A Multi-Center, Phase II Trial of HLA-Mismatched Unrelated Donor Hematopoietic Cell Transplantation With Post-Transplantation Cyclophosphamide for Patients With Hematologic Malignancies
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 300
- 试验地点
- 78
- 主要终点
- Overall Survival
研究概览
简要总结
This is a prospective, multi-center, Phase II study of hematopoietic cell transplantation (HCT) using human leukocyte antigen (HLA)-mismatched unrelated donors (MMUD) for peripheral blood stem cell transplant in adults and bone marrow stem cell transplant in children. Post-transplant cyclophosphamide (PTCy), tacrolimus and mycophenolate mofetil (MMF) will be used for for graft versus host disease (GVHD) prophylaxis. This trial will study how well this treatment works in patients with hematologic malignancies.
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
- 1 Year 至 —（Child, 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
- •Planned MAC regimen as defined per protocol
- •Available partially HLA-MMUD (4/8-7/8 at HLA-A, -B, -C, and -DRB1 is required) with age < 35 years
- •Product planned for infusion is PBSC
- •HCT Comorbidity Index (HCT-CI) < 5
- •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 myelodysplastic syndrome (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 multigated acquisition scan (MUGA) results
- •Estimated creatinine clearance > 60 mL/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 results
- •Liver function acceptable per local institutional guidelines
- •Karnofsky performance status (KPS) of > 70%
- •Subjects ≥ 18 years of age or legally authorized representative must have the ability to give informed consent according to applicable regulatory and local institutional requirements.
- •Stratum 2 Recipient Inclusion Criteria
- •Age > 18 years at the time of signing informed consent
- •Planned NMA/RIC regimen as defined per protocol
- •Available partially HLA-MMUD (4/8-7/8 at HLA-A, -B, -C, and -DRB1 is required) with age < 35 years
- •Product planned for infusion is PBSC
- •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
- •Patients with lymphoma with chemosensitive disease at the time of transplantation
- •Cardiac function: Left ventricular ejection fraction > 45% based on most recent echocardiogram or MUGA results with no clinical evidence of heart failure
- •Estimated creatinine clearance > 60 mL/min calculated by equation
- •Pulmonary function: DLCO corrected for hemoglobin > 50% and FEV1 predicted > 50% based on most recent pulmonary function test results
- •Liver function acceptable per local institutional guidelines
- •KPS of > 60%
- •Subjects ≥ 18 years of age or legally authorized representative must have the ability to give informed consent according to applicable regulatory and local institutional requirements.
- •Stratum 3 Recipient Inclusion Criteria
- •Age > 1 years and < 21 years at the time of signing informed consent
- •Partially HLA-MMUD (4/8-7/8 at HLA-A, -B, -C, and -DRB1 is required) with age < 35 years
- •Product planned for infusion is BM
- •Planned MAC regimen as defined per protocol
- •One of the following diagnosis:
- •AML in 1st remission or beyond with ≤ 5% marrow blasts, no circulating blasts or evidence of extra-medullary disease. Pre-transplant MRD testing will be performed as per standard of practice at the treating institution. Patients with any MRD status are eligible and should be enrolled at the discretion of provider. Documentation of bone marrow assessment will be accepted within 45 days prior to the anticipated start of conditioning.
- •Patients MDS with no circulating blasts and less than 10% blasts in the bone marrow. Documentation of bone marrow assessment will be accepted within 45 days prior to the anticipated start of conditioning.
- •ALL in 1st remission or beyond with ≤ 5% marrow blasts, no circulating blasts, or evidence of extra-medullary disease. Pre-transplant MRD testing will be performed as standard practice at the treating institution with the goal of achieving MRD of <0.01%. Patients with any MRD status are eligible and should be enrolled at the discretion of provider. Documentation of bone marrow assessment will be accepted within 45 days prior to the anticipated start of conditioning.
- •Other leukemia (mixed-phenotype acute leukemia [MPAL], CML, or other leukemia) in morphologic remission with ≤ 5% marrow blasts and no circulating blasts or evidence of extramedullary disease. Documentation of bone marrow assessment will be accepted within 45 days prior to the anticipated start of conditioning.
