Clinical Trial: Reduced Intensity Chemotherapy and Radiation Therapy Before Donor Stem Cell Transplant in Treating Patients With Hematologic Malignancies

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

Official Title: A Two Step Approach to Non-Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation for Patients With Hematologic Malignancies

Brief Summary: This clinical trial studies the use of reduced intensity chemotherapy and radiation therapy before donor stem cell transplant in treating patients with hematologic malignancies. Giving low doses of chemotherapy, such as cyclophosphamide and fludarabine phosphate, before a donor stem cell transplant may help stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Reducing the intensity of the chemotherapy and radiation may also reduce the side effects of the donor stem cell transplant.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To demonstrate efficacy of this approach over the historical 2 step reduced intensity conditioning (RIC) approaches in the "vulnerable" population defined as: patients with hematopoietic cell transplant (HCT)-co-morbidity index (CI)/age scores >= 2, but no more than a score of 5 as based on the Sorror et al. data.

SECONDARY OBJECTIVES:

I. To compare the non-relapse mortality (NRM) and relapse related mortality (RRM) rates at 1 year for patients treated on this study to the that of patients undergoing haploidentical RIC hematopoietic stem cell transplantation (HSCT) as reported in the literature and as observed in the 2 step RIC trials.

II. To determine the incidence and severity of graft-versus-host disease (GVHD) in patients undergoing treated on the Thomas Jefferson University (TJU) RIC 2 step approach.

III. To evaluate engraftment rates and lymphoid reconstitution in patients treated on the TJU RIC 2 step approach.

OUTLINE:

RIC: Patients receive fludarabine phosphate intravenously (IV) over 60 minutes on days -10 to -8 and cyclophosphamide IV over 2 hours on days -3 and -2. Patients also undergo total body irradiation (TBI) followed by a donor lymphocyte infusion (DLI) on day -6.

TRANSPLANT: Patients undergo cluster of differentiation (CD)34+ peripheral blood stem cell transplant on day 0.

GVHD PROPHYLAXIS: Patients receive tacrolimus orally (PO) beginning day -1 with a taper initiated on day 42 and mycophenolate mofetil IV twice daily (BID)
Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University

Current Primary Outcome: Overall Survival (OS) [ Time Frame: At 1 year post HSCT ]

OS will be estimated using Kaplan-Meier curves. The 1-year OS rate and corresponding 95% confidence interval will be estimated from the Kaplan-Meier curve for the OS.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Relapse Related Mortality (RRM) [ Time Frame: At 1 year post HSCT ]
    Will be reported descriptively. RRM may also be estimated using Kaplan Meier curves and/or cumulative incidence analyses.
  • Non-Relapse Mortality (NRM) [ Time Frame: At 1 year post HSCT ]
    Will be reported descriptively. NRM may also be estimated using Kaplan Meier curves and/or cumulative incidence analyses.
  • Incidence and severity of GVHD [ Time Frame: Up to 1 year post HSCT ]
    Will be reported descriptively
  • Engraftment rates [ Time Frame: Up to 1 year post HSCT ]
    Will be reported descriptively
  • Lymphoid reconstitution [ Time Frame: Up to 1 year post HSCT ]
    Lymphoid reconstitution will be evaluated monthly to every other month during the first year post HSCT and will be reported descriptively.


Original Secondary Outcome: Same as current

Information By: Thomas Jefferson University

Dates:
Date Received: September 30, 2015
Date Started: November 2015
Date Completion:
Last Updated: October 18, 2016
Last Verified: October 2016