Reduced Intensity (RIC) Conditioning And Transplantation of HLA-Haploidentical Related Hematopoietic Cells (Haplo-HCT) For Patients With Hematologic Malignancies
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 78
- 试验地点
- 1
- 主要终点
- Disease-free Survival (DFS)
研究概览
简要总结
This is a single institution phase II study of a reduced intensity conditioning (RIC) followed by a haploidentical hematopoietic cell transplant (haplo-HCT) in persons with diagnosis of hematologic malignancy. Conditioning will consists of fludarabine, cyclophosphamide, melphalan and total body irradiation (TBI) preparative regimen with a melphalan dose reduction for patients ≥55 years old and those with HCT Comorbidity Index (CI) >3. This study uses a two-stage phase II design with accrual goal of 84 patients, using 28 patients separately for arms A, C and D
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 75 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Karnofsky performance status of ≥70% or Lansky play score ≥ 70%
- •A related haploidentical bone marrow donor with up to 2 or 3 HLA locus-mismatches
- •The donor and recipient must be HLA identical for at least one haplotype (using high resolution DNA based typing) at the following genetic loci: HLA-A, HLA-B, HLA-C, and HLA-DRB
- •Adequate liver and renal function
- •Absence of decompensated congestive heart failure, or uncontrolled arrhythmia and left ventricular ejection fraction ≥ 40%
- •Diffusion capacity corrected (DLCOcorr) > 40% predicted, and absence of O2 requirements
- •> 6 months after prior autologous transplant (if applicable)
- •Agrees to use contraception during study treatment
- •Voluntary written consent (adult or parent/guardian with presentation of the minor information sheet, if appropriate)
- •Patients who are HIV+ must have undetectable viral load. All HIV+ patients must be evaluated by Infectious Disease (ID) and a HIV management plan establish prior to transplantation
排除标准
- •< 70 years with an available 5-6/6 HLA-A, B, DRB1 matched sibling donor
- •Pregnancy or breastfeeding
- •Current active and uncontrolled serious infection
- •Acute leukemia in morphologic relapse/persistent disease defined as > 5% blasts in normocellular bone marrow OR any % blasts if blasts have unique morphologic markers (e.g. Auer rods).
- •CML in blast crisis
- •Large cell lymphoma, mantle cell lymphoma and Hodgkin disease that is progressive on salvage therapy.
- •stable non-bulky disease is acceptable.
- •Active central nervous system malignancy
- •Criteria For Donor Selection:
- •Donors must be HLA-haploidentical relatives of the patient, defined as having a shared HLA haplotype between donor and patient at HLA-A, -B, -C, and -DRB
- •Eligible donors (14-70 years old) include biological children, siblings or half siblings, or parents, able and willing to undergo bone marrow harvesting.
- •For donors <18 years, the maximum recipient weight (actual body weight) should not exceed 1.25 times the donor weight (actual body weight)1 In addition, bone marrow product volume should be limited to 20 ml/kg donor weight for donors <18 years.
研究组 & 干预措施
Arm A: Haplo-HCT <55 years old
Reduced-intensity conditioning and transplantation of human leukocyte antigen (HLA) -haploidentical related donor stem cells for patients <55 years old with hematopoietic cell transplantation Comorbidity Index (HCT-CI) ≤2
干预措施: Haplo HCT <55 years old (Biological)
Arm A: Haplo-HCT <55 years old
Reduced-intensity conditioning and transplantation of human leukocyte antigen (HLA) -haploidentical related donor stem cells for patients <55 years old with hematopoietic cell transplantation Comorbidity Index (HCT-CI) ≤2
干预措施: GVHD Prophylaxis (Drug)
CLOSED Arm B: Haplo-HCT ≥55 years old
Reduced-intensity conditioning and transplantation of human leukocyte antigen (HLA) -haploidentical related donor stem cells for patients ≥55 years old or younger with hematopoietic cell transplantation Comorbidity Index (HCT-CI) ≥3.
干预措施: Haplo HCT ≥55 years old (Biological)
CLOSED Arm B: Haplo-HCT ≥55 years old
Reduced-intensity conditioning and transplantation of human leukocyte antigen (HLA) -haploidentical related donor stem cells for patients ≥55 years old or younger with hematopoietic cell transplantation Comorbidity Index (HCT-CI) ≥3.
干预措施: GVHD Prophylaxis (Drug)
Arm C: Haplo-HCT HCT-CI ≤2 aged ≥55 and < 65yo
Reduced-intensity conditioning and transplantation of human leukocyte antigen (HLA) -haploidentical related donor stem cells for patients with hematopoietic cell transplantation Comorbidity Index (HCT-CI) ≤2 aged ≥55 and < 65 years old.
干预措施: GVHD Prophylaxis (Drug)
Arm C: Haplo-HCT HCT-CI ≤2 aged ≥55 and < 65yo
Reduced-intensity conditioning and transplantation of human leukocyte antigen (HLA) -haploidentical related donor stem cells for patients with hematopoietic cell transplantation Comorbidity Index (HCT-CI) ≤2 aged ≥55 and < 65 years old.
干预措施: Haplo HCT ≥55 and < 65 years old (Biological)
Arm D: Haplo-HCT aged ≥65 and ≤75yo OR any age HCT-CI ≥3
Reduced-intensity conditioning and transplantation of human leukocyte antigen (HLA) -haploidentical related donor stem cells for patients patients ≥65 and ≤75 years old OR any age group with hematopoietic cell transplantation Comorbidity Index (HCT-CI) ≥3.
干预措施: GVHD Prophylaxis (Drug)
Arm D: Haplo-HCT aged ≥65 and ≤75yo OR any age HCT-CI ≥3
Reduced-intensity conditioning and transplantation of human leukocyte antigen (HLA) -haploidentical related donor stem cells for patients patients ≥65 and ≤75 years old OR any age group with hematopoietic cell transplantation Comorbidity Index (HCT-CI) ≥3.
干预措施: Haplo HCT ≥65 and ≤75 years old (Biological)
结局指标
主要结局
Disease-free Survival (DFS)
时间窗: 1 year
Percentage of participants that were disease-free survival (DFS) at 1 year post-transplant
次要结局
- Incidence of Grade II-IV and Grade III-IV Acute Graft Versus-host-disease (GVHD)(day 100)
- Treatment Related Mortality (TRM)(6 month, 1 and 2 year)
- Relapse Incidence(1 and 2 year)
- Incidence of Serious Fungal and Viral Infection(at day 100 and 1 year)