Phase 1 Trial for Patients With Advanced Hematologic Malignancies Undergoing Reduced Intensity Allogeneic HCT With a T-cell Depleted Graft With Infusion of Conventional T-cells and Regulatory T-cells
概览
- 阶段
- 1 期
- 干预措施
- Plerixafor
- 疾病 / 适应症
- Allogeneic Hematopoietic Cell Transplantation (HCT)
- 发起方
- Stanford University
- 入组人数
- 77
- 试验地点
- 1
- 主要终点
- Determine the overall survival (OS) post-HCT ( Arm-B)
- 状态
- 招募中
- 最后更新
- 24天前
概览
简要总结
Reduced intensity conditioning (RIC) has emerged and been increasingly adopted as a modality to allow preparative conditioning pre transplant to be tolerated by older adults or those patients that are otherwise unfit for myeloablative conditioning. In this study, we aim to use RIC followed by matched related/unrelated donor, 7/8 matched related/unrelated donor, or haploidentical donor peripheral blood stem cell transplantation. Standard strategies to control the alloreactivity following HCT utilize immunosuppressive or cytotoxic medications. In this study, we explore donor graft engineering to enrich for immmunoregulatory populations to facilitate post transplantation immune reconstitution while minimizing graft versus host disease (GVHD) with post-transplant immunosuppressive agents.
详细描述
The objectives for the study are listed below: Primary Objectives \*Determine the safety, and feasibility of administration of several dose combinations of conventional T-cells (Tcon) and regulatory T-cells (Treg) in subjects undergoing allogeneic hematopoietic cell transplantation (HCT) with related/unrelated HLA-matched or mismatched donors, or haploidentical donors with reduced intensity conditioning preparative regimen. Secondary Objectives * To determine the GVHD-free relapse-free survival (GRFS) post-HCT * To determine the overall survival (OS) post-HCT * To measure the incidence and severity of acute and chronic GVHD Exploratory Objectives * To measure the incidence of serious infections * To measure the incidence and timing of engraftment * To measure T cell immunity reconstitution parameters
研究者
入排标准
入选标准
- •Recipient Inclusion Criteria a. Patients with the following diseases that are histopathologically-confirmed are eligible
- •Acute myeloid, lymphoid, or mixed phenotype leukemia in complete remission (CR) or CR with incomplete hematologic recovery (CRi) or beyond first complete remission (CR1) without the presence of minimal residual disease
- •Acute myeloid, leukemia, or mixed phenotype leukemia that is either:
- •Not in morphologic CR with bone marrow infiltration by leukemic blasts of ≤10%, or
- •In morphologic CR with evidence of minimal residual disease positivity by either multiparametric flow cytometric analysis or by a nucleic acid-based technique
- •Primary refractory acute myeloid, lymphoid, or mixed phenotype leukemia
- •Chronic myelogenous leukemia (accelerated, blast or second chronic phase)
- •Myelodysplastic syndromes
- •Myeloproliferative syndromes b. Match to the patient as follows:
- •For Arm A1 (CLOSED):
排除标准
- •Recipient Exclusion Criteria
- •Seropositive for any of the following:
- •HIV antibodies; hepatitis B surface antigen (sAg); hepatitis C antibodies
- •Patients deemed candidates for fully myeloablative preparative conditioning regimens
- •d. Candidate for autologous transplant e. Hepatitis B or C with SGPT or SGOT \> 3 x ULN f. HIV-positive g. Active uncontrolled bacterial, viral or fungal infection, defined as currently taking antimicrobial therapy and progression of clinical symptoms. h. Uncontrolled CNS disease involvement i. Pregnant or a lactating female j. Positive serum or urine beta-HCG test in females of childbearing potential within 3 weeks of registration k. Psychosocial circumstances that preclude the patient being able to go through transplant or participate responsibly in follow-up care l. Known allergy or hypersensitivity to, or intolerance of, tacrolimus m. Positive anti-donor HLA antibodies against a mismatched allele in the selected donor determined by either:
- •A positive crossmatch of any titer; or
- •The presence of anti-donor HLA antibody to any HLA locus n. Any uncontrolled autoimmune disease requiring active immunosuppressive treatment o. Concurrent malignancies or active disease within 1 year, except nonmelanomatous skin cancers that have been curatively resected
- •Donor Exclusion Criteria
- •Evidence of active infection
- •Seropositive for HIV-1 or-2, HTLV-1 or -2
研究组 & 干预措施
Arm B: Haploidentical transplantation (closed)
Subjects without an identified matched related or matched unrelated donor will receive a haploidentical transplantation with reduced intensity preparative conditioning: -. Fludarabine (160 mg/m2) * Melphalan (100 mg/m2 * TBI (4Gy) Patients will receive GVHD prophylaxis with post-transplant cyclophosphamide and tacrolimus.
