% (testing required only if symptomatic or prior known impairment).
- •- pulmonary functions > 50% (testing required only if symptomatic or prior known impairment). Oxygen saturation (>92%) can be used in child where PFT's cannot be obtained.
- •- chest x-ray without evidence of active infection
- •Off prednisone and other immunosuppressive agents (given for any reason) for at least 3 days prior to DLI infusions.
- •Performance status ≥ 60%
- •Women must not be pregnant or lactating. The agents used in this study may be teratogenic to a fetus and there is no information on the excretion of agents into breast milk All females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy
- •Women of childbearing potential and sexually active males are strongly advised to use an accepted and effective method of contraception
- •Patient must given written informed consent indicating understanding of the nature of the treatment and its potential risks
排除标准
- •Concurrent signs of acute or chronic graft-versus-host disease requiring ongoing treatment at the time of relapse will be ineligible.
- •Patients being treated for GVHD with prednisone, cyclosporine, Imuran or other immunosuppressive medications are not eligible until these medications are discontinued for at least 2 weeks without a flare of GVHD.
- •Active CNS leukemia
- •Active fungal infection or pulmonary infiltrates (stable prior treated disease is allowable)
- •HIV positive
研究组 & 干预措施
CML
Patients with Chronic Myelogenous Leukemia (CML) who have failed or refused Gleevec(TM) therapy and will receive Donor Lymphocyte Infusion.
干预措施: Donor Lymphocyte Infusion (Procedure)
Non-CML or CML that Relapsed after Donor Lymphocyte Infusion
Patients with non-CML or CML who have failed Donor Lymphocyte Infusion (DLI) and will receive induction chemotherapy plus DLI.
干预措施: Donor Lymphocyte Infusion (Procedure)
Non-CML or CML that Relapsed after Donor Lymphocyte Infusion
Patients with non-CML or CML who have failed Donor Lymphocyte Infusion (DLI) and will receive induction chemotherapy plus DLI.
干预措施: Induction Chemotherapy (Drug)
结局指标
主要结局
Number of Patients Alive
时间窗: 1 Year
The percentage of people in a study or treatment group who are alive for a certain period of time after they were diagnosed with or treated for a disease, such as cancer. Also called survival rate. Overall survival will be defined as time from date of enrollment to date of death or censored at the date of last documented contact for patients still alive.
次要结局
- Number of Patients Alive Without Disease(1 Year)
- Number of Participants With Complete Remission(one year)
- Number of Patients With Acute Graft-Versus-Host Disease(Day 100)
- Number of Patients With Bone Marrow Aplasia(Day 100)