A Phase II Trial of Myeloablative Conditioning and Transplantation of Partially HLA-mismatched Bone Marrow for Patients With Hematologic Malignancies
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 107
- 试验地点
- 2
- 主要终点
- Engraftment as Measured by Donor Chimerism
研究概览
简要总结
The purpose of this study is to see if giving high dose chemotherapy and total body irradiation before and repeating high dose chemotherapy after a bone marrow transplant could reduce the incidence of graft rejection and disease for patients with blood cancers
详细描述
Allogeneic blood or marrow transplantation (alloBMT), following either marrow-ablative or nonmyeloablative conditioning, is a potentially curative treatment for a variety of hematologic malignancies and non-malignant hematologic disorders. Of all the potential sources of allografts, transplantation of stem cells from a human leukocyte antigen (HLA)-matched sibling has generally produced the best overall outcomes, i.e. overall and progression-free survival. Unfortunately, only about a third of candidates for alloBMT have HLA-matched siblings.
For patients who lack HLA-matched siblings, there are three alternative sources of stem cells for alloBMT: 1) volunteer unrelated donors; 2) umbilical cord blood; and 3) partially HLA-mismatched, or haploidentical, related donors. Since any patient shares exactly one HLA haplotype with each biological parent or child and half of siblings, an eligible haploidentical donor can be identified rapidly in nearly all cases. However, haploidentical BMT has been associated with significant risks of graft rejection and severe GVHD, which are manifestations of excessive alloreactivity by host and donor T cells, respectively.
The risk of severe GVHD may be reduced in intensively conditioned recipients of grafts that have been rigorously depleted of mature T cells or selectively depleted of alloreactive T cells, but the risks of serious infection and death from prolonged immune compromise in these patients remains high. Cyclophosphamide(Cy) is a highly immunosuppressive antineoplastic agent that has an established role in conditioning for alloBMT.
Typically, the drug is administered prior to transplantation to prevent graft rejection by suppressing the host immune system. However, pre-transplantation conditioning with Cy increases the risk of GVHD following allogeneic T cell infusion in mouse models. In contrast, administration of a properly timed, high dose of Cy after BMT inhibits both graft rejection and GVHD.
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
- 年龄范围
- 6 Months 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Acute lymphocytic leukemia in high risk CR1
- •Acute myeloid leukemia in CR1
- •Therapy-related AML
- •RAEB with >5% and <20% bone marrow blasts
- •Chronic myelogenous leukemia beyond 1st chronic phase; Patients cannot be in blast crisis
- •Chemotherapy-resistant Hodgkins Lymphoma or intermediate or high grade Non-Hodgkins lymphoma (Less than a PR after standard or salvage chemotherapy)
- •Mantle cell lymphoma: chemotherapy refractory (Less than a PR after standard or salvage chemotherapy) or patients beyond CR1 with chemosensitive disease
- •Follicular Lymphoma, Grade 3
- •Transformed indolent lymphomas
排除标准
- •Poor cardiac function: left ventricular ejection fraction <45% as determined by MUGA or ECHO. For pediatric patients LVEF <45% or a shortening fraction below normal limits for age.
- •Poor pulmonary function: FEV1 and FVC <50% predicted for patients who have not received thoracic or mantle irradiation. For patients who have received thoracic or mantle irradiation, FEV1 and FVC <70% predicted or DLCO < 50 of predicted. For children unable to perform PFTs because of developmental stage pulse oximetry < 85% on RA
- •Poor liver function: bilirubin >2 mg/dl (not due to hemolysis, Gilbert's or primary malignancy)
- •Poor renal function: Creatinine >2.0mg/dl or creatinine clearance
- •HIV-positive
- •Positive leukocytotoxic crossmatch
- •Women of childbearing potential who currently are pregnant or who are not practicing adequate contraception
- •Uncontrolled viral, bacterial, or fungal infections Patients with symptoms consistent with RSV, influenza A, B, or parainfluenza at the time of enrollment will be assayed for the above viruses and if positive are not eligible for the trial until they are no longer symptomatic (patients may have continued assay positivity for a period of time post resolution of symptoms secondary to the nature of the assay.
- •Indolent lymphomas (Follicular Grade 1 and 2, marginal zone, chronic lymphocytic leukemia, small lymphocytic lymphoma, MALT)
研究组 & 干预措施
Myeloablative haploidentical BMT
- All participants except those with acute lymphoblastic leukemia and lymphoblastic lymphoma: Busulfan will be administered 1 mg/kg oral (or 0.8 mg/kg IV) four times per day for four days, followed by cyclophosphamide 50 mg/kg once per day for two days.
- Participants with acute lymphocytic leukemia or lymphoblastic lymphoma: Cyclophosphamide will be administered 50 mg/kg once per day for two days, followed by total body irradiation at 300 cGy per day for four days.
干预措施: Busulfan (Drug)
Myeloablative haploidentical BMT
- All participants except those with acute lymphoblastic leukemia and lymphoblastic lymphoma: Busulfan will be administered 1 mg/kg oral (or 0.8 mg/kg IV) four times per day for four days, followed by cyclophosphamide 50 mg/kg once per day for two days.
- Participants with acute lymphocytic leukemia or lymphoblastic lymphoma: Cyclophosphamide will be administered 50 mg/kg once per day for two days, followed by total body irradiation at 300 cGy per day for four days.
干预措施: Cyclophosphamide (Drug)
Myeloablative haploidentical BMT
- All participants except those with acute lymphoblastic leukemia and lymphoblastic lymphoma: Busulfan will be administered 1 mg/kg oral (or 0.8 mg/kg IV) four times per day for four days, followed by cyclophosphamide 50 mg/kg once per day for two days.
- Participants with acute lymphocytic leukemia or lymphoblastic lymphoma: Cyclophosphamide will be administered 50 mg/kg once per day for two days, followed by total body irradiation at 300 cGy per day for four days.
干预措施: Total body irradiation (Radiation)
结局指标
主要结局
Engraftment as Measured by Donor Chimerism
时间窗: Day 60
Percentage of participants who achieved donor chimerism \>=95%.
次要结局
- Acute GVHD(Day 100)
- Survival(1 year, 2 years, 3 years)
- Non-relapse Mortality(Day 100, 1 year)
- Chronic GVHD(6 months, 12 months)
- Relapse(1 year, 3 years)