Clinical Trial 22699

• Overview

  Study Title:

  A Phase II Study of Reduced Dose Post Transplantation Cyclophosphamide as GvHD Prophylaxis in Adult Patients with Hematologic Malignancies Receiving HLA-Mismatched Unrelated Donor Peripheral Blood Stem Cell Transplantation

  Objective:

  Primary Objective: To estimate infection-free survival (IFS) and determine safety of combination reduced-dose post-transplantation cyclophosphamide (PTCy), mycophenolate mofetil (MMF), and tacrolimus as graft-versus-host disease (GvHD) prophylaxis for patients with hematologic malignancies receiving mismatched unrelated donor (MMUD) peripheral blood stem cells (PBSC) after myeloablative (MAC) or reduced-intensity conditioning (RIC). Secondary Objective: To determine overall survival (OS), progression-free survival (PFS), infection free survival (IFS), GvHD relapse-free survival (GRFS), non-relapse mortality at 1-year post-hematopoietic cell transplant (HCT) To determine cumulative incidence and kinetics of neutrophil recovery by Day 28 To determine cumulative incidence and kinetics of platelet recovery by Day 180 To determine cumulative incidence of primary and secondary graft failure To determine donor T-cell chimerism at D28, D100 and D365 To determine cumulative incidences of acute GvHD (aGvHD) at D100 and D180 and chronic GvHD (cGvHD) at 1-year post HCT To determine cumulative incidence of grades 2-3 bacterial, fungal and viral infections at Day 100 and 1-year post HCT (per BMT CTN criteria) To determine cumulative incidence of grades 2-3 BK virus hemorrhagic cystitis at 1-year post HCT To determine cumulative incidence of relapse/progression at 1-year post-HCT To describe proportion of overall toxicity from initiation of conditioning through 1-year post-HCT To determine incidence and severity of cytokine release syndrome (CRS) within 14 days of HCT

• Treatments

  Therapies:

  Bone Marrow Transplant; Chemotherapy (NOS)

  Medications:

  Cellcept (Mycophenolate Mofetil); FK506 (Tacrolimus); Mycophenolate Mofetil (); Tacrolimus (); cyclophosphamide (); cytoxan (cyclophosphamide)

• Inclusion Criteria

  Key Inclusion Criteria:
  • Patient or legally authorized representative has the ability to provide informed consent according to the applicable regulatory and institutional requirements
  • Stated willingness to comply with all study procedures and availability for the duration of the study
  • Product planned for infusion is MMUD T-cell replete PBSC allograft
  • Cardiac function: Left ventricular ejection fraction greater than or equal to 40% based on most recent echocardiogram or MUGA results with no clinical evidence of heart failure
  • Estimated creatinine clearance greater than or equal to 45 mL/min calculated by equation
  • Pulmonary function: DLCO corrected for hemoglobin > 50% and FEV1 predicted >50% based on most recent PFT results
  • Liver function acceptable per local institutional guidelines
  • One of the following diagnoses (Stratum 1): A) Acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), or other acute leukemia in 1st remission or beyond with less than or equal to 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) Patients with MDS with no circulating blasts and with > One of the following diagnoses (Stratum 2): A) Patients with acute leukemia or chronic myeloid leukemia (CML) with no circulating blasts, no evidence of extramedullary disease, and with > One of the following diagnoses (Stratum 3): Diagnosis of primary myelofibrosis with risk features making them eligible for HCT. Myelofibrosis secondary to essential thrombocythemia, polycythemia vera, or MDS with grade 4 fibrosis are also eligible. Patients with a myelofibrosis diagnosis require sponsor approval before enrolling.
  • Other criteria may apply

• Exclusion Criteria

  Key Exclusion Criteria:
  • Suitable HLA-matched related or 8/8 high-resolution matched unrelated donor available
  • Subject unwilling or unable to give informed consent, or unable to comply with the protocol including required follow-up and testing
  • Subjects with a prior allogeneic transplant
  • Subjects with an 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 a preventative GvHD and/or infectious disease prevention clinical trial
  • Subjects who undergo desensitization to reduce anti-donor HLA antibody levels prior to transplant
  • Patients who are HIV+ with persistently positive viral load. HIV-infected patients on effective anti-retroviral therapy (ART) with undetectable viral load within 6 months are eligible for this trial. Patients with well controlled HIV are eligible provided resistance panels are negative, the patient is compliant with ART, and their disease remains well controlled

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