A Phase II Study of Reduced Dose Post Transplantation Cyclophosphamide as GvHD Prophylaxis in Adult Patients With Hematologic Malignancies Receiving HLA-Mismatched Unrelated Donor Peripheral Blood Stem Cell Transplantation
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 313
- 试验地点
- 32
- 主要终点
- Infection Free Survival
研究概览
简要总结
The goal of this clinical trial is to determine the effectiveness of Reduced Dose Post-Transplant Cyclophosphamide (PTCy) in patients with hematologic malignancies after receiving an HLA-Mismatched Unrelated Donor (MMUD) . The main question[s] it aims to answer are:
- Does a reduced dose of PTCy reduce the occurrence of infections in the first 100 days after transplant?
- Does a reduced dose of PTCy maintain the same level of protection against Graft Versus Host Disease (GvHD) as the standard dose of PTCy?
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Stratum 1 Recipient Inclusion Criteria:
- •Age ≥ 18 years and < 66 years (chemotherapy-based conditioning) or < 61 years (total body irradiation [TBI]-based conditioning) at the time of signing informed consent
- •Patient or legally authorized representative has the ability to provide informed consent according to the applicable regulatory and institutional requirements.
- •Stated willingness to comply with all study procedures and availability for the duration of the study.
- •Planned MAC regimen as defined per study protocol
- •Available partially HLA-MMUD (4/8-7/8 at HLA-A, -B, -C, and -DRB1 is required) with age ≥ 18 and ≤ 40 years (≤ 35 preferred).
- •Product planned for infusion is MMUD T-cell replete PBSC allograft
- •The presence of prior malignancy will not be used to calculate HCT-CI for this trial to allow for the inclusion of patients with secondary or therapy-related AML or MDS.
- •One of the following diagnoses:
- •Acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), or other acute leukemia in 1st remission or beyond with ≤ 5% marrow blasts and no circulating blasts or evidence of extra-medullary disease. Documentation of bone marrow assessment will be accepted within 45 days prior to the anticipated start of conditioning.
- •Patients with MDS with no circulating blasts and with < 10% blasts in the bone marrow (higher blast percentage allowed in MDS due to lack of differences in outcomes with < 5% or 5-10% blasts in MDS). Documentation of bone marrow assessment will be accepted within 45 days prior to the anticipated start of conditioning.
- •Cardiac function: Left ventricular ejection fraction ≥ 45% based on most recent echocardiogram or multi-gated acquisition scan (MUGA) results.
- •Estimated creatinine clearance ≥ 45mL/min calculated by equation.
- •Pulmonary function: diffusing capacity of the lungs for carbon monoxide (DLCO) corrected for hemoglobin > 50% and forced expiratory volume in first second (FEV1) predicted > 50% based on most recent pulmonary function test (PFT) results
- •Liver function acceptable per local institutional guidelines
- •KPS of ≥ 70%
- •Stratum 2 Recipient Inclusion Criteria:
- •Age ≥18 years at the time of signing informed consent
- •Patient or legally authorized representative has the ability to provide informed consent according to the applicable regulatory and local institutional requirements.
- •Stated willingness to comply with all study procedures and availability for the duration of the study.
- •Planned NMA/RIC regimen per study protocol
- •Available partially HLA-MMUD (4/8-7/8 at HLA-A, -B, -C, and -DRB1 is required) with age ≥ 18 and ≤ 40 years (≤ 35 preferred).
- •Product planned for infusion is MMUD T-cell replete PBSC allograft
- •One of the following diagnoses:
- •Patients with acute leukemia or chronic myeloid leukemia (CML) with no circulating blasts, no evidence of extramedullary disease, and with < 5% blasts in the bone marrow.
- •Documentation of bone marrow assessment will be accepted within 45 days prior to the anticipated start of conditioning.
- •Patients with MDS with no circulating blasts and with < 10% blasts in the bone marrow (higher blast percentage allowed in MDS due to lack of differences in outcomes with < 5% or 5-10% blasts in MDS.) Documentation of bone marrow assessment will be accepted within 45 days prior to the anticipated start of conditioning.
- •Patients with chronic lymphocytic leukemia (CLL) or other leukemias (including prolymphocytic leukemia) with chemosensitive disease at time of transplantation
- •Higher risk CMML according to CMML-specific prognostic scoring system or high risk MDS/MPN not otherwise specified are eligible, provided there is no evidence of high-grade bone marrow fibrosis or massive splenomegaly at the time of enrollment.