干预措施: Plerixafor
Arm A3: Fully (8/8) matched related/unrelated donor transplantation (closed)
Subjects will receive reduced intensity preparative chemotherapy conditioning for a matched related/ unrelated donor transplant: * Fludarabine (160 mg/m2) * Thiotepa (5 mg/kg) * TBI (2-3 Gy). All enrolled subjects will receive GVHD prophylaxis with single-agent tacrolimus.
干预措施: Thiotepa
Arm A1: Matched related/matched unrelated donor transplantation (closed)
Subjects will receive reduced intensity preparative chemotherapy conditioning for a matched related/ unrelated donor transplant:. * Fludarabine (160 mg/m2) * Melphalan (50 mg/m2) * TBI (4Gy) All enrolled subjects will receive GVHD prophylaxis with single-agent tacrolimus.
干预措施: Purified regulatory T-cells (Treg) plus CD34+ HSPC
Arm B: Haploidentical transplantation (closed)
Subjects without an identified matched related or matched unrelated donor will receive a haploidentical transplantation with reduced intensity preparative conditioning: -. Fludarabine (160 mg/m2) * Melphalan (100 mg/m2 * TBI (4Gy) Patients will receive GVHD prophylaxis with post-transplant cyclophosphamide and tacrolimus.
干预措施: Purified regulatory T-cells (Treg) plus CD34+ HSPC
Arm B: Haploidentical transplantation (closed)
Subjects without an identified matched related or matched unrelated donor will receive a haploidentical transplantation with reduced intensity preparative conditioning: -. Fludarabine (160 mg/m2) * Melphalan (100 mg/m2 * TBI (4Gy) Patients will receive GVHD prophylaxis with post-transplant cyclophosphamide and tacrolimus.
干预措施: CliniMACS CD34 Reagent System
Arm C1:7/8 mismatched related/unrelated donor transplantation (closed)
Subjects will receive reduced intensity preparative chemotherapy conditioning for a matched related/ unrelated donor transplant: * Fludarabine (160 mg/m2) * Thiotepa (10 mg/kg) * TBI (4 Gy) All enrolled subjects will receive GVHD prophylaxis with tacrolimus and mycophenolate mofetil (MMF).
干预措施: Purified regulatory T-cells (Treg) plus CD34+ HSPC
Arm A4: 8/8 mismatched related/unrelated donor transplantation
Subjects will receive reduced intensity preparative chemotherapy conditioning for a matched related/ unrelated donor transplant: * Fludarabine (160 mg/m2) * Thiotepa (7.5 mg/kg) * TBI (2-3 Gy) All enrolled subjects will receive GVHD prophylaxis with tacrolimus
干预措施: Purified regulatory T-cells (Treg) plus CD34+ HSPC
Arm C2: 7/8 mismatched related/unrelated donor transplantation
Subjects will receive reduced intensity preparative chemotherapy conditioning for a matched related/ unrelated donor transplant: * Fludarabine (160 mg/m2) * Thiotepa (5 mg/kg) * TBI (2-3 Gy) All enrolled subjects will receive GVHD prophylaxis with tacrolimus and ruxolitinib.
干预措施: Purified regulatory T-cells (Treg) plus CD34+ HSPC
Arm A2: Fully matched (8/8) related/unrelated donor transplantation (closed)
Subjects will receive reduced intensity preparative chemotherapy conditioning for a matched related/ unrelated donor transplant: * Fludarabine (160 mg/m2) * Thiotepa (10 mg/kg) * TBI (4Gy) All enrolled subjects will receive GVHD prophylaxis with single-agent tacrolimus.
干预措施: Purified regulatory T-cells (Treg) plus CD34+ HSPC
Arm A2: Fully matched (8/8) related/unrelated donor transplantation (closed)
Subjects will receive reduced intensity preparative chemotherapy conditioning for a matched related/ unrelated donor transplant: * Fludarabine (160 mg/m2) * Thiotepa (10 mg/kg) * TBI (4Gy) All enrolled subjects will receive GVHD prophylaxis with single-agent tacrolimus.
