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

What's the purpose of this trial?

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.

This trial is currently open and accepting patients.


What will happen during the trial?

You may be able to join this trial if you:

The following criteria is a partial list of reasons why patients may be eligible to participate in this clinical trial. Further evaluation with a medical professional is required.

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 transplant
  5. Subjects with an autologous 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.

Additional Trial Information

Phase 2

Enrollment: 200 patients (estimated)

View More

Trial Locations

All Trial Locations

View all clinical trial locations sorted by state.

California

City of Hope Comprehensive Cancer Center Beckman Research Institute

Duarte, CA

Open and Accepting

Stanford University Cancer Institute (Palo Alto)

Stanford, CA

Open and Accepting

Colorado

Florida

Shands Hospital University of Florida Health

Gainesville, FL

Open and Accepting

Moffitt Cancer Center Magnolia Campus

Tampa, FL

Open and Accepting

Georgia

Children's Healthcare of Atlanta Egleston Hospital

Atlanta, GA

Open and Accepting

Emory University Winship Cancer Institute - Midtown

Atlanta, GA

Open and Accepting

Illinois

University of Chicago Medicine Comprehensive Cancer Center

Chicago, IL

Open and Accepting

Maryland

Sidney Kimmel Comprehensive Cancer Center Johns Hopkins Medicine

Baltimore, MD

Open and Accepting

Massachusetts

Tufts Medical Center Cancer Center

Boston, MA

Open and Accepting

Dana-Farber Cancer Institute

Boston, MA

Open and Accepting

Michigan

Barbara Ann Karmanos Cancer Institute Wayne State University

Detroit, MI

Open and Accepting

Minnesota

Mayo Clinic (Rochester)

Rochester, MN

Open and Accepting

Missouri

Siteman Cancer Center at Barnes-Jewish West County Hospital

Creve Coeur, MO

Open and Accepting

New York

Roswell Park Cancer Institute

Buffalo, NY

Open and Accepting

North Carolina

UNC Lineberger Comprehensive Cancer Center University of North Carolina

Chapel Hill, NC

Open and Accepting

Ohio

Cincinnati Children's Hospital Medical Center

Cincinnati, OH

Open and Accepting

Oregon

Oregon Health and Science University OHSU Knight Cancer Institute

Portland, OR

Open and Accepting

Pennsylvania

Thomas Jefferson University Hospital

Philadelphia, PA

Open and Accepting

South Carolina

Medical University of South Carolina

Charleston, SC

Open and Accepting

Tennessee

Vanderbilt-Ingram Cancer Center Henry-Joyce Cancer Clinic

Nashville, TN

Open and Accepting

Texas

St. David's South Austin Medical Center

Austin, TX

Open and Accepting

Baylor College of Medicine - Dan L. Duncan Comprehensive Cancer Center

Houston, TX

Open and Accepting

Virginia

UVA Cancer Center University of Virginia Health System

Charlottesville, VA

Open and Accepting

Virginia Commonwealth University Medical Center

Richmond, VA

Open and Accepting
Interested in this trial?
  • Call us today 😀 keyboard_arrow_right

    We know how difficult and confusing this process can be. If you are interested in this clinical trial or have questions, you can call us at any time. You can also send us a direct message with questions.

    (888) 828-2206
  • If you are interested in keeping an eye on this trial, you can add it to your list of favorite trials. We'll send you alerts when this trial is updated.

  • Talk to your doctor keyboard_arrow_right

    You can print an overview of this trial to take in to your next appointment. Your doctor can help you understand if this trial may be right for you.

Still need help? Send us a message