- •Patients with lymphoma with chemosensitive disease at the time of transplantation
- •Cardiac function: Left ventricular ejection fraction ≥ 40% based on most recent echocardiogram or MUGA results with no clinical evidence of heart failure
- •Estimated creatinine clearance ≥ 45mL/min calculated by equation
- •Pulmonary function: DLCO corrected for hemoglobin > 50% and FEV1 predicted >50% based on most recent PFT results
- •Liver function acceptable per local institutional guidelines
- •KPS of ≥ 60%
- •Stratum 3 Recipient Inclusion Criteria:
- •Age ≥18 years at the time of signing informed consent
- •Patient or legally authorized representative has the ability to provide informed consent according to the applicable regulatory and local institutional requirements.
- •Stated willingness to comply with all study procedures and availability for the duration of the study.
- •Planned NMA/RIC regimen per study protocol
- •Available partially HLA-MMUD (4/8-7/8 at HLA-A, -B, -C, and -DRB1 is required) with age ≥ 18 and ≤ 40 years (≤ 35 preferred).
- •Product planned for infusion is MMUD T-cell replete PBSC allograft
- •Diagnosis of primary myelofibrosis with risk features making them eligible for HCT. Myelofibrosis secondary to essential thrombocythemia, polycythemia vera, or MDS with grade 4 fibrosis are also eligible. Patients with a myelofibrosis diagnosis require sponsor approval before enrolling.
- •Cardiac function: Left ventricular ejection fraction ≥ 40% based on most recent echocardiogram or MUGA results with no clinical evidence of heart failure
- •Estimated creatinine clearance ≥ 45 mL/min calculated by equation
- •Pulmonary function: DLCO corrected for hemoglobin > 50% and FEV1 predicted >50% based on most recent PFT results
- •Liver function acceptable per local institutional guidelines
- •KPS of ≥ 60%
- •Donor Inclusion Criteria (note: donors are not research subjects):
- •Must be unrelated to the subject and high-resolution HLA-matched at 4/8, 5/8, 6/8, or 7/8 (HLA-A, -B, -C, and -DRB
- 另有 6 项未显示
排除标准
- •(Strata 1, 2, and 3):
- •Suitable HLA-matched related or 8/8 high-resolution matched unrelated donor available
- •Subject unwilling or unable to give informed consent, or unable to comply with the protocol including required follow-up and testing
- •Subjects with a prior allogeneic transplant
- •Subjects with an autologous transplant within the past 3 months
- •Females who are breast-feeding or pregnant
- •Uncontrolled bacterial, viral, or fungal infection at the time of the transplant preparative regimen
- •Concurrent enrollment on a preventative GvHD and/or infectious disease prevention clinical trial.
- •Subjects who undergo desensitization to reduce anti-donor HLA antibody levels prior to transplant.
- •Patients who are HIV+ with persistently positive viral load. HIV-infected patients on effective anti-retroviral therapy (ART) with undetectable viral load within 6 months are eligible for this trial. Patients with well controlled HIV are eligible provided resistance panels are negative, the patient is compliant with ART, and their disease remains well controlled.
- •Donor Exclusion Criteria:
- •Donor unwilling or unable to donate.
- •Recipient positive for HLA antibodies against a mismatched HLA in the selected donor determined by the presence of donor specific HLA antibodies (DSA) to any mismatched HLA allele/antigen at any of the following loci (HLA-A, -B, -C, -DRB1, DRB3, DRB4, DRB5, -DQA1, - DQB1, -DPA1, -DPB1) with median fluorescence intensity (MFI) >3000 by microarray-based single antigen bead testing. In patients receiving red blood cell or platelet transfusions, DSA evaluation must be performed or repeated post-transfusion and prior to donor mobilization and initiation of recipient preparative regimen.
研究组 & 干预措施
Regimen A (MAC: Busulfan and Fludarabine, PBSC HCT; Reduce Dose PTCy
Patients Receive:
Patients receive:
Busulfan (≥ 9 mg/kg total dose) IV or PO on days -6 to -3 Fludarabine (150 mg/m2 total dose) IV on days -6 to -2
Patients receive a peripheral blood stem cell (PBSC) graft infusion from a mismatched unrelated donor on Day 0.
Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.
First 20 patients with a 4-6/8 mismatched unrelated donor will receive an alternate dose of post-transplant cyclophosphamide of 37.5 mg/kg on Days 3 and Day 4 post-transplant.
干预措施: PBSC Hematopoietic Stem Cell Transplantation (HSCT) (Procedure)
Regimen A (MAC: Busulfan and Fludarabine, PBSC HCT; Reduce Dose PTCy
Patients Receive:
Patients receive:
Busulfan (≥ 9 mg/kg total dose) IV or PO on days -6 to -3 Fludarabine (150 mg/m2 total dose) IV on days -6 to -2
Patients receive a peripheral blood stem cell (PBSC) graft infusion from a mismatched unrelated donor on Day 0.
Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.
First 20 patients with a 4-6/8 mismatched unrelated donor will receive an alternate dose of post-transplant cyclophosphamide of 37.5 mg/kg on Days 3 and Day 4 post-transplant.
干预措施: Patient Reported Outcomes (Other)
Regimen B (MAC: Fludarabine and TBI, PBSC HCT; Reduce Dose PTCy
Patients receive:
Fludarabine (90 mg/m2 total dose) IV on days -7 to -5 Total body irradiation (TBI) (1200 cGy total dose) on days -4 to -1
Patients receive a peripheral blood stem cell (PBSC) graft infusion from a mismatched unrelated donor on Day 0.
Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.
First 20 patients with a 4-6/8 mismatched unrelated donor will receive an alternate dose of post-transplant cyclophosphamide of 37.5 mg/kg on Days 3 and Day 4 post-transplant.
干预措施: Patient Reported Outcomes (Other)
Regimen B (MAC: Fludarabine and TBI, PBSC HCT; Reduce Dose PTCy
Patients receive:
Fludarabine (90 mg/m2 total dose) IV on days -7 to -5 Total body irradiation (TBI) (1200 cGy total dose) on days -4 to -1
Patients receive a peripheral blood stem cell (PBSC) graft infusion from a mismatched unrelated donor on Day 0.
Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.
First 20 patients with a 4-6/8 mismatched unrelated donor will receive an alternate dose of post-transplant cyclophosphamide of 37.5 mg/kg on Days 3 and Day 4 post-transplant.
干预措施: Total-body irradiation (Radiation)
Regimen C (RIC: Fludarabine and Busulfan; PBSCT HCT; Reduced Dose PTCy
Patients receive:
Fludarabine (150-180 mg/m2 total dose) IV on days -6 to -2 Busulfan (less than or equal to 8 mg/kg PO or 6.4 mg/kg IV) on days -5 and -4
Patients receive a peripheral blood stem cell (PBSC) graft infusion from a mismatched unrelated donor on Day 0.
Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.
First 20 patients with a 4-6/8 mismatched unrelated donor will receive an alternate dose of post-transplant cyclophosphamide of 37.5 mg/kg on Days 3 and Day 4 post-transplant.
干预措施: PBSC Hematopoietic Stem Cell Transplantation (HSCT) (Procedure)
Regimen C (RIC: Fludarabine and Busulfan; PBSCT HCT; Reduced Dose PTCy
Patients receive:
Fludarabine (150-180 mg/m2 total dose) IV on days -6 to -2 Busulfan (less than or equal to 8 mg/kg PO or 6.4 mg/kg IV) on days -5 and -4
Patients receive a peripheral blood stem cell (PBSC) graft infusion from a mismatched unrelated donor on Day 0.
Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.
First 20 patients with a 4-6/8 mismatched unrelated donor will receive an alternate dose of post-transplant cyclophosphamide of 37.5 mg/kg on Days 3 and Day 4 post-transplant.
干预措施: Patient Reported Outcomes (Other)
Regimen D (RIC: Fludarabine and Melphalan; PBSCT HCT; Reduced Dose PTCy
Patients receive:
Fludarabine (125-150 mg/m2 total dose) IV on days -7 to -3 Melphalan (100-140 mg/m2) IV on day -1
Patients receive a PBSC graft infusion from a mismatched unrelated donor on Day 0.
Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.
First 20 patients with a 4-6/8 mismatched unrelated donor will receive an alternate dose of post-transplant cyclophosphamide of 37.5 mg/kg on Days 3 and Day 4 post-transplant.
