Standard versus Low Dose Cyclophosphamide for Prevention of GVHD and Improvement in Quality of Life after Donor Stem Cell Transplant among Older Adults with Hematological Cancers

PRIMARY OBJECTIVE:

I. To compare health-related quality of life at three months post allogeneic hematopoietic stem cell transplant (HCT) between recipients receiving attenuated versus high dose of post-transplant cyclophosphamide (PTCy) in addition to two drug graft-versus-host disease (GVHD) prophylaxis.

SECONDARY OBJECTIVES:

I. To compare functional outcomes at three months post-HCT in recipients of attenuated versus high dose of PTCy in addition to two-drug GVHD prophylaxis.

II. To compare graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS) at one year post-HCT among the two treatment arms.

III. To compare overall survival (OS) and event-free survival (EFS) at one year post-HCT among the two treatment arms.

IV. To determine the cumulative incidence of disease relapse and transplant-related mortality (TRM) at one year among the two treatment arms.

V. To determine the cumulative incidence of grade II-IV acute GVHD at one year among the two treatment arms, according to the Mount Sinai acute GVHD grading system.

VI. To determine the cumulative incidence of chronic GVHD of different grades at one year among the two treatment arms, according to the National Institutes of Health (NIH) chronic GVHD grading system.

VII. To determine the cumulative incidence and kinetics of hematologic recovery (neutrophil and platelet) among the two treatment arms.

VIII. To determine the incidence of adverse events grade III or higher among the two treatment arms, according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

IX. To determine the cumulative incidence of grade II or higher infections at 6 months among the two treatment arms per the Bone Marrow Transplant (BMT) Clinical Trial Network (CTN) criteria.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive the standard dose of cyclophosphamide intravenously (IV), over 2 hours, on days + 3 and +4, as well as sirolimus orally (PO) and mycophenolate mofetil PO per standard of care in the absence of disease progression or unacceptable toxicity. Patients optionally undergo blood sample collection throughout the study.

ARM II: Patients receive a lower dose of cyclophosphamide IV, over 2 hours, on days + 3 and +4, as well as sirolimus PO and mycophenolate mofetil PO per standard of care in the absence of disease progression or unacceptable toxicity. Patients optionally undergo blood sample collection throughout the study.

After completion of study treatment, patients are followed up at day +30, +90 and +365.