ACCESS: HLA-Mismatched Unrelated Donor Hematopoietic Cell Transplantation With Post-Transplantation Cyclophosphamide

Sponsor
Center for International Blood and Marrow Transplant Research (Other)
Overall Status
Recruiting
CT.gov ID
NCT04904588
Collaborator
National Marrow Donor Program (Other)
180
Enrollment
4
Locations
7
Arms
33
Anticipated Duration (Months)
45
Patients Per Site
1.4
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or DiseaseIntervention/TreatmentPhase
Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
180 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Multi-Center, Phase II Trial of HLA-Mismatched Unrelated Donor Hematopoietic Cell Transplantation With Post-Transplantation Cyclophosphamide for Patients With Hematologic Malignancies
Actual Study Start Date :
Sep 30, 2021
Anticipated Primary Completion Date :
Jul 1, 2024
Anticipated Study Completion Date :
Jul 1, 2024

Arms and Interventions

ArmIntervention/Treatment
Experimental: 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.

Drug: Busulfan
Given IV or PO pre-transplant as part of conditioning regimen
Other Names:
  • Busulfex®
  • Drug: Fludarabine
    Given IV pre-transplant as part of conditioning regimen
    Other Names:
  • Fludara®
  • Procedure: PBSC Hematopoietic Stem Cell Transplantation (HSCT)
    Peripheral blood stem cell graft is infused from a mismatched unrelated donor on Day 0.
    Other Names:
  • PBSC HSCT
  • PBSC HCT
  • PBSC Transplantation
  • Drug: Post-transplant Cyclophosphamide
    Cyclophosphamide (50 mg/kg) is administered on Day +3 and on Day +4 post-transplant as an IV infusion over 1-2 hours.
    Other Names:
  • Cytoxan®
  • Drug: Mesna
    Mesna is given in divided doses IV 30 min pre- and at 3, 6, and 8 hours post-cyclophosphamide.
    Other Names:
  • Mesnex®
  • Drug: Tacrolimus
    Tacrolimus is given at a dose of 0.05 mg/kg PO or an IV dose of 0.03 mg/kg of ideal body weight (IBW) starting on Day +5 post-transplant with taper recommended at 90-100 days post HCT.

    Drug: Mycophenolate Mofetil
    Mycophenolate mofetil (MMF) is given at a dose of 15 mg/kg three times daily IV or PO from Day +5 to Day +35 post-transplant.
    Other Names:
  • MMF
  • Cellcept®
  • Other: Patient-Reported Outcomes
    Survey assessments will be administered to study participants pre- and post-transplant.

    Experimental: 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.

    Drug: Fludarabine
    Given IV pre-transplant as part of conditioning regimen
    Other Names:
  • Fludara®
  • Radiation: Total-body irradiation
    Administered pre-transplant as part of conditioning regimen
    Other Names:
  • TBI
  • Procedure: PBSC Hematopoietic Stem Cell Transplantation (HSCT)
    Peripheral blood stem cell graft is infused from a mismatched unrelated donor on Day 0.
    Other Names:
  • PBSC HSCT
  • PBSC HCT
  • PBSC Transplantation
  • Drug: Post-transplant Cyclophosphamide
    Cyclophosphamide (50 mg/kg) is administered on Day +3 and on Day +4 post-transplant as an IV infusion over 1-2 hours.
    Other Names:
  • Cytoxan®
  • Drug: Mesna
    Mesna is given in divided doses IV 30 min pre- and at 3, 6, and 8 hours post-cyclophosphamide.
    Other Names:
  • Mesnex®
  • Drug: Tacrolimus
    Tacrolimus is given at a dose of 0.05 mg/kg PO or an IV dose of 0.03 mg/kg of ideal body weight (IBW) starting on Day +5 post-transplant with taper recommended at 90-100 days post HCT.

    Drug: Mycophenolate Mofetil
    Mycophenolate mofetil (MMF) is given at a dose of 15 mg/kg three times daily IV or PO from Day +5 to Day +35 post-transplant.
    Other Names:
  • MMF
  • Cellcept®
  • Other: Patient-Reported Outcomes
    Survey assessments will be administered to study participants pre- and post-transplant.

    Experimental: 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.

