NCT03615105终止2 期
Allogeneic Hematopoietic Cell Transplantation Using α/β+ T-lymphocyte Depleted Grafts From HLA Mismatched Donors
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- the Number of Incidences of Grade 3-4 Acute GVHD
研究概览
简要总结
This study is being done to learn whether a new method to prevent rejection between the donor immune system and the patient's body is effective.
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 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with any of the following hematologic malignancies who are considered to be eligible for allogeneic transplantation:
- •Acute lymphoid leukemia (ALL) in first complete remission (CR1) with high risk for relapse including:
- •Detectable minimal residual disease by either multicolor flow cytometry or by genomic assay after initial induction therapy
- •t(9;22) or detected BCR-ABL1 translocation by genomic methodologies
- •BCR-ABL1-Like B-ALL [23] including mutations of IKZF1 or CRLF2
- •Translocations or mutations involving 11q23 (MLL) gene.
- •Hypodiploid karyotype
- •Deletion of 9p
- •Loss of 17p or TP53 mutation
- •T-lymphocyte lineage antigen expression (T-ALL)
- •Prior CNS or other extramedullary involvement
- •WBC count ≥ 100,000 cells/μL at diagnosis
- •Acute biphenotypic or bilineal leukemia in CR1
- •Acute myeloid leukemia (AML) in CR1 with
- •Detectable minimal residual disease (MRD) by either multicolor flow cytometry or by genomic assay after initial induction therapy
- •In the absence of MRD any intermediate or high risk features according to the European LeukemiaNet 2017 guidelines indlucing:
- •Mutated FL T3-ITD or FL T3-TKD
- •Cytogenetic abnormalities not classified as favorable
- •Cytogenetic abnormalities associated with myelodysplastic syndrome including abnormalities of chromosome 5, 7, or 17p
- •Complex karyotype or monosomal karyotype
- •t(9;11)(p21.1;q23.3); MLL-KMT2A or other rearrangements of KMT2A
- •t(9;11); BCR-ABL1
- •Inversions or translocations of chromosome 3
- •T(6;9)(p23;q34.1); DEK-NUP214
- •Somatic mutation of RUNX1, ASX1 or TP53
- •Extramedullary involvement
- •WBC count ≥100,000 cells/μL at diagnosis
- •Relapsed acute leukemia with ≤ 5% blasts in the bone marrow prior to transplantation (i.e. CR2 or greater).
- •Myelodysplastic syndrome, myeloproliferative neoplasms, or MDS/MPN overlap syndrome with ≤ 10% blasts and at least one of the following:
- •Revised International Prognostic Scoring System risk score of INT, HIGH, or VERY HIGH at the time of transplant evaluation.
- •Life-threatening cytopenias
- •Karyotype or genomic changes that indicate high risk for progression to acute myelogenous leukemia, including abnormalities of chromosome 7 or 3, mutations of TP53, or complex or monosomal karyotype.
- •Therapy related disease or disease evolving from other malignant processes.
- •Chronic myelomonocytic leukemia (CMML) with ≤ 10% blasts prior to transplantation.
- •Chronic myeloid leukemia (CML) meeting one of the following criteria:
- •Failed or are intolerant to BCR-ABL tyrosine kinase inhibitors.
- •CML with BCR-ABL mutation consistent with poor response to tyrosine kinase inhibition (e.g. T351I mutation).
- •CML with accelerated or blast phase with <10% blasts after therapy.
- •Chronic lymphocytic leukemia (CLL) with high risk disease as defined by the EBMT consensus criteria
- •Hodgkin lymphoma meeting both of the following criteria:
- •Responding to therapy prior to enrollment
- •Relapse after autologous bone marrow transplant or are ineligible for autologous bone marrow transplant.
- •°Non-Hodgkin lymphoma meeting both of the following criteria:
- •Responding to therapy prior to enrollment.
- •Relapse after prior autologous bone marrow transplant or are ineligible for autologous bone marrow transplant.
- •Patients aged from birth through 65 years old are eligible.
- •Patients must have Karnofsky/Lanksy performance status ≥70%.