- •Chemotherapy sensitive lymphoma in at least partial remission (PR)
- •KPS or Lansky performance score ≥ 70%
- •Cardiac function: Left ventricular ejection fraction of ≥ 50% and shortening fraction of ≥ 27% based on most recent echocardiogram
- •Glomerular Filtration Rate (GFR) of ≥ 60ml/min/1.73m2 measured by nuclear medicine scan or calculated from a 24 hour urine collection
- •Pulmonary function: DLCO corrected for hemoglobin, FEV1, and Forced Vital Capacity (FVC) of ≥50% if able to perform pulmonary function tests. If unable to perform pulmonary function tests, must have a resting pulse oximetry of >92% without supplemental oxygen.
- •Hepatic: Total bilirubin ≤ 2.5 mg/dL and alanine aminotransferase (ALT), aspartate aminotransferase (AST) < 3x the upper limit of normal
- •Legal guardian permission must be obtained for subjects < 18 years of age. Pediatric subjects will be included in age appropriate discussion in order to obtain assent.
- •Subjects ≥ 18 years of age or legally authorized representative must have the ability to give informed consent according to applicable regulatory and local institutional requirements.
- •Donor Inclusion Criteria:
- 另有 7 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
- •Primary myelofibrosis or myelofibrosis secondary to essential thrombocythemia, polycythemia vera, or MDS with grade 4 marrow fibrosis
- •Subjects with a prior allogeneic HSC transplant
- •Subjects with an autologous HSC 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 other interventional GVHD clinical trial (enrollment on supportive care trials may be allowed after discussion with Principal Investigators)
- •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 with undetectable viral load within 6 months are eligible for this trial.
- •Donor Exclusion Criteria:
- •Donor unwilling or unable to donate
- •Recipient positive anti-donor 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)
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.
干预措施: PBSC Hematopoietic Stem Cell Transplantation (HSCT) (Procedure)
Regimen A (MAC: busulfan and fludarabine, PBSC HCT)
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.
干预措施: Busulfan (Drug)
Regimen A (MAC: busulfan and fludarabine, PBSC HCT)
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.
干预措施: Fludarabine (Drug)
Regimen B (MAC: Fludarabine and TBI; PBSC HCT)
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 PBSC graft infusion from a mismatched unrelated donor on Day 0.
干预措施: Total-body irradiation (Radiation)
Regimen A (MAC: busulfan and fludarabine, PBSC HCT)
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.
干预措施: Post-transplant Cyclophosphamide (Drug)
Regimen A (MAC: busulfan and fludarabine, PBSC HCT)
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.
干预措施: Mesna (Drug)
Regimen A (MAC: busulfan and fludarabine, PBSC HCT)
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.
干预措施: Tacrolimus (Drug)
Regimen A (MAC: busulfan and fludarabine, PBSC HCT)
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.
干预措施: Mycophenolate Mofetil (Drug)
Regimen A (MAC: busulfan and fludarabine, PBSC HCT)
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.
干预措施: Patient-Reported Outcomes (Other)
Regimen B (MAC: Fludarabine and TBI; PBSC HCT)
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 PBSC graft infusion from a mismatched unrelated donor on Day 0.
干预措施: Fludarabine (Drug)
Regimen B (MAC: Fludarabine and TBI; PBSC HCT)
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 PBSC graft infusion from a mismatched unrelated donor on Day 0.
干预措施: PBSC Hematopoietic Stem Cell Transplantation (HSCT) (Procedure)
Regimen B (MAC: Fludarabine and TBI; PBSC HCT)
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 PBSC graft infusion from a mismatched unrelated donor on Day 0.
干预措施: Post-transplant Cyclophosphamide (Drug)
Regimen B (MAC: Fludarabine and TBI; PBSC HCT)
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 PBSC graft infusion from a mismatched unrelated donor on Day 0.
干预措施: Mesna (Drug)
Regimen B (MAC: Fludarabine and TBI; PBSC HCT)
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 PBSC graft infusion from a mismatched unrelated donor on Day 0.
干预措施: Tacrolimus (Drug)
Regimen B (MAC: Fludarabine and TBI; PBSC HCT)
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 PBSC graft infusion from a mismatched unrelated donor on Day 0.
