Conditioning for Graft Failure After Hematopoietic Stem Cell Transplantation
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Survival at 100 Days Post Transplant
研究概览
简要总结
RATIONALE: Antithymocyte globulin, clofarabine, and rituximab may stop the patient's immune system from rejecting the donor's stem cells when they do not exactly match the patient's blood. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving antithymocyte globulin before transplant and cyclosporine and mycophenolate mofetil before and after transplant may stop this from happening.
PURPOSE: This phase II trial is studying how well giving antithymocyte globulin together with clofarabine and rituximab works in treating patients after an unsuccessful stem cell transplant.
详细描述
OBJECTIVES:
Primary
- To determine the rate of sustained donor engraftment at 42 days and survival at 100 days post transplantation in patients treated with anti-thymocyte globulin, clofarabine, and rituximab.
Secondary
- To determine incidence of treatment-related mortality at day 100 post transplantation.
- To determine incidence of neutrophil recovery by day 42 post transplantation.
- To determine survival at day 100 and 1 year post transplantation.
- To determine the proportion of patients with chimerism at day 28 post transplantation.
- To determine incidence and severity of grades II-IV acute graft-vs-host disease by day 100 post transplantation.
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
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Timing of relevant evaluations: Taking in account the need for rapid intervention, if white blood count is less than 200 on day +20, bone marrow aspirate should be performed on day +
- •Unless there is an increase in absolute neutrophil count (ANC) to > 500 in the following 7 days, bone marrow aspirate should be repeated on day +
- •If the white blood count is still less than 200 and bone marrow is acellular, bone marrow (BM) or peripheral blood stem cell (PBSC) donor should be reactivated and availability of cord blood (CB) units assessed. If the BM or PBSC donor is not confirmed within 14 days of the request for the donation (typically second donation from the same donor), CB unit should be used instead.
- •Primary or secondary graft failure after hematopoietic stem cell transplantation defined as a > 50% loss of donor chimerism from previous maximum or less than 25% donor beyond day +42 with pancytopenia and no evidence of relapse. Patients with any diagnosis, type of donor, hematopoietic cell graft or conditioning regimen should be considered for this study.
- •primary graft failure is defined as:
- •ANC < 500
- •BM < 10% on two occasions (Day +21 and Day +28)
- •Donor chimerism need not to be considered, provided there is no evidence of malignancy
- •secondary graft failure is defined as < 5% cellularity and ANC < 500 for more than 7 days any time after primary engraftment).
- •Women of childbearing potential must agree to use adequate contraception (diaphragm, birth control pills, injections, intrauterine device [IUD], surgical sterilization, subcutaneous implants, or abstinence, etc.) for the duration of treatment.
- •Patients or their guardian are able and willing to provide written informed consent.
排除标准
- •The presence of any of the following excludes a patient from study enrollment:
- •Uncontrolled active infection defined as more than one week with no response to appropriately chosen antibiotics
- •Evidence of recurrence of primary malignancy.
- •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 age must use appropriate methods as described.
- •Allergy to rituximab.
- •Evidence of HIV infection or positive HIV serology.
- •Autologous recovery defined as defined as greater than 90% recipient PCR product in the competitive VNTR PCR performed on gradually increasing white blood cell count.
- •Donor Inclusion Criteria:
- •Related donors must be 2-75 years of age and in good health.
- •Meets match criteria
- •Able and willing to undergo cell collection procedures (bone marrow cell collection or leukapheresis)
- •Not pregnant or lactating.
- •HIV-1, HIV-2 negative; HTLV-1, HTLV-2 negative, Hepatitis B and C negative.
- •Patients or their guardian are able and willing to provide informed consent
研究组 & 干预措施
Conditioning for Graft Failure
Primary or secondary graft failure after hematopoietic stem cell transplantation defined as a > 50% loss of previously best donor chimerism or less than 25% donor chimerism beyond day +42 with pancytopenia and no evidence of relapse. Patients with any diagnosis, type of donor, hematopoietic cell graft or conditioning regimen should be considered for this study. Patients receive anti-thymocyte globulin, rituximab, and clofarabine.
干预措施: anti-thymocyte globulin (Biological)
Conditioning for Graft Failure
Primary or secondary graft failure after hematopoietic stem cell transplantation defined as a > 50% loss of previously best donor chimerism or less than 25% donor chimerism beyond day +42 with pancytopenia and no evidence of relapse. Patients with any diagnosis, type of donor, hematopoietic cell graft or conditioning regimen should be considered for this study. Patients receive anti-thymocyte globulin, rituximab, and clofarabine.
干预措施: rituximab (Biological)
Conditioning for Graft Failure
Primary or secondary graft failure after hematopoietic stem cell transplantation defined as a > 50% loss of previously best donor chimerism or less than 25% donor chimerism beyond day +42 with pancytopenia and no evidence of relapse. Patients with any diagnosis, type of donor, hematopoietic cell graft or conditioning regimen should be considered for this study. Patients receive anti-thymocyte globulin, rituximab, and clofarabine.
干预措施: clofarabine (Drug)
Conditioning for Graft Failure
Primary or secondary graft failure after hematopoietic stem cell transplantation defined as a > 50% loss of previously best donor chimerism or less than 25% donor chimerism beyond day +42 with pancytopenia and no evidence of relapse. Patients with any diagnosis, type of donor, hematopoietic cell graft or conditioning regimen should be considered for this study. Patients receive anti-thymocyte globulin, rituximab, and clofarabine.
干预措施: stem cell transplantation (Procedure)
结局指标
主要结局
Survival at 100 Days Post Transplant
时间窗: Day 100 post transplantation
Percent of patients alive from beginning of study to Day 100 post transplantation
Rate of Sustained Donor Engraftment
时间窗: Day 42 post transplantation
Rate of Sustained Donor Engraftment is defined as the percent of paticipants with an absolute neutrophile count (ANC) of 500 or more without a subsequent graft rejection.
次要结局
- Time to Primary Neutrophil Engraftment(Day 42 post transplantation)
- Survival(One year post transplantation)
- Acute Graft-vs-host Disease(Day 30-100)
- Treatment-related Death(Day 100 post transplantation)
- Chimerism(Day 28 post transplantation)