干预措施: Filgrastim granulocyte colony-stimulating factor (G-CSF) or equivalent
Arm A3: Fully (8/8) matched related/unrelated donor transplantation (closed)
Subjects will receive reduced intensity preparative chemotherapy conditioning for a matched related/ unrelated donor transplant: * Fludarabine (160 mg/m2) * Thiotepa (5 mg/kg) * TBI (2-3 Gy). All enrolled subjects will receive GVHD prophylaxis with single-agent tacrolimus.
干预措施: Purified regulatory T-cells (Treg) plus CD34+ HSPC
Arm A2: Fully matched (8/8) related/unrelated donor transplantation (closed)
Subjects will receive reduced intensity preparative chemotherapy conditioning for a matched related/ unrelated donor transplant: * Fludarabine (160 mg/m2) * Thiotepa (10 mg/kg) * TBI (4Gy) All enrolled subjects will receive GVHD prophylaxis with single-agent tacrolimus.
干预措施: Fludarabine
Arm A2: Fully matched (8/8) related/unrelated donor transplantation (closed)
Subjects will receive reduced intensity preparative chemotherapy conditioning for a matched related/ unrelated donor transplant: * Fludarabine (160 mg/m2) * Thiotepa (10 mg/kg) * TBI (4Gy) All enrolled subjects will receive GVHD prophylaxis with single-agent tacrolimus.
干预措施: Tacrolimus
Arm A4: 8/8 mismatched related/unrelated donor transplantation
Subjects will receive reduced intensity preparative chemotherapy conditioning for a matched related/ unrelated donor transplant: * Fludarabine (160 mg/m2) * Thiotepa (7.5 mg/kg) * TBI (2-3 Gy) All enrolled subjects will receive GVHD prophylaxis with tacrolimus
干预措施: Plerixafor
Arm A4: 8/8 mismatched related/unrelated donor transplantation
Subjects will receive reduced intensity preparative chemotherapy conditioning for a matched related/ unrelated donor transplant: * Fludarabine (160 mg/m2) * Thiotepa (7.5 mg/kg) * TBI (2-3 Gy) All enrolled subjects will receive GVHD prophylaxis with tacrolimus
干预措施: Tacrolimus
Arm A2: Fully matched (8/8) related/unrelated donor transplantation (closed)
Subjects will receive reduced intensity preparative chemotherapy conditioning for a matched related/ unrelated donor transplant: * Fludarabine (160 mg/m2) * Thiotepa (10 mg/kg) * TBI (4Gy) All enrolled subjects will receive GVHD prophylaxis with single-agent tacrolimus.
干预措施: Plerixafor
Arm A2: Fully matched (8/8) related/unrelated donor transplantation (closed)
Subjects will receive reduced intensity preparative chemotherapy conditioning for a matched related/ unrelated donor transplant: * Fludarabine (160 mg/m2) * Thiotepa (10 mg/kg) * TBI (4Gy) All enrolled subjects will receive GVHD prophylaxis with single-agent tacrolimus.
干预措施: Thiotepa
Arm A3: Fully (8/8) matched related/unrelated donor transplantation (closed)
Subjects will receive reduced intensity preparative chemotherapy conditioning for a matched related/ unrelated donor transplant: * Fludarabine (160 mg/m2) * Thiotepa (5 mg/kg) * TBI (2-3 Gy). All enrolled subjects will receive GVHD prophylaxis with single-agent tacrolimus.
干预措施: Tacrolimus
Arm A3: Fully (8/8) matched related/unrelated donor transplantation (closed)
Subjects will receive reduced intensity preparative chemotherapy conditioning for a matched related/ unrelated donor transplant: * Fludarabine (160 mg/m2) * Thiotepa (5 mg/kg) * TBI (2-3 Gy). All enrolled subjects will receive GVHD prophylaxis with single-agent tacrolimus.
干预措施: Fludarabine
Arm A3: Fully (8/8) matched related/unrelated donor transplantation (closed)
Subjects will receive reduced intensity preparative chemotherapy conditioning for a matched related/ unrelated donor transplant: * Fludarabine (160 mg/m2) * Thiotepa (5 mg/kg) * TBI (2-3 Gy). All enrolled subjects will receive GVHD prophylaxis with single-agent tacrolimus.
干预措施: Plerixafor
Arm A3: Fully (8/8) matched related/unrelated donor transplantation (closed)
Subjects will receive reduced intensity preparative chemotherapy conditioning for a matched related/ unrelated donor transplant: * Fludarabine (160 mg/m2) * Thiotepa (5 mg/kg) * TBI (2-3 Gy). All enrolled subjects will receive GVHD prophylaxis with single-agent tacrolimus.
