Phase I/II Study De-intensifying Exposure of Post-transplantation Cyclophosphamide as GVHD Prophylaxis After HLA-haploidentical Hematopoietic Cell Transplantation for Hematologic Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 105
- 试验地点
- 1
- 主要终点
- aGVHD protection from a reduced duration of MMF, in combination with PTCy 25 mg/kg/day
研究概览
简要总结
Background:
Stem cell or bone marrow transplants can cure or control blood cancers. Sometimes the donor cells see the recipient's body as foreign. This can cause complications. A high dose of the drug cyclophosphamide (PTCy) can help reduce these risks. Researchers want to see if a lower dose of PTCy can have the same benefits. Based on encouraging results from the first part of the study, researchers now are investigating whether a lower dose of PTCy can allow other immunosuppression to be decreased.
Objective:
To see if a lower dose of PTCy and now also shorter duration of another immunosuppressant called mycophenolate mofetil will help people with blood cancers have a more successful transplant and fewer side effects.
Eligibility:
People ages 15-65 with leukemia, lymphoma, or multiple myeloma that is not curable with standard therapy and is at high risk of returning without transplant, and their healthy adult relatives
Design:
Transplant participants will be screened with:
Blood, urine, breathing, and heart tests
Scans
Chest x-ray
Bone marrow samples: A needle inserted into the participant s pelvis will remove marrow and a bone fragment.
Transplant recipients will stay at the hospital and be prepped with chemotherapy over 6 days for the transplant. They will get stem cells through a catheter in the chest or neck. They will get the cyclophosphamide chemotherapy. They will stay in the hospital about 4 more weeks. They will have blood transfusions. They will have frequent blood tests and 2 bone marrow samples within 1 year after the transplant.
Donor participants will be screened with:
Blood, urine, and heart tests
Chest x-ray
Scans
Donor participants will have bone marrow taken from their pelvis or stem cells taken from their blood. For the blood donation, blood will be taken from a vein in one arm, move through a machine to remove white blood cells, and be returned through a vein in the other arm.
Participation will last up to 5 years....
详细描述
Background:
Post-transplantation cyclophosphamide (PTCy) reduces rates of severe acute and chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT) and safely facilitates human leukocyte antigen (HLA)-haploidentical HCT
When clinically translated, the dose (50 mg/kg) and timing (days +3 and +4) of PTCy used were partly extrapolated from murine major histocompatibility complex (MHC)-matched skin allografting models and were partly empirical
In both MHC-haploidentical and MHC-disparate murine HCT models, a dose of 25 mg/kg/day was superior to 50 mg/kg/day on days +3 and +4 in terms of GVHD severity and mortality
In the MHC-haploidentical HCT model, a dose of 25 mg/kg on day +4 was equivalent to 25 mg/kg/day on days +3 and +4
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 120 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Phase I Pilot for Comparative Data
Standard PTCy 50 mg/kg/day on days +3 and +4, in a small pilot (up to 5 evaluable patients) for comparative data
干预措施: Fludarabine (Drug)
Phase I Dose De-escalation
PTCy at de-escalating doses (25 mg/kg/day on days +3 and +4, and PTCy 25 mg/kg on day +4) to assess for safety and determine Phase II dose (up to 12 evaluable patients)
干预措施: Busulfan (Drug)
Phase I Dose De-escalation
PTCy at de-escalating doses (25 mg/kg/day on days +3 and +4, and PTCy 25 mg/kg on day +4) to assess for safety and determine Phase II dose (up to 12 evaluable patients)
干预措施: Fludarabine (Drug)
Phase I Dose De-escalation
PTCy at de-escalating doses (25 mg/kg/day on days +3 and +4, and PTCy 25 mg/kg on day +4) to assess for safety and determine Phase II dose (up to 12 evaluable patients)
干预措施: Cyclophosphamide (Drug)
Phase I Dose De-escalation
PTCy at de-escalating doses (25 mg/kg/day on days +3 and +4, and PTCy 25 mg/kg on day +4) to assess for safety and determine Phase II dose (up to 12 evaluable patients)
