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

March 16, 2026 updated by: Center for International Blood and Marrow Transplant Research

A Multi-Center, Phase II Trial of HLA-Mismatched Unrelated Donor Hematopoietic Cell Transplantation With Post-Transplantation Cyclophosphamide for Patients With Hematologic Malignancies

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

300

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Duarte, California, United States, 91010
        • City of Hope National Medical Center
      • San Francisco, California, United States, 94143
        • University of California San Francisco
      • Stanford, California, United States, 94305
        • Stanford University
    • Colorado
      • Denver, Colorado, United States, 80218
        • Colorado Blood Cancer Institute
    • Florida
      • Gainesville, Florida, United States, 32610
        • University of Florida Health Shands Hospital
      • Miami, Florida, United States, 33136
        • University of Miami Sylvester Cancer Center
      • Tampa, Florida, United States, 33612
        • H. Lee Moffitt Cancer Center and Research Institute
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Children's Healthcare of Atlanta
      • Atlanta, Georgia, United States, 30322
        • Emory University Medical Center
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University
      • Chicago, Illinois, United States, 60637
        • The University of Chicago
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • University of Maryland Medical Center
      • Baltimore, Maryland, United States, 21231
        • The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
    • Massachusetts
      • Boston, Massachusetts, United States, 02111
        • Tufts Medical Center
      • Boston, Massachusetts, United States, 02215
        • Dana Farber Cancer Institute
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan Medical Center - Mott Children's Hospita
      • Detroit, Michigan, United States, 48201
        • Karmanos Cancer Institute
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic Rochester
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Washington University/Barnes Jewish Hospital
    • New York
      • Buffalo, New York, United States, 14263
        • Roswell Park Comprehensive Cancer Center
      • New York, New York, United States, 10032
        • Columbia University Medical Center
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • University of North Carolina Chapel Hill
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Cincinnati Children's Hospital
      • Columbus, Ohio, United States, 43210
        • Ohio State Medical Center, James Cancer Center
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health and Science University
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Thomas Jefferson University Sidney Kimmel Cancer Center
    • South Carolina
      • Charleston, South Carolina, United States, 29407
        • Medical University of South Carolina
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University Medical Center
      • Nashville, Tennessee, United States, 37203
        • Tristar BMT
      • Nashville, Tennessee, United States, 37203
        • TriStar Medical Group Children's Specialists
    • Texas
      • Austin, Texas, United States, 78704
        • St. David's South Austin Medical Center
      • Houston, Texas, United States, 77030
        • -Baylor College of Medicine - Texas Children's Hospital and Houston Methodist
      • San Antonio, Texas, United States, 37203
        • Texas Transplant Institute
    • Virginia
      • Charlottesville, Virginia, United States, 22903
        • University of Virginia
      • Richmond, Virginia, United States, 23298
        • Virginia Commonwealth University
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • University of Wisconsin Hospital and Clinic
      • Milwaukee, Wisconsin, United States, 53226
        • Froedtert & the Medical College of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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:

    1. 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.
    2. 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.
  7. Cardiac function: Left ventricular ejection fraction > 45% based on most recent echocardiogram or multigated acquisition scan (MUGA) results
  8. Estimated creatinine clearance > 60 mL/min calculated by equation
  9. 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
  10. Liver function acceptable per local institutional guidelines
  11. Karnofsky performance status (KPS) of > 70%
  12. 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

  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:

    1. 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.
    2. 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.
    3. Patients with chronic lymphocytic leukemia (CLL) or other leukemias (including prolymphocytic leukemia) with chemosensitive disease at time of transplantation
    4. Patients with lymphoma with chemosensitive disease at the time of transplantation
  6. Cardiac function: Left ventricular ejection fraction > 45% based on most recent echocardiogram or MUGA results with no clinical evidence of heart failure
  7. Estimated creatinine clearance > 60 mL/min calculated by equation
  8. Pulmonary function: DLCO corrected for hemoglobin > 50% and FEV1 predicted > 50% based on most recent pulmonary function test results
  9. Liver function acceptable per local institutional guidelines
  10. KPS of > 60%
  11. 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

  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:

    1. 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.
    2. 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.
    3. 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.
    4. 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.
    5. Chemotherapy sensitive lymphoma in at least partial remission (PR)
  6. KPS or Lansky performance score ≥ 70%
  7. Cardiac function: Left ventricular ejection fraction of ≥ 50% and shortening fraction of ≥ 27% based on most recent echocardiogram
  8. Glomerular Filtration Rate (GFR) of ≥ 60ml/min/1.73m2 measured by nuclear medicine scan or calculated from a 24 hour urine collection
  9. 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.
  10. Hepatic: Total bilirubin ≤ 2.5 mg/dL and alanine aminotransferase (ALT), aspartate aminotransferase (AST) < 3x the upper limit of normal
  11. 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.
  12. 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:

  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 HSC transplant
  5. Subjects with an autologous HSC transplant within the past 3 months
  6. Females who are breast-feeding or pregnant
  7. Uncontrolled bacterial, viral or fungal infection at the time of the transplant preparative regimen
  8. Concurrent enrollment on other interventional GVHD clinical trial (enrollment on supportive care trials may be allowed after discussion with Principal Investigators)
  9. Subjects who undergo desensitization to reduce anti-donor HLA antibody levels prior to transplant.
  10. 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:

  1. Donor unwilling or unable to donate
  2. 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / 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: Busulfan
Given IV 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®
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.
Radiation: Total-body irradiation
Administered pre-transplant as part of conditioning regimen
Other Names:
  • TBI
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: Busulfan
Given IV 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®
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.
Drug: Melphalan
Given IV pre-transplant as part of conditioning regimen
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®
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.
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®
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 or PO pre-transplant as part of conditioning regimen
Other Names:
  • Busulfex®
Drug: Busulfan
Given IV pre-transplant as part of conditioning regimen
Other Names:
  • Busulfex®
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.
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
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.
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.
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Overall Survival
Time Frame: 1 year post HCT
1 year post HCT

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Event-free survival
Time Frame: 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.
1 year post-HCT
GVHD, relapse free survival
Time Frame: 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.
1 year post-HCT
Modified GVHD, relapse free survival
Time Frame: 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.
1 year post-HCT
Progression-free survival
Time Frame: 1 year post-HCT
1 year post-HCT
Cumulative incidence of nonrelapse mortality
Time Frame: Day +100 and 1 year post-HCT
Day +100 and 1 year post-HCT
Event-Free Survival based on donor HLA match grade and donor age (7/8 versus <7/8)
Time Frame: 1 year post-HCT
1 year post-HCT
Overall Survival based on donor HLA match grade and donor age (7/8 versus <7/8)
Time Frame: 1 year post-HCT
1 year post-HCT
Cumulative incidence of neutrophil recovery
Time Frame: Day +100 post-HCT
Defined as neutrophil count ≥500/mm^3 for 3 consecutive days post-HCT.
Day +100 post-HCT
Kinetics of neutrophil recovery
Time Frame: Day +100 post-HCT
Defined as the evaluation of the time it takes for neutrophil count recovery to occur in the study subjects.
Day +100 post-HCT
Cumulative incidence of platelet recovery
Time Frame: Day +100 post-HCT
Defined as platelet count ≥20,000/mm^3 or ≥50,000/mm^3 with no platelet transfusions within seven days.
Day +100 post-HCT
Kinetics of platelet recovery
Time Frame: Day +100 post-HCT
Defined as the evaluation of the time it takes for platelet count recovery to occur in the study subjects.
Day +100 post-HCT
Cumulative incidence of primary graft failure
Time Frame: Day +28 post-HCT
Day +28 post-HCT
Donor chimerism
Time Frame: Day +100 post-HCT
Strata 2 and 3 only. Percent of donor chimerism via peripheral blood
Day +100 post-HCT
Cumulative incidence of acute GVHD
Time Frame: Day +100 post-HCT
Day +100 post-HCT
Cumulative incidence of chronic GVHD
Time Frame: 1 year post-HCT
1 year post-HCT
Cumulative incidence of BK and cytomegalovirus (CMV) viral infections
Time Frame: Days +100 and +180 post-HCT
Days +100 and +180 post-HCT
Cumulative incidence of relapse/progression
Time Frame: 1 year post-HCT
1 year post-HCT
Incidence of cytokine release syndrome (CRS)
Time Frame: Day +14 post-HCT
Overall incidence of CRS of any grade and grade 3 or 4 CRS post-transplant
Day +14 post-HCT
Cumulative incidence of secondary graft failure
Time Frame: 1 year post-HCT
1 year post-HCT
Overall Toxicity
Time Frame: 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.
1 year post-HCT

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Center for International Blood and Marrow Transplant Research

Collaborators

National Marrow Donor Program

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 30, 2021

Primary Completion (Estimated)

August 1, 2026

Study Completion (Estimated)

December 1, 2026

Study Registration Dates

First Submitted

May 17, 2021

First Submitted That Met QC Criteria

May 26, 2021

First Posted (Actual)

May 27, 2021

Study Record Updates

Last Update Posted (Actual)

March 18, 2026

Last Update Submitted That Met QC Criteria

March 16, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ACCESS

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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