    Drug: Busulfan
    Given IV or PO pre-transplant as part of conditioning regimen
    Other Names:
  • Busulfex®
  • Drug: Fludarabine
    Given IV pre-transplant as part of conditioning regimen
    Other Names:
  • Fludara®
  • Procedure: PBSC Hematopoietic Stem Cell Transplantation (HSCT)
    Peripheral blood stem cell graft is infused from a mismatched unrelated donor on Day 0.
    Other Names:
  • PBSC HSCT
  • PBSC HCT
  • PBSC Transplantation
  • Drug: Post-transplant Cyclophosphamide
    Cyclophosphamide (50 mg/kg) is administered on Day +3 and on Day +4 post-transplant as an IV infusion over 1-2 hours.
    Other Names:
  • Cytoxan®
  • Drug: Mesna
    Mesna is given in divided doses IV 30 min pre- and at 3, 6, and 8 hours post-cyclophosphamide.
    Other Names:
  • Mesnex®
  • Drug: Tacrolimus
    Tacrolimus is given at a dose of 0.05 mg/kg PO or an IV dose of 0.03 mg/kg of ideal body weight (IBW) starting on Day +5 post-transplant with taper recommended at 90-100 days post HCT.

    Drug: Mycophenolate Mofetil
    Mycophenolate mofetil (MMF) is given at a dose of 15 mg/kg three times daily IV or PO from Day +5 to Day +35 post-transplant.
    Other Names:
  • MMF
  • Cellcept®
  • Other: Patient-Reported Outcomes
    Survey assessments will be administered to study participants pre- and post-transplant.

    Experimental: 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.

    Drug: Fludarabine
    Given IV pre-transplant as part of conditioning regimen
    Other Names:
  • Fludara®
  • Drug: Melphalan
    Given IV pre-transplant as part of conditioning regimen

    Procedure: PBSC Hematopoietic Stem Cell Transplantation (HSCT)
    Peripheral blood stem cell graft is infused from a mismatched unrelated donor on Day 0.
    Other Names:
  • PBSC HSCT
  • PBSC HCT
  • PBSC Transplantation
  • Drug: Post-transplant Cyclophosphamide
    Cyclophosphamide (50 mg/kg) is administered on Day +3 and on Day +4 post-transplant as an IV infusion over 1-2 hours.
    Other Names:
  • Cytoxan®
  • Drug: Mesna
    Mesna is given in divided doses IV 30 min pre- and at 3, 6, and 8 hours post-cyclophosphamide.
    Other Names:
  • Mesnex®
  • Drug: Tacrolimus
    Tacrolimus is given at a dose of 0.05 mg/kg PO or an IV dose of 0.03 mg/kg of ideal body weight (IBW) starting on Day +5 post-transplant with taper recommended at 90-100 days post HCT.

    Drug: Mycophenolate Mofetil
    Mycophenolate mofetil (MMF) is given at a dose of 15 mg/kg three times daily IV or PO from Day +5 to Day +35 post-transplant.
    Other Names:
  • MMF
  • Cellcept®
  • Other: Patient-Reported Outcomes
    Survey assessments will be administered to study participants pre- and post-transplant.

    Experimental: 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.

    Drug: Fludarabine
    Given IV pre-transplant as part of conditioning regimen
    Other Names:
  • Fludara®
  • Radiation: Total-body irradiation
    Administered pre-transplant as part of conditioning regimen
    Other Names:
  • TBI
  • Drug: Cyclophosphamide
    Given IV pre-transplant as part of conditioning regimen
    Other Names:
  • Cytoxan®
  • Procedure: PBSC Hematopoietic Stem Cell Transplantation (HSCT)
    Peripheral blood stem cell graft is infused from a mismatched unrelated donor on Day 0.
    Other Names:
  • PBSC HSCT
  • PBSC HCT
  • PBSC Transplantation
  • Drug: Post-transplant Cyclophosphamide
    Cyclophosphamide (50 mg/kg) is administered on Day +3 and on Day +4 post-transplant as an IV infusion over 1-2 hours.
    Other Names:
  • Cytoxan®
  • Drug: Mesna
    Mesna is given in divided doses IV 30 min pre- and at 3, 6, and 8 hours post-cyclophosphamide.
    Other Names:
  • Mesnex®
  • Drug: Tacrolimus
    Tacrolimus is given at a dose of 0.05 mg/kg PO or an IV dose of 0.03 mg/kg of ideal body weight (IBW) starting on Day +5 post-transplant with taper recommended at 90-100 days post HCT.