干预措施: Mycophenolate Mofetil (Drug)
Phase I Dose De-escalation
PTCy at de-escalating doses (25 mg/kg/day on days +3 and +4, and PTCy 25 mg/kg on day +4) to assess for safety and determine Phase II dose (up to 12 evaluable patients)
干预措施: Sirolimus (Drug)
Phase I duration de-escalation of MMF
MMF at de-escalating duration (days +5 to +18 only, no MMF))
干预措施: Busulfan (Drug)
Phase I duration de-escalation of MMF
MMF at de-escalating duration (days +5 to +18 only, no MMF))
干预措施: Fludarabine (Drug)
Phase I duration de-escalation of MMF
MMF at de-escalating duration (days +5 to +18 only, no MMF))
干预措施: Cyclophosphamide (Drug)
Phase I duration de-escalation of MMF
MMF at de-escalating duration (days +5 to +18 only, no MMF))
干预措施: Mycophenolate Mofetil (Drug)
Phase I duration de-escalation of MMF
MMF at de-escalating duration (days +5 to +18 only, no MMF))
干预措施: Sirolimus (Drug)
Phase I Pilot for Comparative Data
Standard PTCy 50 mg/kg/day on days +3 and +4, in a small pilot (up to 5 evaluable patients) for comparative data
干预措施: Busulfan (Drug)
Phase I Pilot for Comparative Data
Standard PTCy 50 mg/kg/day on days +3 and +4, in a small pilot (up to 5 evaluable patients) for comparative data
干预措施: Cyclophosphamide (Drug)
Phase I Pilot for Comparative Data
Standard PTCy 50 mg/kg/day on days +3 and +4, in a small pilot (up to 5 evaluable patients) for comparative data
干预措施: Mycophenolate Mofetil (Drug)
Phase I Pilot for Comparative Data
Standard PTCy 50 mg/kg/day on days +3 and +4, in a small pilot (up to 5 evaluable patients) for comparative data
干预措施: Sirolimus (Drug)
Phase II Efficacy
PTCy at shortest duration, safe dose (from Phase I) to assess efficacy at providing adequate protection from grade 3-4 acute GVHD (up to 14 additional patients)
干预措施: Busulfan (Drug)
Phase II Efficacy
PTCy at shortest duration, safe dose (from Phase I) to assess efficacy at providing adequate protection from grade 3-4 acute GVHD (up to 14 additional patients)
干预措施: Fludarabine (Drug)
Phase II Efficacy
PTCy at shortest duration, safe dose (from Phase I) to assess efficacy at providing adequate protection from grade 3-4 acute GVHD (up to 14 additional patients)
干预措施: Cyclophosphamide (Drug)
Phase II Efficacy
PTCy at shortest duration, safe dose (from Phase I) to assess efficacy at providing adequate protection from grade 3-4 acute GVHD (up to 14 additional patients)
干预措施: Mycophenolate Mofetil (Drug)
Phase II Efficacy
PTCy at shortest duration, safe dose (from Phase I) to assess efficacy at providing adequate protection from grade 3-4 acute GVHD (up to 14 additional patients)
干预措施: Sirolimus (Drug)
Phase II efficacy of reduced duration MMF
MMF at duration identified from de-escalation evaluation.
干预措施: Busulfan (Drug)
Phase II efficacy of reduced duration MMF
MMF at duration identified from de-escalation evaluation.
干预措施: Fludarabine (Drug)
Phase II efficacy of reduced duration MMF
MMF at duration identified from de-escalation evaluation.
干预措施: Cyclophosphamide (Drug)
Phase II efficacy of reduced duration MMF
MMF at duration identified from de-escalation evaluation.
干预措施: Mycophenolate Mofetil (Drug)
Phase II efficacy of reduced duration MMF
MMF at duration identified from de-escalation evaluation.
干预措施: Sirolimus (Drug)
结局指标
主要结局
aGVHD protection from a reduced duration of MMF, in combination with PTCy 25 mg/kg/day
时间窗: 60 days
The fraction of evaluable patients who experience grade III-IV aGVHD at day +60 will be determined and reported along with 80% and 95% two-sided confidence intervals. The MMF duration level patients may be compared with the PTCy dose level patients which serves as a baseline for standard duration MMF.
aGVHD protection from PTCy 25 mg/kg
时间窗: 60 days
The fraction of evaluable patients who experience grade III-IV aGVHD at day +60 will be determined and reported along with 80% and 95% two-sided confidence intervals.
次要结局
- Determine, at the PTCy dose or MMF duration used in phase II cohorts, the cumulative incidences(100 days)
- determine the shortest MMF duration without unacceptable acute GVHD to be used during phase II(60 days)