Protocol Summary

Protocol No.: OCR40609

Sponsor Protocol No.: ACCESS

Protocol Title.: HLA-Mismatched Unrelated Donor Hematopoietic Cell Transplantation With Post-Transplantation Cyclophosphamide

Principal Investigator: Farhadfar, Nosha

Objective: 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.

Phase: Phase II

Age Group: Both

Age: 1 Year - N/A

Gender: All

Scope: National

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.

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.

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.

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.

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.

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.

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.

Detailed Eligibility:

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 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 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 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 and 3000 by solid phase immunoassay

Applicable Conditions:

  • Leukemia
  • Myelodysplastic Syndrome (MDS)
  • Stem Cell Transplant
  • Participation Institution:

  • UF Gainesville : Emma Rosenau
  • Contact:
    Emma Rosenau
    Phone: +1 352-294-8938
    Email: roseeg@ufl.edu

    More Information: View study listing on ClinicialTrials.gov http://www.clinicaltrials.gov/ct2/show/NCT04904588