干预措施: PBSC Hematopoietic Stem Cell Transplantation (HSCT) (Procedure)
Regimen D (RIC: Fludarabine and Melphalan; PBSCT HCT; Reduced Dose PTCy
Patients receive:
Fludarabine (125-150 mg/m2 total dose) IV on days -7 to -3 Melphalan (100-140 mg/m2) IV on day -1
Patients receive a PBSC graft infusion from a mismatched unrelated donor on Day 0.
Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.
First 20 patients with a 4-6/8 mismatched unrelated donor will receive an alternate dose of post-transplant cyclophosphamide of 37.5 mg/kg on Days 3 and Day 4 post-transplant.
干预措施: Patient Reported Outcomes (Other)
Regimen E (NMA: Fludarabine, Cyclophosphamide, and TBI; PBSCT HCT; Reduced Dose PTCy
Patients receive:
Fludarabine (150mg/m2 total dose) IV on days -6 to -2 Cyclophosphamide (29-50mg/kg) IV on days -6 and -5 TBI (200cGy) on day -1
Patients receive a PBSC graft infusion from a mismatched unrelated donor on Day 0.
Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.
First 20 patients with a 4-6/8 mismatched unrelated donor will receive an alternate dose of post-transplant cyclophosphamide of 37.5 mg/kg on Days 3 and Day 4 post-transplant.
干预措施: PBSC Hematopoietic Stem Cell Transplantation (HSCT) (Procedure)
Regimen D (RIC: Fludarabine and Melphalan; PBSCT HCT; Reduced Dose PTCy
Patients receive:
Fludarabine (125-150 mg/m2 total dose) IV on days -7 to -3 Melphalan (100-140 mg/m2) IV on day -1
Patients receive a PBSC graft infusion from a mismatched unrelated donor on Day 0.
Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.
First 20 patients with a 4-6/8 mismatched unrelated donor will receive an alternate dose of post-transplant cyclophosphamide of 37.5 mg/kg on Days 3 and Day 4 post-transplant.
干预措施: Post-Transplant Cyclophosphamide (Drug)
Regimen E (NMA: Fludarabine, Cyclophosphamide, and TBI; PBSCT HCT; Reduced Dose PTCy
Patients receive:
Fludarabine (150mg/m2 total dose) IV on days -6 to -2 Cyclophosphamide (29-50mg/kg) IV on days -6 and -5 TBI (200cGy) on day -1
Patients receive a PBSC graft infusion from a mismatched unrelated donor on Day 0.
Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.
First 20 patients with a 4-6/8 mismatched unrelated donor will receive an alternate dose of post-transplant cyclophosphamide of 37.5 mg/kg on Days 3 and Day 4 post-transplant.
干预措施: Mesna (Drug)
Regimen B (MAC: Fludarabine and TBI, PBSC HCT; Reduce Dose PTCy
Patients receive:
Fludarabine (90 mg/m2 total dose) IV on days -7 to -5 Total body irradiation (TBI) (1200 cGy total dose) on days -4 to -1
Patients receive a peripheral blood stem cell (PBSC) graft infusion from a mismatched unrelated donor on Day 0.
Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.
First 20 patients with a 4-6/8 mismatched unrelated donor will receive an alternate dose of post-transplant cyclophosphamide of 37.5 mg/kg on Days 3 and Day 4 post-transplant.
干预措施: PBSC Hematopoietic Stem Cell Transplantation (HSCT) (Procedure)
Regimen E (NMA: Fludarabine, Cyclophosphamide, and TBI; PBSCT HCT; Reduced Dose PTCy
Patients receive:
Fludarabine (150mg/m2 total dose) IV on days -6 to -2 Cyclophosphamide (29-50mg/kg) IV on days -6 and -5 TBI (200cGy) on day -1
Patients receive a PBSC graft infusion from a mismatched unrelated donor on Day 0.
Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.
First 20 patients with a 4-6/8 mismatched unrelated donor will receive an alternate dose of post-transplant cyclophosphamide of 37.5 mg/kg on Days 3 and Day 4 post-transplant.