干预措施: Mycophenolate Mofetil (Drug)
Regimen B (MAC: Fludarabine and TBI; PBSC HCT)
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 PBSC graft infusion from a mismatched unrelated donor on Day 0.
干预措施: Patient-Reported Outcomes (Other)
Regimen C (RIC: Fludarabine and Busulfan; PBSC HCT)
Patients receive:
- Fludarabine (120-180 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 PBSC graft infusion from a mismatched unrelated donor on Day 0.
干预措施: Busulfan (Drug)
Regimen C (RIC: Fludarabine and Busulfan; PBSC HCT)
Patients receive:
- Fludarabine (120-180 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 PBSC graft infusion from a mismatched unrelated donor on Day 0.
干预措施: Fludarabine (Drug)
Regimen C (RIC: Fludarabine and Busulfan; PBSC HCT)
Patients receive:
- Fludarabine (120-180 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 PBSC graft infusion from a mismatched unrelated donor on Day 0.
干预措施: PBSC Hematopoietic Stem Cell Transplantation (HSCT) (Procedure)
Regimen C (RIC: Fludarabine and Busulfan; PBSC HCT)
Patients receive:
- Fludarabine (120-180 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 PBSC graft infusion from a mismatched unrelated donor on Day 0.
干预措施: Post-transplant Cyclophosphamide (Drug)
Regimen C (RIC: Fludarabine and Busulfan; PBSC HCT)
Patients receive:
- Fludarabine (120-180 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 PBSC graft infusion from a mismatched unrelated donor on Day 0.
干预措施: Mesna (Drug)
Regimen C (RIC: Fludarabine and Busulfan; PBSC HCT)
Patients receive:
- Fludarabine (120-180 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 PBSC graft infusion from a mismatched unrelated donor on Day 0.
干预措施: Tacrolimus (Drug)
Regimen C (RIC: Fludarabine and Busulfan; PBSC HCT)
Patients receive:
- Fludarabine (120-180 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 PBSC graft infusion from a mismatched unrelated donor on Day 0.
干预措施: Mycophenolate Mofetil (Drug)
Regimen C (RIC: Fludarabine and Busulfan; PBSC HCT)
Patients receive:
- Fludarabine (120-180 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 PBSC graft infusion from a mismatched unrelated donor on Day 0.
干预措施: Patient-Reported Outcomes (Other)
Regimen D (RIC: Fludarabine and Melphalan; PBSC HCT)
Patients receive:
- Fludarabine (120-180 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.
干预措施: Fludarabine (Drug)
Regimen D (RIC: Fludarabine and Melphalan; PBSC HCT)
Patients receive:
- Fludarabine (120-180 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.
干预措施: Melphalan (Drug)
Regimen D (RIC: Fludarabine and Melphalan; PBSC HCT)
Patients receive:
- Fludarabine (120-180 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.
干预措施: PBSC Hematopoietic Stem Cell Transplantation (HSCT) (Procedure)
Regimen D (RIC: Fludarabine and Melphalan; PBSC HCT)
Patients receive:
- Fludarabine (120-180 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.
干预措施: Post-transplant Cyclophosphamide (Drug)
Regimen D (RIC: Fludarabine and Melphalan; PBSC HCT)
Patients receive:
- Fludarabine (120-180 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.
干预措施: Mesna (Drug)
Regimen D (RIC: Fludarabine and Melphalan; PBSC HCT)
Patients receive:
- Fludarabine (120-180 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.
干预措施: Tacrolimus (Drug)
Regimen D (RIC: Fludarabine and Melphalan; PBSC HCT)
Patients receive:
- Fludarabine (120-180 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.
干预措施: Mycophenolate Mofetil (Drug)
Regimen E (NMA: Fludarabine, Cyclophosphamide, TBI; PBSC HCT)
Patients receive:
- Fludarabine (150 mg/m2 total dose) IV on days -6 to -2
- Cyclophosphamide (29-50 mg/kg) IV on days -6 and -5
- TBI (200 cGy) on day -1
Patients receive a PBSC graft infusion from a mismatched unrelated donor on Day 0.
