Clinical Trial: Haploidentical BMT With Post-Transplant Cyclophosphamide and Bendamustine

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Phase I/II Study of Haploidentical Bone Marrow Transplant With Post-Transplant Cyclophosphamide and/or Bendamustine

Brief Summary:

The purpose of this study is to evaluate the safety and efficacy of substituting day +4 cyclophosphamide with post-transplant bendamustine in myeloablative (MAC) or reduced intensity conditioning (RIC) haploidentical hematopoietic cell transplantation (HHCT) for advanced leukemia and lymphoma patients.

The phase I component of the study is to evaluate the safety of completely substituting the second dose of post-transplant cyclophosphamide (PT-CY) given on day +4 with bendamustine (PT-BEN).

The phase II component of the study will continue to evaluate the safety and efficacy of subjects who receive PT-CY on day +3 and PT-BEN on day +4.

Approximately, a total of 32 subjects will be treated under this protocol. Approximately 12 to 15 subjects will be used as control, subjects that receive no PT-BEN, for direct comparison.


Detailed Summary:

This study will follow the standard-of-care bone marrow transplant (BMT), with the only exception being to gradually substitute post-transplant cyclophosphamide (on day +4 after BMT) with bendamustine. Three dose levels are planned for the phase I component of the study, consisting of a combination of sequentially reduced doses of cyclophosphamide and increased doses of bendamustine (on day +4 after BMT) with the full dose cyclophosphamide on day +3 after BMT remaining unchanged.

Control patients will be patients that have declined to participate in the main trial but will receive haploidentical BMT with the current standard of two days of PT-CY (and no PT-BEN) and will be consented for the immune monitoring studies only.


Sponsor: University of Arizona

Current Primary Outcome: Safety in regards to engraftment, incidence and grade of acute and chronic graft versus host disease and toxicity/non-relapse mortality post-haploidentical bone marrow transplantation. [ Time Frame: Change from baseline to 3 years ]

Safety of haploidentical BMT using a preparative regimen of Busulfan Fludarabine and Melphalan, or Total Body Irradiation and Fludarabine followed by PT-CY and/or PT-BEN. Demonstrate that this regimen is well tolerated and will not result in unacceptable rates of high-grade acute or chronic graft vs host disease (GvHD), graft failure, non-relapse mortality (NRM) or relapse compared to published data with PT-CY.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Incidence of regimen-related organ toxicities [ Time Frame: Change from baseline to 3 years ]
  • Severity of regimen-related organ toxicities [ Time Frame: Change from baseline to 3 years ]
  • Incidence of acute GvHD [ Time Frame: Change from baseline to 3 years ]
  • Severity of acute GvHD [ Time Frame: Change from baseline to 3 years ]
  • Incidence of chronic GvHD [ Time Frame: Change from baseline to 3 years ]
  • Extent of chronic GvHD [ Time Frame: Change from baseline to 3 years ]
  • Incidence of graft failure [ Time Frame: Change from baseline to 3 years ]
  • Level of donor cell engraftment [ Time Frame: Change from baseline to 3 years ]
  • Duration of neutropenia and thrombocytopenia [ Time Frame: Change from baseline to 3 years ]
  • Severity of neutropenia and thrombocytopenia [ Time Frame: Change from baseline to 3 years ]
  • Requirement for blood product support [ Time Frame: Change from baseline to 3 years ]
    Complete blood count (CBC) will be monitored routinely and patients transfused if Hb is < 8 g/dl and platelets <20,000
  • Infection risk [ Time Frame: Change from baseline to 3 years ]
    Immune reconstitution will be studied prospectively. Viral and fungal prophylaxis and treatment will be done according to our BMT programs guidelines
  • Infection severity [ Time Frame: Change from baseline to 3 years ]
    Immune reconstitution will be studied prospectively. Viral and fungal prophylaxis and treatment will be done according to our BMT programs guidelines
  • Number of patients relapse free [ Time Frame: Change from baseline to 3 years ]
  • Overall patient survival [ Time Frame: Change from baseline to 3 years ]
  • Immune reconstitution following haploidentical BMT [ Time Frame: Change from baseline to 6 months post-BMT ]
    T cell immune reconstitution (CD4, cluster of differentiation 8 (CD8), Treg, NK), B cell and myeloid cell reconstitution will be evaluated serially until 6 months post-BMT
  • Length of stay of the protocol [ Time Frame: Change from baseline to 3 years ]
  • Cost effectiveness of the protocol [ Time Frame: Change from baseline to 3 years ]
  • Reconstituting T-cell subsets change with escalation of PT- BEN and de-escalation of day +4 PT-CY during the phase I trial [ Time Frame: Change from baseline to 3 years ]
    These effects of PT-BEN will be confirmed in all patients enrolled in the phase II component.


Original Secondary Outcome: Same as current

Information By: University of Arizona

Dates:
Date Received: December 1, 2016
Date Started: November 2016
Date Completion: April 2018
Last Updated: December 14, 2016
Last Verified: December 2016