A Study of Hematopoietic Stem Cell Transplantation (HSCT) in Non-Malignant Disease Using a Reduced-Intensity Preparatory Regime
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 220
- 试验地点
- 42
- 主要终点
- Major toxicities as graded by the CTC v4
研究概览
简要总结
The hypothesis for this study is that a preparative regimen that maximizes host immunosuppression without myeloablation will be well tolerated and sufficient for engraftment of donor hematopoietic cells. It is also to determine major toxicities from these conditioning regimens, within the first 100 days after transplantation.
详细描述
The study uses reduced intensity conditioning that is immune suppressive to achieve donor cell engraftment without exposure to radiation or high dose chemotherapy in children with non-malignant disorders. The intent is to minimize early and late regimen related toxicities in the context of a reduced intensity regimen.
In addition to maximizing opportunity for donor cell engraftment, the trial seeks to minimize toxicities associated with transplant such as graft versus host disease and employs GVHD prophylaxis that seeks to decrease rates of acute and chronic GVHD in the setting of matched and mismatched donor stem cell transplants from marrow and cord blood sources.
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
- — 至 20 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Stratum 1: Patient must have non-malignant disorder, excluding thalassemia. Must be receiving a 8/8 HLA-matched bone marrow, related or unrelated Stratum 2: Patient must have thalassemia receiving 8/8 HLA-matched bone marrow or 5-8/8 HLA-matched UCB. Related or unrelated.
- •Stratum 3: Patient must have a hemoglobinopathy receiving 7/8 HLA-matched bone marrow or 5-8/8 HLA-matched UCB. Related or unrelated.
- •Stratum 4: Patient must have a non-malignant disorder (excluding hemoglobinopathy) receiving 7/8 HLA-matched bone marrow or 5-8/8 HLA-matched UCB. Related or unrelated.
- •All strata:
- •Recipient age < 21 years
- •Lansky/Karnofsky >/= 40
- •Adequate pulmonary, renal, liver, and other organ function as defined in protocol
- •Negative pregnancy test
- •Adequate total nucleated cell or CD34+ dose of product as defined in protocol
- •If sickle cell, Hemoglobin S <30%
排除标准
- •HIV positive
- •Invasive infection
- •Pregnancy/lactating
研究组 & 干预措施
Stratum 1
Recipients with non-malignant disorders, excluding thalassemia. Related or unrelated 8/8 HLA-matched bone marrow
干预措施: Treatment Plan 1: Stratum 1 (Drug)
Stratum 1
Recipients with non-malignant disorders, excluding thalassemia. Related or unrelated 8/8 HLA-matched bone marrow
干预措施: GVHD Regimen B: BM Recipients (Drug)
Stratum 2
Recipient with transfusion dependent thalassemia. Related or unrelated. 8/8 HLA-matched bone marrow or 5-8/8 HLA-matched UCB
干预措施: Treatment Plan 2: Strata 2, 3, or 4 (Drug)
Stratum 2
Recipient with transfusion dependent thalassemia. Related or unrelated. 8/8 HLA-matched bone marrow or 5-8/8 HLA-matched UCB
干预措施: GVHD Regimen A: UCB Recipients (Drug)
Stratum 2
Recipient with transfusion dependent thalassemia. Related or unrelated. 8/8 HLA-matched bone marrow or 5-8/8 HLA-matched UCB
干预措施: GVHD Regimen B: BM Recipients (Drug)
Stratum 3
Recipient with hemoglobinopathy Related or unrelated. 7/8 HLA-matched bone marrow or 5-8/8 HLA-matched UCB
干预措施: Treatment Plan 2: Strata 2, 3, or 4 (Drug)
Stratum 3
Recipient with hemoglobinopathy Related or unrelated. 7/8 HLA-matched bone marrow or 5-8/8 HLA-matched UCB
干预措施: GVHD Regimen A: UCB Recipients (Drug)
Stratum 3
Recipient with hemoglobinopathy Related or unrelated. 7/8 HLA-matched bone marrow or 5-8/8 HLA-matched UCB
干预措施: GVHD Regimen B: BM Recipients (Drug)
Stratum 4
Recipient with non-malignant disorder, excluding hemoglobinopathy Related or unrelated. 7/8 HLA-matched bone marrow or 5-8/8 HLA-matched UCB
干预措施: Treatment Plan 2: Strata 2, 3, or 4 (Drug)
Stratum 4
Recipient with non-malignant disorder, excluding hemoglobinopathy Related or unrelated. 7/8 HLA-matched bone marrow or 5-8/8 HLA-matched UCB
干预措施: GVHD Regimen A: UCB Recipients (Drug)
Stratum 4
Recipient with non-malignant disorder, excluding hemoglobinopathy Related or unrelated. 7/8 HLA-matched bone marrow or 5-8/8 HLA-matched UCB
干预措施: GVHD Regimen B: BM Recipients (Drug)
结局指标
主要结局
Major toxicities as graded by the CTC v4
时间窗: 100 days post-transplant
Toxicity monitoring includes unanticipated side effects (new) and all severe irreversible toxicities Grade 3 and above unexpected Grade 4 and above - all toxicities that are possibly, probably or definitely related to protocol therapy All deaths irrespective of attribution
Donor engraftment as measured by chimerism
时间窗: 100 days post-transplant
Engraftment is measured in myeloid and lymphoid lineage cells
次要结局
- Long-term donor engraftment by donor chimerism(2 years post-transplant)
- Incidence of chronic graft-versus-host disease as measured by protocol grading scale(2 years post-transplant)
- Immune reconstitution by laboratory evaluations(1 year post-transplant)
- Overall and disease free survival(2 years post-transplant)
- Time to neutrophil and platelet engraftment as measured by complete blood counts(Post transplant)
- Incidence of acute graft-versus-host disease as measured by protocol grading scale(100 days post-transplant)