干预措施: Patient Reported Outcomes (Other)
Regimen E (NMA: Fludarabine, Cyclophosphamide, and TBI; PBSCT HCT; Reduced Dose PTCy
Patients receive:
Fludarabine (150mg/m2 total dose) IV on days -6 to -2 Cyclophosphamide (29-50mg/kg) IV on days -6 and -5 TBI (200cGy) on day -1
Patients receive a PBSC graft infusion from a mismatched unrelated donor on Day 0.
Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.
First 20 patients with a 4-6/8 mismatched unrelated donor will receive an alternate dose of post-transplant cyclophosphamide of 37.5 mg/kg on Days 3 and Day 4 post-transplant.
干预措施: Total-body irradiation (Radiation)
Regimen A (MAC: Busulfan and Fludarabine, PBSC HCT; Reduce Dose PTCy
Patients Receive:
Patients receive:
Busulfan (≥ 9 mg/kg total dose) IV or PO on days -6 to -3 Fludarabine (150 mg/m2 total dose) IV on days -6 to -2
Patients receive a peripheral blood stem cell (PBSC) graft infusion from a mismatched unrelated donor on Day 0.
Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.
First 20 patients with a 4-6/8 mismatched unrelated donor will receive an alternate dose of post-transplant cyclophosphamide of 37.5 mg/kg on Days 3 and Day 4 post-transplant.
干预措施: Mycophenolate Mofetil (Drug)
Regimen A (MAC: Busulfan and Fludarabine, PBSC HCT; Reduce Dose PTCy
Patients Receive:
Patients receive:
Busulfan (≥ 9 mg/kg total dose) IV or PO on days -6 to -3 Fludarabine (150 mg/m2 total dose) IV on days -6 to -2
Patients receive a peripheral blood stem cell (PBSC) graft infusion from a mismatched unrelated donor on Day 0.
Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.
First 20 patients with a 4-6/8 mismatched unrelated donor will receive an alternate dose of post-transplant cyclophosphamide of 37.5 mg/kg on Days 3 and Day 4 post-transplant.
干预措施: Busulfan (Drug)
Regimen A (MAC: Busulfan and Fludarabine, PBSC HCT; Reduce Dose PTCy
Patients Receive:
Patients receive:
Busulfan (≥ 9 mg/kg total dose) IV or PO on days -6 to -3 Fludarabine (150 mg/m2 total dose) IV on days -6 to -2
Patients receive a peripheral blood stem cell (PBSC) graft infusion from a mismatched unrelated donor on Day 0.
Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.
First 20 patients with a 4-6/8 mismatched unrelated donor will receive an alternate dose of post-transplant cyclophosphamide of 37.5 mg/kg on Days 3 and Day 4 post-transplant.
干预措施: Post-Transplant Cyclophosphamide (Drug)
Regimen A (MAC: Busulfan and Fludarabine, PBSC HCT; Reduce Dose PTCy
Patients Receive:
Patients receive:
Busulfan (≥ 9 mg/kg total dose) IV or PO on days -6 to -3 Fludarabine (150 mg/m2 total dose) IV on days -6 to -2
Patients receive a peripheral blood stem cell (PBSC) graft infusion from a mismatched unrelated donor on Day 0.
Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.
First 20 patients with a 4-6/8 mismatched unrelated donor will receive an alternate dose of post-transplant cyclophosphamide of 37.5 mg/kg on Days 3 and Day 4 post-transplant.
干预措施: Fludarabine (Drug)
Regimen A (MAC: Busulfan and Fludarabine, PBSC HCT; Reduce Dose PTCy
Patients Receive:
Patients receive:
Busulfan (≥ 9 mg/kg total dose) IV or PO on days -6 to -3 Fludarabine (150 mg/m2 total dose) IV on days -6 to -2
Patients receive a peripheral blood stem cell (PBSC) graft infusion from a mismatched unrelated donor on Day 0.
Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.
First 20 patients with a 4-6/8 mismatched unrelated donor will receive an alternate dose of post-transplant cyclophosphamide of 37.5 mg/kg on Days 3 and Day 4 post-transplant.
干预措施: Tacrolimus (Drug)
Regimen B (MAC: Fludarabine and TBI, PBSC HCT; Reduce Dose PTCy
Patients receive:
Fludarabine (90 mg/m2 total dose) IV on days -7 to -5 Total body irradiation (TBI) (1200 cGy total dose) on days -4 to -1
Patients receive a peripheral blood stem cell (PBSC) graft infusion from a mismatched unrelated donor on Day 0.
Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.
First 20 patients with a 4-6/8 mismatched unrelated donor will receive an alternate dose of post-transplant cyclophosphamide of 37.5 mg/kg on Days 3 and Day 4 post-transplant.
干预措施: Fludarabine (Drug)
Regimen B (MAC: Fludarabine and TBI, PBSC HCT; Reduce Dose PTCy
Patients receive:
Fludarabine (90 mg/m2 total dose) IV on days -7 to -5 Total body irradiation (TBI) (1200 cGy total dose) on days -4 to -1
Patients receive a peripheral blood stem cell (PBSC) graft infusion from a mismatched unrelated donor on Day 0.
Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.
First 20 patients with a 4-6/8 mismatched unrelated donor will receive an alternate dose of post-transplant cyclophosphamide of 37.5 mg/kg on Days 3 and Day 4 post-transplant.
干预措施: Post-Transplant Cyclophosphamide (Drug)
Regimen B (MAC: Fludarabine and TBI, PBSC HCT; Reduce Dose PTCy
Patients receive:
Fludarabine (90 mg/m2 total dose) IV on days -7 to -5 Total body irradiation (TBI) (1200 cGy total dose) on days -4 to -1
Patients receive a peripheral blood stem cell (PBSC) graft infusion from a mismatched unrelated donor on Day 0.
Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.
First 20 patients with a 4-6/8 mismatched unrelated donor will receive an alternate dose of post-transplant cyclophosphamide of 37.5 mg/kg on Days 3 and Day 4 post-transplant.
干预措施: Tacrolimus (Drug)
Regimen B (MAC: Fludarabine and TBI, PBSC HCT; Reduce Dose PTCy
Patients receive:
Fludarabine (90 mg/m2 total dose) IV on days -7 to -5 Total body irradiation (TBI) (1200 cGy total dose) on days -4 to -1
Patients receive a peripheral blood stem cell (PBSC) graft infusion from a mismatched unrelated donor on Day 0.
Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.
First 20 patients with a 4-6/8 mismatched unrelated donor will receive an alternate dose of post-transplant cyclophosphamide of 37.5 mg/kg on Days 3 and Day 4 post-transplant.
干预措施: Mycophenolate Mofetil (Drug)
Regimen C (RIC: Fludarabine and Busulfan; PBSCT HCT; Reduced Dose PTCy
Patients receive:
Fludarabine (150-180 mg/m2 total dose) IV on days -6 to -2 Busulfan (less than or equal to 8 mg/kg PO or 6.4 mg/kg IV) on days -5 and -4
Patients receive a peripheral blood stem cell (PBSC) graft infusion from a mismatched unrelated donor on Day 0.
Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.
First 20 patients with a 4-6/8 mismatched unrelated donor will receive an alternate dose of post-transplant cyclophosphamide of 37.5 mg/kg on Days 3 and Day 4 post-transplant.
干预措施: Busulfan (Drug)
Regimen C (RIC: Fludarabine and Busulfan; PBSCT HCT; Reduced Dose PTCy
Patients receive:
Fludarabine (150-180 mg/m2 total dose) IV on days -6 to -2 Busulfan (less than or equal to 8 mg/kg PO or 6.4 mg/kg IV) on days -5 and -4
Patients receive a peripheral blood stem cell (PBSC) graft infusion from a mismatched unrelated donor on Day 0.
Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.
First 20 patients with a 4-6/8 mismatched unrelated donor will receive an alternate dose of post-transplant cyclophosphamide of 37.5 mg/kg on Days 3 and Day 4 post-transplant.
干预措施: Fludarabine (Drug)
Regimen C (RIC: Fludarabine and Busulfan; PBSCT HCT; Reduced Dose PTCy
Patients receive:
Fludarabine (150-180 mg/m2 total dose) IV on days -6 to -2 Busulfan (less than or equal to 8 mg/kg PO or 6.4 mg/kg IV) on days -5 and -4
Patients receive a peripheral blood stem cell (PBSC) graft infusion from a mismatched unrelated donor on Day 0.
Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.
First 20 patients with a 4-6/8 mismatched unrelated donor will receive an alternate dose of post-transplant cyclophosphamide of 37.5 mg/kg on Days 3 and Day 4 post-transplant.