    Drug: Mycophenolate Mofetil
    Mycophenolate mofetil (MMF) is given at a dose of 15 mg/kg three times daily IV or PO from Day +5 to Day +35 post-transplant.
    Other Names:
  • MMF
  • Cellcept®
  • Other: Patient-Reported Outcomes
    Survey assessments will be administered to study participants pre- and post-transplant.

    Experimental: 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.

    Drug: Busulfan
    Given IV pre-transplant as part of conditioning regimen
    Other Names:
  • Busulfex®
  • Drug: Cyclophosphamide
    Given IV pre-transplant as part of conditioning regimen
    Other Names:
  • Cytoxan®
  • Procedure: Bone Marrow Hematopoietic Stem Cell Transplantation
    Bone marrow graft is infused from a mismatched unrelated donor on Day 0.
    Other Names:
  • BM HSCT
  • BM HCT
  • Bone Marrow Transplantation
  • Drug: Post-transplant Cyclophosphamide
    Cyclophosphamide (50 mg/kg) is administered on Day +3 and on Day +4 post-transplant as an IV infusion over 1-2 hours.
    Other Names:
  • Cytoxan®
  • Drug: Mesna
    Mesna is given in divided doses IV 30 min pre- and at 3, 6, and 8 hours post-cyclophosphamide.
    Other Names:
  • Mesnex®
  • Drug: Tacrolimus
    Tacrolimus is given at a dose of 0.05 mg/kg PO or an IV dose of 0.03 mg/kg of ideal body weight (IBW) starting on Day +5 post-transplant with taper recommended at 90-100 days post HCT.

    Drug: Mycophenolate Mofetil
    Mycophenolate mofetil (MMF) is given at a dose of 15 mg/kg three times daily IV or PO from Day +5 to Day +35 post-transplant.
    Other Names:
  • MMF
  • Cellcept®
  • Other: Patient-Reported Outcomes
    Survey assessments will be administered to study participants pre- and post-transplant.

    Experimental: 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.

    Radiation: Total-body irradiation
    Administered pre-transplant as part of conditioning regimen
    Other Names:
  • TBI
  • Drug: Cyclophosphamide
    Given IV pre-transplant as part of conditioning regimen
    Other Names:
  • Cytoxan®
  • Procedure: Bone Marrow Hematopoietic Stem Cell Transplantation
    Bone marrow graft is infused from a mismatched unrelated donor on Day 0.
    Other Names:
  • BM HSCT
  • BM HCT
  • Bone Marrow Transplantation
  • Drug: Post-transplant Cyclophosphamide
    Cyclophosphamide (50 mg/kg) is administered on Day +3 and on Day +4 post-transplant as an IV infusion over 1-2 hours.
    Other Names:
  • Cytoxan®
  • Drug: Mesna
    Mesna is given in divided doses IV 30 min pre- and at 3, 6, and 8 hours post-cyclophosphamide.
    Other Names:
  • Mesnex®
  • Drug: Tacrolimus
    Tacrolimus is given at a dose of 0.05 mg/kg PO or an IV dose of 0.03 mg/kg of ideal body weight (IBW) starting on Day +5 post-transplant with taper recommended at 90-100 days post HCT.

    Drug: Mycophenolate Mofetil
    Mycophenolate mofetil (MMF) is given at a dose of 15 mg/kg three times daily IV or PO from Day +5 to Day +35 post-transplant.
    Other Names:
  • MMF
  • Cellcept®
  • Other: Patient-Reported Outcomes
    Survey assessments will be administered to study participants pre- and post-transplant.

    Outcome Measures

    Primary Outcome Measures

    1. Overall Survival [1 year post HCT]

    Secondary Outcome Measures

    1. Event-free survival [1 year post-HCT]

      Defined as graft failure, relapse or progression of underlying disease, death, grade 3-4 acute GVHD, or NIH-severe chronic GVHD.

    2. GVHD, relapse free survival [1 year post-HCT]

      Defined as relapse or progression of underling disease, graft failure, grade III-IV acute GVHD, chronic GVHD requiring systemic immune suppression, or death by any cause.

    3. Modified GVHD, relapse free survival [1 year post-HCT]

      Defined as relapse or progression of underling disease, graft failure, grade III-IV acute GVHD, NIH moderate or severe chronic GVHD, or death by any cause.