- •Cardiac left ventricular ejection fraction ≥50% at rest.
- •Serum bilirubin ≤ 2 mg/dL. Patients with Gilbert's disease or ongoing hemolytic anemia are acceptable if the direct bilirubin is ≤ 2 mg/dL.
- •AST and ALT ≤ 2.5 x ULN unless thought to be disease related
- 另有 2 项未显示
排除标准
- •Persons with a HLA matched sibling donor or a 8/8 allele level HLA-matched unrelated donor.
- •Female patients who are pregnant or breast-feeding.
- •Persons with an infection that is not responding to antimicrobial therapy.
- •Persons who are seropositive for HIV.
- •Persons with active/detectable central nervous system malignancy.
- •Persons who do not meet the age and organ function criteria specified above.
- •Presence of psychiatric or neurologic disease, or lack of social support that limits the patient's ability to comply with the treatment protocol including supportive care, followup, and research tests.
- •Prior allogeneic hematopoietic cell transplantation are ineligible.
- •Patients with history of other malignancy within 5 years of study therapy are ineligible with the following exceptions: Low grade prostate cancer (Gleason's ≤6) treated with curative intent, breast ductal carcinoma in situ treated with curative intent, or nonmelanomatous skin carcinomas.
- •Donor Inclusion and Exclusion Criteria:
- •Partially HLA-matched unrelated volunteers (allele level matched at 6-7 of 8 HLA loci: -A, -B, -C, and -DRB1) are eligible.
- •Related, haploidentical donors are eligible.
- •Able to provide informed consent to the donation process
- •Meet standard criteria for donor collection as defined by the National Marrow Donor Program Guidelines.
研究组 & 干预措施
Radiation, Thiotepa & Cyclophosphamide
Experimental
干预措施: Hyperfractionated total body irradiation (Radiation)
Radiation, Thiotepa & Cyclophosphamide
Experimental
干预措施: Thiotepa (Drug)
Radiation, Thiotepa & Cyclophosphamide
Experimental
干预措施: Cyclophosphamide (Drug)
Radiation, Thiotepa & Cyclophosphamide
Experimental
干预措施: HPC(A) stem cell allograft (Procedure)
Radiation, Thiotepa & Cyclophosphamide
Experimental
干预措施: Rituximab (Drug)
Radiation, Thiotepa & Cyclophosphamide
Experimental
干预措施: Rabbit antithymocyte globulin (Device)
Busulfan, Fludarabine & Melphalan
Experimental
干预措施: Busulfan (Drug)
Busulfan, Fludarabine & Melphalan
Experimental
干预措施: Fludarabine (Drug)
Busulfan, Fludarabine & Melphalan
Experimental
干预措施: Melphalan (Drug)
Busulfan, Fludarabine & Melphalan
Experimental
干预措施: HPC(A) stem cell allograft (Procedure)
Busulfan, Fludarabine & Melphalan
Experimental
干预措施: Rituximab (Drug)
Busulfan, Fludarabine & Melphalan
Experimental
干预措施: Rabbit antithymocyte globulin (Device)
Clofarabine, Thiotepa & Melphalan
Experimental
干预措施: Thiotepa (Drug)
Clofarabine, Thiotepa & Melphalan
Experimental
干预措施: Melphalan (Drug)
Clofarabine, Thiotepa & Melphalan
Experimental
干预措施: Clofarabine (Drug)
Clofarabine, Thiotepa & Melphalan
Experimental
干预措施: HPC(A) stem cell allograft (Procedure)
Clofarabine, Thiotepa & Melphalan
Experimental
干预措施: Rituximab (Drug)
Clofarabine, Thiotepa & Melphalan
Experimental
干预措施: Rabbit antithymocyte globulin (Device)
结局指标
主要结局
the Number of Incidences of Grade 3-4 Acute GVHD
时间窗: 2 years
The intervention will be considered unpromising if the rate of GVHD is greater than 40% and promising if the rate is 20% or less. Number of participants with and without SAE will be evaluated.
次要结局
未报告次要终点
研究者
研究点 (1)
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