干预措施: Tacrolimus (Drug)
Regimen D (RIC: Fludarabine and Melphalan; PBSC HCT)
Patients receive:
- Fludarabine (120-180 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.
干预措施: Patient-Reported Outcomes (Other)
Regimen E (NMA: Fludarabine, Cyclophosphamide, TBI; PBSC HCT)
Patients receive:
- Fludarabine (150 mg/m2 total dose) IV on days -6 to -2
- Cyclophosphamide (29-50 mg/kg) IV on days -6 and -5
- TBI (200 cGy) on day -1
Patients receive a PBSC graft infusion from a mismatched unrelated donor on Day 0.
干预措施: Fludarabine (Drug)
Regimen E (NMA: Fludarabine, Cyclophosphamide, TBI; PBSC HCT)
Patients receive:
- Fludarabine (150 mg/m2 total dose) IV on days -6 to -2
- Cyclophosphamide (29-50 mg/kg) IV on days -6 and -5
- TBI (200 cGy) on day -1
Patients receive a PBSC graft infusion from a mismatched unrelated donor on Day 0.
干预措施: Total-body irradiation (Radiation)
Regimen E (NMA: Fludarabine, Cyclophosphamide, TBI; PBSC HCT)
Patients receive:
- Fludarabine (150 mg/m2 total dose) IV on days -6 to -2
- Cyclophosphamide (29-50 mg/kg) IV on days -6 and -5
- TBI (200 cGy) on day -1
Patients receive a PBSC graft infusion from a mismatched unrelated donor on Day 0.
干预措施: Cyclophosphamide (Drug)
Regimen E (NMA: Fludarabine, Cyclophosphamide, TBI; PBSC HCT)
Patients receive:
- Fludarabine (150 mg/m2 total dose) IV on days -6 to -2
- Cyclophosphamide (29-50 mg/kg) IV on days -6 and -5
- TBI (200 cGy) on day -1
Patients receive a PBSC graft infusion from a mismatched unrelated donor on Day 0.
干预措施: PBSC Hematopoietic Stem Cell Transplantation (HSCT) (Procedure)
Regimen E (NMA: Fludarabine, Cyclophosphamide, TBI; PBSC HCT)
Patients receive:
- Fludarabine (150 mg/m2 total dose) IV on days -6 to -2
- Cyclophosphamide (29-50 mg/kg) IV on days -6 and -5
- TBI (200 cGy) on day -1
Patients receive a PBSC graft infusion from a mismatched unrelated donor on Day 0.
干预措施: Post-transplant Cyclophosphamide (Drug)
Regimen E (NMA: Fludarabine, Cyclophosphamide, TBI; PBSC HCT)
Patients receive:
- Fludarabine (150 mg/m2 total dose) IV on days -6 to -2
- Cyclophosphamide (29-50 mg/kg) IV on days -6 and -5
- TBI (200 cGy) on day -1
Patients receive a PBSC graft infusion from a mismatched unrelated donor on Day 0.
干预措施: Mesna (Drug)
Regimen E (NMA: Fludarabine, Cyclophosphamide, TBI; PBSC HCT)
Patients receive:
- Fludarabine (150 mg/m2 total dose) IV on days -6 to -2
- Cyclophosphamide (29-50 mg/kg) IV on days -6 and -5
- TBI (200 cGy) on day -1
Patients receive a PBSC graft infusion from a mismatched unrelated donor on Day 0.
干预措施: Mycophenolate Mofetil (Drug)
Regimen E (NMA: Fludarabine, Cyclophosphamide, TBI; PBSC HCT)
Patients receive:
- Fludarabine (150 mg/m2 total dose) IV on days -6 to -2
- Cyclophosphamide (29-50 mg/kg) IV on days -6 and -5
- TBI (200 cGy) on day -1
Patients receive a PBSC graft infusion from a mismatched unrelated donor on Day 0.
干预措施: Patient-Reported Outcomes (Other)
Regimen F (MAC: Busulfan and Cyclophosphamide; BM HCT)
Patients receive:
- Busulfan (dosed by age and weight per institutional standards to target goal pharmacokinetic (PK) in range noted in protocol.) on days -6 to -3
- Cyclophosphamide (100 mg/kg total dose) IV on days -2 and -1
Patients receive a bone marrow (BM) graft infusion from a mismatched unrelated donor on Day 0.