干预措施: Post-Transplant Cyclophosphamide (Drug)
Regimen C (RIC: Fludarabine and Busulfan; PBSCT HCT; Reduced Dose PTCy
Patients receive:
Fludarabine (150-180 mg/m2 total dose) IV on days -6 to -2 Busulfan (less than or equal to 8 mg/kg PO or 6.4 mg/kg IV) on days -5 and -4
Patients receive a peripheral blood stem cell (PBSC) graft infusion from a mismatched unrelated donor on Day 0.
Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.
First 20 patients with a 4-6/8 mismatched unrelated donor will receive an alternate dose of post-transplant cyclophosphamide of 37.5 mg/kg on Days 3 and Day 4 post-transplant.
干预措施: Tacrolimus (Drug)
Regimen C (RIC: Fludarabine and Busulfan; PBSCT HCT; Reduced Dose PTCy
Patients receive:
Fludarabine (150-180 mg/m2 total dose) IV on days -6 to -2 Busulfan (less than or equal to 8 mg/kg PO or 6.4 mg/kg IV) on days -5 and -4
Patients receive a peripheral blood stem cell (PBSC) graft infusion from a mismatched unrelated donor on Day 0.
Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.
First 20 patients with a 4-6/8 mismatched unrelated donor will receive an alternate dose of post-transplant cyclophosphamide of 37.5 mg/kg on Days 3 and Day 4 post-transplant.
干预措施: Mycophenolate Mofetil (Drug)
Regimen D (RIC: Fludarabine and Melphalan; PBSCT HCT; Reduced Dose PTCy
Patients receive:
Fludarabine (125-150 mg/m2 total dose) IV on days -7 to -3 Melphalan (100-140 mg/m2) IV on day -1
Patients receive a PBSC graft infusion from a mismatched unrelated donor on Day 0.
Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.
First 20 patients with a 4-6/8 mismatched unrelated donor will receive an alternate dose of post-transplant cyclophosphamide of 37.5 mg/kg on Days 3 and Day 4 post-transplant.
干预措施: Fludarabine (Drug)
Regimen E (NMA: Fludarabine, Cyclophosphamide, and TBI; PBSCT HCT; Reduced Dose PTCy
Patients receive:
Fludarabine (150mg/m2 total dose) IV on days -6 to -2 Cyclophosphamide (29-50mg/kg) IV on days -6 and -5 TBI (200cGy) on day -1
Patients receive a PBSC graft infusion from a mismatched unrelated donor on Day 0.
Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.
First 20 patients with a 4-6/8 mismatched unrelated donor will receive an alternate dose of post-transplant cyclophosphamide of 37.5 mg/kg on Days 3 and Day 4 post-transplant.
干预措施: Cyclophosphamide (Drug)
Regimen D (RIC: Fludarabine and Melphalan; PBSCT HCT; Reduced Dose PTCy
Patients receive:
Fludarabine (125-150 mg/m2 total dose) IV on days -7 to -3 Melphalan (100-140 mg/m2) IV on day -1
Patients receive a PBSC graft infusion from a mismatched unrelated donor on Day 0.
Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.
First 20 patients with a 4-6/8 mismatched unrelated donor will receive an alternate dose of post-transplant cyclophosphamide of 37.5 mg/kg on Days 3 and Day 4 post-transplant.
干预措施: Tacrolimus (Drug)
Regimen D (RIC: Fludarabine and Melphalan; PBSCT HCT; Reduced Dose PTCy
Patients receive:
Fludarabine (125-150 mg/m2 total dose) IV on days -7 to -3 Melphalan (100-140 mg/m2) IV on day -1
Patients receive a PBSC graft infusion from a mismatched unrelated donor on Day 0.
Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.
First 20 patients with a 4-6/8 mismatched unrelated donor will receive an alternate dose of post-transplant cyclophosphamide of 37.5 mg/kg on Days 3 and Day 4 post-transplant.
干预措施: Mycophenolate Mofetil (Drug)
Regimen D (RIC: Fludarabine and Melphalan; PBSCT HCT; Reduced Dose PTCy
Patients receive:
Fludarabine (125-150 mg/m2 total dose) IV on days -7 to -3 Melphalan (100-140 mg/m2) IV on day -1
Patients receive a PBSC graft infusion from a mismatched unrelated donor on Day 0.
Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.