    4. Progression-free survival [1 year post-HCT]

    5. Cumulative incidence of nonrelapse mortality [Day +100 and 1 year post-HCT]

    6. Event-Free Survival based on donor HLA match grade and donor age (7/8 versus <7/8) [1 year post-HCT]

    7. Overall Survival based on donor HLA match grade and donor age (7/8 versus <7/8) [1 year post-HCT]

    8. Cumulative incidence of neutrophil recovery [Day +100 post-HCT]

      Defined as neutrophil count ≥500/mm^3 for 3 consecutive days post-HCT.

    9. Kinetics of neutrophil recovery [Day +100 post-HCT]

      Defined as the evaluation of the time it takes for neutrophil count recovery to occur in the study subjects.

    10. Cumulative incidence of platelet recovery [Day +100 post-HCT]

      Defined as platelet count ≥20,000/mm^3 or ≥50,000/mm^3 with no platelet transfusions within seven days.

    11. Kinetics of platelet recovery [Day +100 post-HCT]

      Defined as the evaluation of the time it takes for platelet count recovery to occur in the study subjects.

    12. Cumulative incidence of primary graft failure [Day +28 post-HCT]

    13. Donor chimerism [Day +100 post-HCT]

      Strata 2 and 3 only. Percent of donor chimerism via peripheral blood

    14. Cumulative incidence of acute GVHD [Day +100 post-HCT]

    15. Cumulative incidence of chronic GVHD [1 year post-HCT]

    16. Cumulative incidence of BK and cytomegalovirus (CMV) viral infections [Days +100 and +180 post-HCT]

    17. Cumulative incidence of relapse/progression [1 year post-HCT]

    18. Incidence of cytokine release syndrome (CRS) [Day +14 post-HCT]

      Overall incidence of CRS of any grade and grade 3 or 4 CRS post-transplant

    19. Cumulative incidence of secondary graft failure [1 year post-HCT]

    20. Overall Toxicity [1 year post-HCT]

      To tabulate adverse events (AEs) experienced by recipients, defined as grade 3-5 unexpected and Grade 5 expected AEs, according to CTCAE version 5.0.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    1 Year and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Stratum 1 Recipient Inclusion Criteria:
    1. 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

    2. Planned MAC regimen as defined per protocol

    3. Available partially HLA-MMUD (4/8-7/8 at HLA-A, -B, -C, and -DRB1 is required) with age < 35 years

    4. Product planned for infusion is PBSC

    5. HCT Comorbidity Index (HCT-CI) < 5

    6. One of the following diagnoses:

    7. Acute myelogenous leukemia (AML) 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.

    8. Acute lymphoblastic leukemia (ALL) 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.

    9. 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.

    10. Cardiac function: Left ventricular ejection fraction > 45% based on most recent echocardiogram or multigated acquisition scan (MUGA) results

    11. Estimated creatinine clearance > 60 mL/min calculated by equation

    12. 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 DLCO results

    13. Liver function acceptable per local institutional guidelines

    14. Karnofsky performance status (KPS) of > 70%

    15. Subjects ≥ 18 years of age must have the ability to give informed consent according to applicable regulatory and local institutional requirements.

    Stratum 2 Recipient Inclusion Criteria

    1. Age > 18 years at the time of signing informed consent

    2. Planned NMA/RIC regimen as defined per protocol

    3. Available partially HLA-MMUD (4/8-7/8 at HLA-A, -B, -C, and -DRB1 is required) with age < 35 years

    4. Product planned for infusion is PBSC

    5. One of the following diagnoses:

    6. Patients with acute leukemia or chronic myelogenous 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.

    7. 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.

    8. Patients with relapsed chronic lymphocytic leukemia (CLL) with chemosensitive disease at time of transplantation

    9. Patients with lymphoma with chemosensitive disease at the time of transplantation

    10. Cardiac function: Left ventricular ejection fraction > 45% based on most recent echocardiogram or MUGA results with no clinical evidence of heart failure

    11. Estimated creatinine clearance > 60 mL/min calculated by equation

    12. Pulmonary function: DLCO corrected for hemoglobin > 50% and FEV1 predicted > 50% based on most recent DLCO results

    13. Liver function acceptable per local institutional guidelines

    14. KPS of > 60%

    15. Subjects ≥ 18 years of age must have the ability to give informed consent according to applicable regulatory and local institutional requirements.