干预措施: Filgrastim granulocyte colony-stimulating factor (G-CSF) or equivalent
Arm A4: 8/8 mismatched related/unrelated donor transplantation
Subjects will receive reduced intensity preparative chemotherapy conditioning for a matched related/ unrelated donor transplant: * Fludarabine (160 mg/m2) * Thiotepa (7.5 mg/kg) * TBI (2-3 Gy) All enrolled subjects will receive GVHD prophylaxis with tacrolimus
干预措施: Fludarabine
Arm C2: 7/8 mismatched related/unrelated donor transplantation
Subjects will receive reduced intensity preparative chemotherapy conditioning for a matched related/ unrelated donor transplant: * Fludarabine (160 mg/m2) * Thiotepa (5 mg/kg) * TBI (2-3 Gy) All enrolled subjects will receive GVHD prophylaxis with tacrolimus and ruxolitinib.
干预措施: Sirolimus
Arm A4: 8/8 mismatched related/unrelated donor transplantation
Subjects will receive reduced intensity preparative chemotherapy conditioning for a matched related/ unrelated donor transplant: * Fludarabine (160 mg/m2) * Thiotepa (7.5 mg/kg) * TBI (2-3 Gy) All enrolled subjects will receive GVHD prophylaxis with tacrolimus
干预措施: Thiotepa
Arm A4: 8/8 mismatched related/unrelated donor transplantation
Subjects will receive reduced intensity preparative chemotherapy conditioning for a matched related/ unrelated donor transplant: * Fludarabine (160 mg/m2) * Thiotepa (7.5 mg/kg) * TBI (2-3 Gy) All enrolled subjects will receive GVHD prophylaxis with tacrolimus
干预措施: Filgrastim granulocyte colony-stimulating factor (G-CSF) or equivalent
Arm C1:7/8 mismatched related/unrelated donor transplantation (closed)
Subjects will receive reduced intensity preparative chemotherapy conditioning for a matched related/ unrelated donor transplant: * Fludarabine (160 mg/m2) * Thiotepa (10 mg/kg) * TBI (4 Gy) All enrolled subjects will receive GVHD prophylaxis with tacrolimus and mycophenolate mofetil (MMF).
干预措施: Filgrastim granulocyte colony-stimulating factor (G-CSF) or equivalent
Arm C1:7/8 mismatched related/unrelated donor transplantation (closed)
Subjects will receive reduced intensity preparative chemotherapy conditioning for a matched related/ unrelated donor transplant: * Fludarabine (160 mg/m2) * Thiotepa (10 mg/kg) * TBI (4 Gy) All enrolled subjects will receive GVHD prophylaxis with tacrolimus and mycophenolate mofetil (MMF).
干预措施: Mycophenolate Mofetil (MMF)
Arm C2: 7/8 mismatched related/unrelated donor transplantation
Subjects will receive reduced intensity preparative chemotherapy conditioning for a matched related/ unrelated donor transplant: * Fludarabine (160 mg/m2) * Thiotepa (5 mg/kg) * TBI (2-3 Gy) All enrolled subjects will receive GVHD prophylaxis with tacrolimus and ruxolitinib.
干预措施: Filgrastim granulocyte colony-stimulating factor (G-CSF) or equivalent
Arm C2: 7/8 mismatched related/unrelated donor transplantation
Subjects will receive reduced intensity preparative chemotherapy conditioning for a matched related/ unrelated donor transplant: * Fludarabine (160 mg/m2) * Thiotepa (5 mg/kg) * TBI (2-3 Gy) All enrolled subjects will receive GVHD prophylaxis with tacrolimus and ruxolitinib.
干预措施: Thiotepa
Arm C2: 7/8 mismatched related/unrelated donor transplantation
Subjects will receive reduced intensity preparative chemotherapy conditioning for a matched related/ unrelated donor transplant: * Fludarabine (160 mg/m2) * Thiotepa (5 mg/kg) * TBI (2-3 Gy) All enrolled subjects will receive GVHD prophylaxis with tacrolimus and ruxolitinib.
干预措施: Ruxolitinib
Arm A1: Matched related/matched unrelated donor transplantation (closed)
Subjects will receive reduced intensity preparative chemotherapy conditioning for a matched related/ unrelated donor transplant:. * Fludarabine (160 mg/m2) * Melphalan (50 mg/m2) * TBI (4Gy) All enrolled subjects will receive GVHD prophylaxis with single-agent tacrolimus.