First 20 patients with a 4-6/8 mismatched unrelated donor will receive an alternate dose of post-transplant cyclophosphamide of 37.5 mg/kg on Days 3 and Day 4 post-transplant.
干预措施: Melphalan (Drug)
Regimen E (NMA: Fludarabine, Cyclophosphamide, and TBI; PBSCT HCT; Reduced Dose PTCy
Patients receive:
Fludarabine (150mg/m2 total dose) IV on days -6 to -2 Cyclophosphamide (29-50mg/kg) IV on days -6 and -5 TBI (200cGy) on day -1
Patients receive a PBSC graft infusion from a mismatched unrelated donor on Day 0.
Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.
First 20 patients with a 4-6/8 mismatched unrelated donor will receive an alternate dose of post-transplant cyclophosphamide of 37.5 mg/kg on Days 3 and Day 4 post-transplant.
干预措施: Post-Transplant Cyclophosphamide (Drug)
Regimen E (NMA: Fludarabine, Cyclophosphamide, and TBI; PBSCT HCT; Reduced Dose PTCy
Patients receive:
Fludarabine (150mg/m2 total dose) IV on days -6 to -2 Cyclophosphamide (29-50mg/kg) IV on days -6 and -5 TBI (200cGy) on day -1
Patients receive a PBSC graft infusion from a mismatched unrelated donor on Day 0.
Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.
First 20 patients with a 4-6/8 mismatched unrelated donor will receive an alternate dose of post-transplant cyclophosphamide of 37.5 mg/kg on Days 3 and Day 4 post-transplant.
干预措施: Fludarabine (Drug)
Regimen E (NMA: Fludarabine, Cyclophosphamide, and TBI; PBSCT HCT; Reduced Dose PTCy
Patients receive:
Fludarabine (150mg/m2 total dose) IV on days -6 to -2 Cyclophosphamide (29-50mg/kg) IV on days -6 and -5 TBI (200cGy) on day -1
Patients receive a PBSC graft infusion from a mismatched unrelated donor on Day 0.
Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.
First 20 patients with a 4-6/8 mismatched unrelated donor will receive an alternate dose of post-transplant cyclophosphamide of 37.5 mg/kg on Days 3 and Day 4 post-transplant.
干预措施: Mycophenolate Mofetil (Drug)
Regimen E (NMA: Fludarabine, Cyclophosphamide, and TBI; PBSCT HCT; Reduced Dose PTCy
Patients receive:
Fludarabine (150mg/m2 total dose) IV on days -6 to -2 Cyclophosphamide (29-50mg/kg) IV on days -6 and -5 TBI (200cGy) on day -1
Patients receive a PBSC graft infusion from a mismatched unrelated donor on Day 0.
Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.
First 20 patients with a 4-6/8 mismatched unrelated donor will receive an alternate dose of post-transplant cyclophosphamide of 37.5 mg/kg on Days 3 and Day 4 post-transplant.
干预措施: Tacrolimus (Drug)
结局指标
主要结局
Infection Free Survival
时间窗: 100 days post-HCT
Survival at 100 days without grades 2-3 infections (per BMT CTN grading criteria)
次要结局
- Cumulative incidence of chronic GvHD(1-year post-HCT)
- Cumulative incidence of grade 2-3 bacterial, fungal, and viral infections(Day 100 and 1-year post-HCT)
- Cumulative incidence of relapse/progression(1-year post-HCT)
- Incidence and Severity of cytokine release syndrome(within 14 days post-HCT)
- Non-relapse mortality(1-year post-HCT)
- Overall Survival(1-year post-HCT)
- Progression-free survival(1-year post-HCT)
- Overall Toxicity(1-year post-HCT)
- Cumulative incidence of neutrophil recovery(Day 28 post-HCT)
- Cumulative incidence of platelet recovery(Day 28 post-HCT)
- Donor T-Cell Chimerism(Day 28, 100 and 365 post-HCT)
- Infection-free survival(1-year post-HCT)
- Graft versus host disease relapse free survival(1-year post-HCT)
- Cumulative incidence of primary and secondary graft failure(Day 28 and 1-year post-HCT)
- Cumulative incidence of acute GvHD(Day 100 and Day 180 post-HCT)
- Cumulative incidence of grades 2-3 BK virus hemorrhagic cystitis(1-year post-HCT)