干预措施: Busulfan (Drug)
Regimen F (MAC: Busulfan and Cyclophosphamide; BM HCT)
Patients receive:
- Busulfan (dosed by age and weight per institutional standards to target goal pharmacokinetic (PK) in range noted in protocol.) on days -6 to -3
- Cyclophosphamide (100 mg/kg total dose) IV on days -2 and -1
Patients receive a bone marrow (BM) graft infusion from a mismatched unrelated donor on Day 0.
干预措施: Cyclophosphamide (Drug)
Regimen F (MAC: Busulfan and Cyclophosphamide; BM HCT)
Patients receive:
- Busulfan (dosed by age and weight per institutional standards to target goal pharmacokinetic (PK) in range noted in protocol.) on days -6 to -3
- Cyclophosphamide (100 mg/kg total dose) IV on days -2 and -1
Patients receive a bone marrow (BM) graft infusion from a mismatched unrelated donor on Day 0.
干预措施: Bone Marrow Hematopoietic Stem Cell Transplantation (Procedure)
Regimen F (MAC: Busulfan and Cyclophosphamide; BM HCT)
Patients receive:
- Busulfan (dosed by age and weight per institutional standards to target goal pharmacokinetic (PK) in range noted in protocol.) on days -6 to -3
- Cyclophosphamide (100 mg/kg total dose) IV on days -2 and -1
Patients receive a bone marrow (BM) graft infusion from a mismatched unrelated donor on Day 0.
干预措施: Post-transplant Cyclophosphamide (Drug)
Regimen F (MAC: Busulfan and Cyclophosphamide; BM HCT)
Patients receive:
- Busulfan (dosed by age and weight per institutional standards to target goal pharmacokinetic (PK) in range noted in protocol.) on days -6 to -3
- Cyclophosphamide (100 mg/kg total dose) IV on days -2 and -1
Patients receive a bone marrow (BM) graft infusion from a mismatched unrelated donor on Day 0.
干预措施: Mesna (Drug)
Regimen F (MAC: Busulfan and Cyclophosphamide; BM HCT)
Patients receive:
- Busulfan (dosed by age and weight per institutional standards to target goal pharmacokinetic (PK) in range noted in protocol.) on days -6 to -3
- Cyclophosphamide (100 mg/kg total dose) IV on days -2 and -1
Patients receive a bone marrow (BM) graft infusion from a mismatched unrelated donor on Day 0.
干预措施: Tacrolimus (Drug)
Regimen F (MAC: Busulfan and Cyclophosphamide; BM HCT)
Patients receive:
- Busulfan (dosed by age and weight per institutional standards to target goal pharmacokinetic (PK) in range noted in protocol.) on days -6 to -3
- Cyclophosphamide (100 mg/kg total dose) IV on days -2 and -1
Patients receive a bone marrow (BM) graft infusion from a mismatched unrelated donor on Day 0.
干预措施: Mycophenolate Mofetil (Drug)
Regimen F (MAC: Busulfan and Cyclophosphamide; BM HCT)
Patients receive:
- Busulfan (dosed by age and weight per institutional standards to target goal pharmacokinetic (PK) in range noted in protocol.) on days -6 to -3
- Cyclophosphamide (100 mg/kg total dose) IV on days -2 and -1
Patients receive a bone marrow (BM) graft infusion from a mismatched unrelated donor on Day 0.
干预措施: Patient-Reported Outcomes (Other)
Regimen G (MAC: Cyclophosphamide and TBI; BM HCT)
Patients receive:
- Cyclophosphamide (100 mg/kg total dose) IV on days -5 and -4
- TBI (1200 cGy total dose) on days -3, -2 and -1
Patients receive a BM graft infusion from a mismatched unrelated donor on Day 0.
