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

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ClinicalTrials.gov Identifier: NCT04904588
Recruitment Status : Recruiting
First Posted : May 27, 2021
Last Update Posted : October 20, 2021
Sponsor:
Collaborator:
National Marrow Donor Program
Information provided by (Responsible Party):
Center for International Blood and Marrow Transplant Research

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 disease Intervention/treatment Phase
Acute Lymphoblastic Leukemia Acute Myelogenous Leukemia Mixed Phenotype Acute Leukemia Acute Leukemia Myelodysplastic Syndromes Chronic Myelogenous Leukemia Chronic Lymphocytic Leukemia Lymphoma Drug: Busulfan Drug: Fludarabine Radiation: Total-body irradiation Drug: Cyclophosphamide Drug: Melphalan Procedure: PBSC Hematopoietic Stem Cell Transplantation (HSCT) Procedure: Bone Marrow Hematopoietic Stem Cell Transplantation Drug: Post-transplant Cyclophosphamide Drug: Mesna Drug: Tacrolimus Drug: Mycophenolate Mofetil Other: Patient-Reported Outcomes Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated 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 : September 30, 2021
Estimated Primary Completion Date : July 2024
Estimated Study Completion Date : July 2024


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 Name: Busulfex®

Drug: Fludarabine
Given IV pre-transplant as part of conditioning regimen
Other Name: 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 Name: Cytoxan®

Drug: Mesna
Mesna is given in divided doses IV 30 min pre- and at 3, 6, and 8 hours post-cyclophosphamide.
Other Name: 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 Name: Fludara®

Radiation: Total-body irradiation
Administered pre-transplant as part of conditioning regimen
Other Name: 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 Name: Cytoxan®

Drug: Mesna
Mesna is given in divided doses IV 30 min pre- and at 3, 6, and 8 hours post-cyclophosphamide.
Other Name: 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 Name: Busulfex®

Drug: Fludarabine
Given IV pre-transplant as part of conditioning regimen
Other Name: 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 Name: Cytoxan®

Drug: Mesna
Mesna is given in divided doses IV 30 min pre- and at 3, 6, and 8 hours post-cyclophosphamide.
Other Name: 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 Name: 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 Name: Cytoxan®

Drug: Mesna
Mesna is given in divided doses IV 30 min pre- and at 3, 6, and 8 hours post-cyclophosphamide.
Other Name: 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 Name: Fludara®

Radiation: Total-body irradiation
Administered pre-transplant as part of conditioning regimen
Other Name: TBI

Drug: Cyclophosphamide
Given IV pre-transplant as part of conditioning regimen
Other Name: 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 Name: Cytoxan®

Drug: Mesna
Mesna is given in divided doses IV 30 min pre- and at 3, 6, and 8 hours post-cyclophosphamide.
Other Name: 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 Name: Busulfex®

Drug: Cyclophosphamide
Given IV pre-transplant as part of conditioning regimen
Other Name: 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 Name: Cytoxan®

Drug: Mesna
Mesna is given in divided doses IV 30 min pre- and at 3, 6, and 8 hours post-cyclophosphamide.
Other Name: 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 Name: TBI

Drug: Cyclophosphamide
Given IV pre-transplant as part of conditioning regimen
Other Name: 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 Name: Cytoxan®

Drug: Mesna
Mesna is given in divided doses IV 30 min pre- and at 3, 6, and 8 hours post-cyclophosphamide.
Other Name: 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.




Primary Outcome Measures :
  1. Overall Survival [ Time Frame: 1 year post HCT ]

Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. Progression-free survival [ Time Frame: 1 year post-HCT ]
  5. Cumulative incidence of nonrelapse mortality [ Time Frame: 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) [ Time Frame: 1 year post-HCT ]
  7. Overall Survival based on donor HLA match grade and donor age (7/8 versus <7/8) [ Time Frame: 1 year post-HCT ]
  8. Cumulative incidence of neutrophil recovery [ Time Frame: Day +100 post-HCT ]
    Defined as neutrophil count ≥500/mm^3 for 3 consecutive days post-HCT.

  9. 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.

  10. 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.

  11. 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.

  12. Cumulative incidence of primary graft failure [ Time Frame: Day +28 post-HCT ]
  13. Donor chimerism [ Time Frame: Day +100 post-HCT ]
    Strata 2 and 3 only. Percent of donor chimerism via peripheral blood

  14. Cumulative incidence of acute GVHD [ Time Frame: Day +100 post-HCT ]
  15. Cumulative incidence of chronic GVHD [ Time Frame: 1 year post-HCT ]
  16. Cumulative incidence of BK and cytomegalovirus (CMV) viral infections [ Time Frame: Days +100 and +180 post-HCT ]
  17. Cumulative incidence of relapse/progression [ Time Frame: 1 year post-HCT ]
  18. 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

  19. Cumulative incidence of secondary graft failure [ Time Frame: 1 year post-HCT ]
  20. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   1 Year and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 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.
    2. 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.
    3. 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 DLCO results
  10. Liver function acceptable per local institutional guidelines
  11. Karnofsky performance status (KPS) of > 70%
  12. 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:

    1. 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.
    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 relapsed chronic lymphocytic leukemia (CLL) 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 DLCO results
  9. Liver function acceptable per local institutional guidelines
  10. KPS of > 60%
  11. 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:

    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) 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, 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 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:

    1. a positive crossmatch test of any titer (by complement-dependent cytotoxicity or flow cytometric testing) or
    2. 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04904588


Contacts
Layout table for location contacts
Contact: Janelle Olson, PhD 763-406-8147 jolson@nmdp.org
Contact: Erin Leckrone 763-406-5124 eleckron@nmdp.org

Locations
Layout table for location information
United States, California
City of Hope National Medical Center Recruiting
Duarte, California, United States, 91010
Contact: Monzr Al Malki, MD         
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Brian Shaffer, MD         
United States, Virginia
University of Virginia Recruiting
Charlottesville, Virginia, United States, 22903
Contact: Karen Ballen, MD         
Virginia Commonwealth University Recruiting
Richmond, Virginia, United States, 23298
Contact: John McCarty, MD         
Sponsors and Collaborators
Center for International Blood and Marrow Transplant Research
National Marrow Donor Program
Investigators
Layout table for investigator information
Principal Investigator: Steven Devine, MD NMDP/Be The Match
Layout table for additonal information
Responsible Party: Center for International Blood and Marrow Transplant Research
ClinicalTrials.gov Identifier: NCT04904588    
Other Study ID Numbers: ACCESS
First Posted: May 27, 2021    Key Record Dates
Last Update Posted: October 20, 2021
Last Verified: October 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Center for International Blood and Marrow Transplant Research:
Lymphoma
Leukemia
Hematologic Diseases
Myelodysplastic Syndromes
Preleukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Myeloid, Acute
Leukemia, Biphenotypic, Acute
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Bone Marrow Diseases
Precancerous Conditions
Leukemia, Lymphoid
Leukemia, B-Cell
Leukemia, Myeloid
Cyclophosphamide
Mesna
Tacrolimus
Busulfan
Fludarabine
Total Body Irradiation
Melphalan
Mycophenolate mofetil
Immunosuppressive Agents
Immunologic Factors
Additional relevant MeSH terms:
Layout table for MeSH terms
Lymphoma
Leukemia
Preleukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Acute Disease
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Pathologic Processes
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Leukemia, B-Cell
Myeloproliferative Disorders
Disease Attributes
Mycophenolic Acid
Cyclophosphamide
Melphalan
Busulfan
Fludarabine
Tacrolimus