    Stratum 3 Recipient Inclusion Criteria

    1. Age > 1 years and < 21 years at the time of signing informed consent

    2. Partially HLA-MMUD (4/8-7/8 at HLA-A, -B, -C, and -DRB1 is required) with age < 35 years

    3. Product planned for infusion is BM

    4. Planned MAC regimen as defined per protocol

    5. One of the following diagnosis:

    6. 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.

    7. 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.

    8. 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.

    9. Other leukemia (mixed-phenotype acute leukemia [MPAL], CML) 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.

    10. Chemotherapy sensitive lymphoma in at least partial remission (PR)

    11. KPS or Lansky performance score ≥ 70%

    12. Cardiac function: Left ventricular ejection fraction of ≥ 50% and shortening fraction of ≥ 27% based on most recent echocardiogram

    13. Glomerular Filtration Rate (GFR) of ≥ 60ml/min/1.73m2 measured by nuclear medicine scan or calculated from a 24 hour urine collection

    14. Pulmonary function: DLCO corrected for hemoglobin, FEV1, 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.

    15. Hepatic: Total bilirubin ≤ 2.5 mg/dL and alanine aminotransferase (ALT), aspartate aminotransferase (AST) < 3x the upper limit of normal

    16. 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.

    17. Subjects ≥ 18 years of age must have the ability to give informed consent according to applicable regulatory and local institutional requirements.

    Donor Inclusion Criteria:
    1. 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 -DRB1)

    2. Donor must be typed at high-resolution for a minimum of HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1

    3. Age > 18 years and < 35 years at the time of signing informed consent

    4. Meet the donor registries' medical suitability requirements for PBSC or BM donation

    5. Must undergo eligibility screening according to current Food and Drug Administration (FDA) requirements. Donors who do not meet one or more of the donor screening requirements may donate under urgent medical need.

    6. Must agree to donate PBSC (or BM for stratum 3)

    7. Must have the ability to give standard (non-study) informed consent according to applicable donor regulatory requirements

    Recipient Exclusion Criteria (Strata 1, 2 and 3):
    1. Suitable HLA-matched related or 8/8 high-resolution matched unrelated donor available

    2. Subject unwilling or unable to give informed consent, or unable to comply with the protocol including required follow-up and testing

    3. Primary myelofibrosis or myelofibrosis secondary to essential thrombocythemia, polycythemia vera, or MDS with grade 4 marrow fibrosis

    4. Subjects with a prior allogeneic transplant or autologous transplant within the past 3 months

    5. Females who are breast-feeding or pregnant

    6. Uncontrolled bacterial, viral or fungal infection at the time of the transplant preparative regimen

    7. Concurrent enrollment on other interventional GVHD clinical trial (enrollment on supportive care trials may be allowed after discussion with Principal Investigators)

    Donor Exclusion Criteria:
    1. Donor unwilling or unable to donate

    2. Recipient positive anti-donor HLA antibodies against a mismatched HLA in the selected donor determined by either:

    3. a positive crossmatch test of any titer (by complement-dependent cytotoxicity or flow cytometric testing) or

    4. the presence of anti-donor HLA antibody to any HLA locus (HLA-A, -B, -C, -DRB1, -DQB1, -DQA1, -DPB1, -DPA1) with mean fluorescence intensity (MFI) >3000 by solid phase immunoassay

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1City of Hope National Medical CenterDuarteCaliforniaUnited States91010
    2Memorial Sloan Kettering Cancer CenterNew YorkNew YorkUnited States10065
    3University of VirginiaCharlottesvilleVirginiaUnited States22903
    4Virginia Commonwealth UniversityRichmondVirginiaUnited States23298

    Sponsors and Collaborators

    • Center for International Blood and Marrow Transplant Research
    • National Marrow Donor Program

    Investigators

    • Principal Investigator: Steven Devine, MD, NMDP/Be The Match

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Center for International Blood and Marrow Transplant Research
    ClinicalTrials.gov Identifier:
    NCT04904588
    Other Study ID Numbers:
    • ACCESS
    First Posted:
    May 27, 2021
    Last Update Posted:
    Oct 20, 2021
    Last Verified:
    Oct 1, 2021

    Study Results

    No Results Posted as of Oct 20, 2021