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Clinical Trial 21186

Cancer Type: Malignant Hematology
Study Type: Treatment
NCT#: NCT04904588

Phase: Phase II
Principal Investigator: Khimani, Farhad

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Overview

Study Title

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

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.

Objective

Primary Objective: To determine OS at one year following transplantation of a PBSC product from a MMUD using PTCy based GVHD prophylaxis Secondary Objectives: To determine the incidence of CRS within 14 days of HCT To determine event-free survival (EFS) at 1-year (events include graft failure, relapse, death, National Institutes of Health [NIH]-severe cGvHD, and grade 3-4 aGvHD. To determine GRFS and modified GRFS (mGRFS) at 1-year post-HCT To determine progression-free survival (PFS) at 1-year post-HCT To determine NRM at Day+100 and 1-year post-HCT To determine EFS and OS at 1 year based on donor HLA Match grade and donor age (7/8 versus <7/8) To determine cumulative incidence and kinetics of neutrophil recovery To determine cumulative incidence and kinetics of platelet recovery To determine cumulative incidence of primary and secondary graft failure To determine donor chimerism at day +100 (Strata 2 and 3) To determine cumulative incidences of aGVHD and cGVHD To determine cumulative incidence of relapse/progression To determine cumulative incidence of BK and CMV viral infections

Treatments

Therapies

Chemotherapy (NOS); Radiotherapy; Therapy (NOS)

Medications

Alkeran (Melphalan); Cellcept (Mycophenolate Mofetil); FK506 (Tacrolimus); MESNA (); Melphalan (); Mycophenolate Mofetil (); Tacrolimus (); busulfan (); cyclophosphamide (); cytoxan (cyclophosphamide); fludarabine (Fludarabine phosphate)

Inclusion Criteria

Stratum 1 Recipient Inclusion Criteria:

  • 18-66 years of age (chemotherapy-based conditioning) or > Planned MAC regimen as defined per protocol
  • Available partially HLA-MMUD (4/8-7/8 at HLA-A, -B, -C, and -DRB1 is required) with age > Product planned for infusion is PBSC
  • HCT Comorbidity Index (HCT-CI) > One of the following diagnoses: (a) 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. (b) 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. (c) Patients with myelodysplastic syndrome (MDS) with no circulating blasts and with > Cardiac function: Left ventricular ejection fraction > 45% based on most recent echocardiogram or multigated acquisition scan (MUGA) results
  • Adequate organ function
  • Karnofsky performance status (KPS) of > 70% Stratum 2 Recipient Inclusion Criteria
  • Age > 18 years at the time of signing informed consent
  • Planned NMA/RIC regimen as defined per protocol
  • Available partially HLA-MMUD (4/8-7/8 at HLA-A, -B, -C, and -DRB1 is required) with age > Product planned for infusion is PBSC
  • One of the following diagnoses: (a) Patients with acute leukemia or chronic myelogenous leukemia (CML) with no circulating blasts, no evidence of extramedullary disease, and with > Cardiac function: Left ventricular ejection fraction > 45% based on most recent echocardiogram or MUGA results with no clinical evidence of heart failure
  • Adequate organ function
  • KPS of > 60% Stratum 3 Recipient Inclusion Criteria
  • Age > 1 years and > Partially HLA-MMUD (4/8-7/8 at HLA-A, -B, -C, and -DRB1 is required) with age > Product planned for infusion is BM
  • Planned MAC regimen as defined per protocol
  • Additional recipient and donor criteria will apply

  • Exclusion Criteria

    Recipient Exclusion Criteria (Strata 1, 2 and 3):

  • Suitable HLA-matched related or 8/8 high-resolution matched unrelated donor available
  • Unwilling or unable to give informed consent, or unable to comply with the protocol including required follow-up and testing
  • Primary myelofibrosis or myelofibrosis secondary to essential thrombocythemia, polycythemia vera, or MDS with grade 4 marrow fibrosis
  • Prior allogeneic transplant or autologous transplant within the past 3 months
  • Females who are breast-feeding or pregnant
  • Uncontrolled bacterial, viral or fungal infection at the time of the transplant preparative regimen
  • Concurrent enrollment on other interventional GVHD clinical trial (enrollment on supportive care trials may be allowed after discussion with Principal Investigators) Donor Exclusion Criteria:
  • Donor unwilling or unable to donate
  • Recipient positive anti-donor HLA antibodies against a mismatched HLA in the selected donor determined by either: (a) a positive crossmatch test of any titer (by complement-dependent cytotoxicity or flow cytometric testing) or (b) 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

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