干预措施: Melphalan
Arm A1: Matched related/matched unrelated donor transplantation (closed)
Subjects will receive reduced intensity preparative chemotherapy conditioning for a matched related/ unrelated donor transplant:. * Fludarabine (160 mg/m2) * Melphalan (50 mg/m2) * TBI (4Gy) All enrolled subjects will receive GVHD prophylaxis with single-agent tacrolimus.
干预措施: Filgrastim granulocyte colony-stimulating factor (G-CSF) or equivalent
Arm B: Haploidentical transplantation (closed)
Subjects without an identified matched related or matched unrelated donor will receive a haploidentical transplantation with reduced intensity preparative conditioning: -. Fludarabine (160 mg/m2) * Melphalan (100 mg/m2 * TBI (4Gy) Patients will receive GVHD prophylaxis with post-transplant cyclophosphamide and tacrolimus.
干预措施: Filgrastim granulocyte colony-stimulating factor (G-CSF) or equivalent
Arm A1: Matched related/matched unrelated donor transplantation (closed)
Subjects will receive reduced intensity preparative chemotherapy conditioning for a matched related/ unrelated donor transplant:. * Fludarabine (160 mg/m2) * Melphalan (50 mg/m2) * TBI (4Gy) All enrolled subjects will receive GVHD prophylaxis with single-agent tacrolimus.
干预措施: Fludarabine
Arm A1: Matched related/matched unrelated donor transplantation (closed)
Subjects will receive reduced intensity preparative chemotherapy conditioning for a matched related/ unrelated donor transplant:. * Fludarabine (160 mg/m2) * Melphalan (50 mg/m2) * TBI (4Gy) All enrolled subjects will receive GVHD prophylaxis with single-agent tacrolimus.
干预措施: Tacrolimus
Arm A1: Matched related/matched unrelated donor transplantation (closed)
Subjects will receive reduced intensity preparative chemotherapy conditioning for a matched related/ unrelated donor transplant:. * Fludarabine (160 mg/m2) * Melphalan (50 mg/m2) * TBI (4Gy) All enrolled subjects will receive GVHD prophylaxis with single-agent tacrolimus.
干预措施: Plerixafor
Arm B: Haploidentical transplantation (closed)
Subjects without an identified matched related or matched unrelated donor will receive a haploidentical transplantation with reduced intensity preparative conditioning: -. Fludarabine (160 mg/m2) * Melphalan (100 mg/m2 * TBI (4Gy) Patients will receive GVHD prophylaxis with post-transplant cyclophosphamide and tacrolimus.
干预措施: Melphalan
Arm B: Haploidentical transplantation (closed)
Subjects without an identified matched related or matched unrelated donor will receive a haploidentical transplantation with reduced intensity preparative conditioning: -. Fludarabine (160 mg/m2) * Melphalan (100 mg/m2 * TBI (4Gy) Patients will receive GVHD prophylaxis with post-transplant cyclophosphamide and tacrolimus.
干预措施: Fludarabine
Arm B: Haploidentical transplantation (closed)
Subjects without an identified matched related or matched unrelated donor will receive a haploidentical transplantation with reduced intensity preparative conditioning: -. Fludarabine (160 mg/m2) * Melphalan (100 mg/m2 * TBI (4Gy) Patients will receive GVHD prophylaxis with post-transplant cyclophosphamide and tacrolimus.
干预措施: Tacrolimus
Arm B: Haploidentical transplantation (closed)
Subjects without an identified matched related or matched unrelated donor will receive a haploidentical transplantation with reduced intensity preparative conditioning: -. Fludarabine (160 mg/m2) * Melphalan (100 mg/m2 * TBI (4Gy) Patients will receive GVHD prophylaxis with post-transplant cyclophosphamide and tacrolimus.
干预措施: Cyclophosphamide
Arm C1:7/8 mismatched related/unrelated donor transplantation (closed)
Subjects will receive reduced intensity preparative chemotherapy conditioning for a matched related/ unrelated donor transplant: * Fludarabine (160 mg/m2) * Thiotepa (10 mg/kg) * TBI (4 Gy) All enrolled subjects will receive GVHD prophylaxis with tacrolimus and mycophenolate mofetil (MMF).