干预措施: Total-body irradiation (Radiation)
Regimen G (MAC: Cyclophosphamide and TBI; BM HCT)
Patients receive:
- Cyclophosphamide (100 mg/kg total dose) IV on days -5 and -4
- TBI (1200 cGy total dose) on days -3, -2 and -1
Patients receive a BM graft infusion from a mismatched unrelated donor on Day 0.
干预措施: Cyclophosphamide (Drug)
Regimen G (MAC: Cyclophosphamide and TBI; BM HCT)
Patients receive:
- Cyclophosphamide (100 mg/kg total dose) IV on days -5 and -4
- TBI (1200 cGy total dose) on days -3, -2 and -1
Patients receive a BM graft infusion from a mismatched unrelated donor on Day 0.
干预措施: Bone Marrow Hematopoietic Stem Cell Transplantation (Procedure)
Regimen G (MAC: Cyclophosphamide and TBI; BM HCT)
Patients receive:
- Cyclophosphamide (100 mg/kg total dose) IV on days -5 and -4
- TBI (1200 cGy total dose) on days -3, -2 and -1
Patients receive a BM graft infusion from a mismatched unrelated donor on Day 0.
干预措施: Post-transplant Cyclophosphamide (Drug)
Regimen G (MAC: Cyclophosphamide and TBI; BM HCT)
Patients receive:
- Cyclophosphamide (100 mg/kg total dose) IV on days -5 and -4
- TBI (1200 cGy total dose) on days -3, -2 and -1
Patients receive a BM graft infusion from a mismatched unrelated donor on Day 0.
干预措施: Mesna (Drug)
Regimen G (MAC: Cyclophosphamide and TBI; BM HCT)
Patients receive:
- Cyclophosphamide (100 mg/kg total dose) IV on days -5 and -4
- TBI (1200 cGy total dose) on days -3, -2 and -1
Patients receive a BM graft infusion from a mismatched unrelated donor on Day 0.
干预措施: Tacrolimus (Drug)
Regimen G (MAC: Cyclophosphamide and TBI; BM HCT)
Patients receive:
- Cyclophosphamide (100 mg/kg total dose) IV on days -5 and -4
- TBI (1200 cGy total dose) on days -3, -2 and -1
Patients receive a BM graft infusion from a mismatched unrelated donor on Day 0.
干预措施: Mycophenolate Mofetil (Drug)
Regimen G (MAC: Cyclophosphamide and TBI; BM HCT)
Patients receive:
- Cyclophosphamide (100 mg/kg total dose) IV on days -5 and -4
- TBI (1200 cGy total dose) on days -3, -2 and -1
Patients receive a BM graft infusion from a mismatched unrelated donor on Day 0.
干预措施: Patient-Reported Outcomes (Other)
结局指标
主要结局
Overall Survival
时间窗: 1 year post HCT
次要结局
- Cumulative incidence of relapse/progression(1 year post-HCT)
- GVHD, relapse free survival(1 year post-HCT)
- Modified GVHD, relapse free survival(1 year post-HCT)
- Event-Free Survival based on donor HLA match grade and donor age (7/8 versus <7/8)(1 year post-HCT)
- Kinetics of platelet recovery(Day +100 post-HCT)
- Overall Toxicity(1 year post-HCT)
- Event-free survival(1 year post-HCT)
- Overall Survival based on donor HLA match grade and donor age (7/8 versus <7/8)(1 year post-HCT)
- Cumulative incidence of neutrophil recovery(Day +100 post-HCT)
- Kinetics of neutrophil recovery(Day +100 post-HCT)
- Cumulative incidence of platelet recovery(Day +100 post-HCT)
- Cumulative incidence of primary graft failure(Day +28 post-HCT)
- Donor chimerism(Day +100 post-HCT)
- Cumulative incidence of nonrelapse mortality(Day +100 and 1 year post-HCT)
- Cumulative incidence of acute GVHD(Day +100 post-HCT)
- Cumulative incidence of chronic GVHD(1 year post-HCT)
- Incidence of cytokine release syndrome (CRS)(Day +14 post-HCT)
- Progression-free survival(1 year post-HCT)
- Cumulative incidence of BK and cytomegalovirus (CMV) viral infections(Days +100 and +180 post-HCT)
- Cumulative incidence of secondary graft failure(1 year post-HCT)