干预措施: Fludarabine
Arm C1:7/8 mismatched related/unrelated donor transplantation (closed)
Subjects will receive reduced intensity preparative chemotherapy conditioning for a matched related/ unrelated donor transplant: * Fludarabine (160 mg/m2) * Thiotepa (10 mg/kg) * TBI (4 Gy) All enrolled subjects will receive GVHD prophylaxis with tacrolimus and mycophenolate mofetil (MMF).
干预措施: Tacrolimus
Arm C1:7/8 mismatched related/unrelated donor transplantation (closed)
Subjects will receive reduced intensity preparative chemotherapy conditioning for a matched related/ unrelated donor transplant: * Fludarabine (160 mg/m2) * Thiotepa (10 mg/kg) * TBI (4 Gy) All enrolled subjects will receive GVHD prophylaxis with tacrolimus and mycophenolate mofetil (MMF).
干预措施: Plerixafor
Arm C1:7/8 mismatched related/unrelated donor transplantation (closed)
Subjects will receive reduced intensity preparative chemotherapy conditioning for a matched related/ unrelated donor transplant: * Fludarabine (160 mg/m2) * Thiotepa (10 mg/kg) * TBI (4 Gy) All enrolled subjects will receive GVHD prophylaxis with tacrolimus and mycophenolate mofetil (MMF).
干预措施: Thiotepa
Arm C2: 7/8 mismatched related/unrelated donor transplantation
Subjects will receive reduced intensity preparative chemotherapy conditioning for a matched related/ unrelated donor transplant: * Fludarabine (160 mg/m2) * Thiotepa (5 mg/kg) * TBI (2-3 Gy) All enrolled subjects will receive GVHD prophylaxis with tacrolimus and ruxolitinib.
干预措施: Fludarabine
Arm C2: 7/8 mismatched related/unrelated donor transplantation
Subjects will receive reduced intensity preparative chemotherapy conditioning for a matched related/ unrelated donor transplant: * Fludarabine (160 mg/m2) * Thiotepa (5 mg/kg) * TBI (2-3 Gy) All enrolled subjects will receive GVHD prophylaxis with tacrolimus and ruxolitinib.
干预措施: Tacrolimus
Arm C2: 7/8 mismatched related/unrelated donor transplantation
Subjects will receive reduced intensity preparative chemotherapy conditioning for a matched related/ unrelated donor transplant: * Fludarabine (160 mg/m2) * Thiotepa (5 mg/kg) * TBI (2-3 Gy) All enrolled subjects will receive GVHD prophylaxis with tacrolimus and ruxolitinib.
干预措施: Plerixafor
结局指标
主要结局
Determine the overall survival (OS) post-HCT ( Arm-B)
时间窗: 2 years
Overall survival is measured as number of participants alive. Alive at the time of last observation will be censored.
Determine the GVHD-free relapse-free survival (GRFS) post-HCT ( Arm-A)
时间窗: 12 months
Clinical effect will be assessed as graft vs host disease (GVHD)-free relapse free survival (GRFS), GVHD-free is defined as no GVHD symptoms, and relapse free survival is defined as survival at 12 months without relapse. The outcome will be measured in Arm A only.
Incidence of Grade III-IV acute GVHD
时间窗: At baseline, day +30, 60, 90, 180, year 1 and year 2
Acute GVHD will be staged and graded per Mount Sinai Acute GvHD International Consortium (MAGIC) Standardization criteria.
The incidence and timing of primary graft failure
时间窗: 2 years from the Day 0 (day of CD34+ peripheral blood stem cell infusion
Primary graft failure is defined as being alive with donor CD3 chimerism \<5% at day +30 after transplant without recovery of neutrophils (i.e. without achieving an absolute neutrophil count \[ANC\] ≥ 500/mm3 for 3 consecutive days) at Day+28
Donor CD3 chimerism at Day+60 post-HCT
时间窗: 2 years from the Day 0 (day of CD34+ peripheral blood stem cell infusion)
Defined as a percentage on donor CD3 cells chimerism at day +60 after transplantation.
次要结局
- Overall survival(12 months)
- Treatment-emergent adverse events (TEAs)(from Day 0 through 100 days)
- Acute GVHD (all grades)(from Day 0 through 100 days)
- GVHD-relapse-free survival(12 months)
- Secondary graft failure(from Day 0 through 100 days)
- Steroid-refractory acute GVHD(within 3-5 days of therapy onset)
- Non-relapse mortality (NRM)(12 months)
- Disease-free survival (DFS)(12 months)
- Chronic GVHD (limited or extensive)(from Day 0 through Year 2)