Clinical Trial: A Two-Step Approach to Reduced Intensity Bone Marrow Transplant for Patients With Hematological Malignancies

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

Official Title: A Two Step Approach to Reduced Intensity Allogeneic Hematopoietic Stem Cell Transplantation for Patients With Hematologic Malignancies

Brief Summary: The purpose of this research study is to compare the survival rates of patients with better risk disease undergoing hematopoietic stem cell transplant (HSCT) to the survival rates reported in the medical literature of similar patients undergoing reduced intensity HSCT from matched related donors.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To compare the overall survival (OS) rate at 2 years post treatment using the Jefferson 2 step reduced intensity conditioning (RIC) approach in patients with haploidentical family donors with hematological malignancies in morphological or radiographic remission or with chemosensitive, indolent diseases to historical OS rates in similar populations after RIC matched donor HSCT as reported in the literature.

SECONDARY OBJECTIVES:

I. To compare the treatment-related mortality (TRM) rate at 2 years for patients treated on this study to the historical TRM rates of patients undergoing RIC matched-sibling HSCT as reported in the literature.

II. To compare the 2 year relapse rates and relapse related mortality of patients with myeloid diseases to that of patients with lymphoid diseases who are treated on this Thomas Jefferson University (TJU) RIC 2 step approach.

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

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

V. To evaluate the incidence of TRM at 100 days in patients treated on the TJU RIC 2 step approach.

OUTLINE:

REDUCED INTENSITY CONDITIONING: Patients receive fludarabine phosphate intravenously (IV) over 60 minutes on days -11 to -8 and bulsufan IV over 3 hours on days -10 to -9. Patients undergo total body irradiation (TBI) on day -6. Patients also rec
Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University

Current Primary Outcome: Overall Survival (OS) in patients with haploidentical family donors with hematological malignancies in morphological or radiographic remission or with chemosensitive, indolent diseases [ Time Frame: At 2 years ]

The primary null hypothesis is that 2 year OS rate is at most 35%. This hypothesis will be rejected if the 95% confidence interval for year OS rate computed from the estimated Kaplan-Meier survival curves will be entirely above 0.35.


Original Primary Outcome: Overall Survival (OS) [ Time Frame: At 2 years post-treatment ]

Compare OS rate using Two Step approach in patients with haploidentical family donors to reported historical OS rates in similar populations after reduced intensity conditioning (RIC) mated donor hematopoietic stem cell transplant (HSCT)

  • OS of < 35% at 2 years would demonstrate poor efficacy for the TJU 2 Step haploidentical regimen as compared to regimens using matched related and unrelated donors
  • OS of ≥60% at 2 years would demonstrate that the TJU 2 Step haploidentical RIC regimen is equal or superior to those using matched related or unrelated donors


Current Secondary Outcome:

  • Treatment Related Mortality (TRM) [ Time Frame: At 2 years ]
    To compare the treatment related mortality rate (TRM) for patients treated on this study to the historical TRM rates of patients undergoing reduced intensity conditioning (RIC) matched-sibling hematopoietic stem cell transplant (HSCT) as reported in the literature
  • Incidence and severity of GVHD, graded according to standard criteria [ Time Frame: Assessed up to 2 years ]
    The estimates of incidence rates will be presented with corresponding 95% confidence intervals using the exact method
  • Relapse Rate [ Time Frame: At 2 years ]
    Evaluated by estimating Kaplan-Meier survival curves. From these curves, the 95% confidence interval for 2 year rates will be computed.
  • Engraftment Rates [ Time Frame: Assessed up to 2 years ]
    The estimates of incidence rates will be presented with corresponding 95% confidence intervals using the exact method.
  • Incidence of Treatment Related Mortality (TRM) [ Time Frame: At 100 days ]
    The estimates of incidence rates will be presented with corresponding 95% confidence intervals using the exact method.
  • Relapse Related Mortality [ Time Frame: At 2 years ]
    Evaluated by estimating Kaplan-Meier survival curves. From these curves, the 95% confidence interval for 2 year rates will be computed.
  • Lymphoid Reconstitution [ Time Frame: 100 days post-transplant ]
    To evaluate lymphoid reconstitution in patients treated on the Two Step approach


Original Secondary Outcome:

  • Treatment Related Mortality (TRM) [ Time Frame: At 2 years ]
    To compare the treatment related mortality rate (TRM) for patients treated on this study to the historical TRM rates of patients undergoing reduced intensity conditioning (RIC) matched-sibling hematopoietic stem cell transplant (HSCT) as reported in the literature
  • Graft versus Host Disease (GVHD) [ Time Frame: At 1 and 3 years ]
    To determine the incidence and severity of graft-versus-host disease (GVHD) in patients undergoing treated on the TJU Two Step approach
  • Relapse Rate [ Time Frame: At 2 years ]
    To compare the relapse rates of patients with myeloid diseases to that of patients with lymphoid diseases who are treated on this Two Step approach
  • Engraftment Rates [ Time Frame: 100 days post-transplant ]
    To evaluate engraftment rates in patients treated on the Two Step approach
  • Incidence of Treatment Related Mortality (TRM) [ Time Frame: At 100 days ]
    To evaluate the incidence of TRM at 100 days in patients treated on the Two Step approach
  • Relapse Related Mortality [ Time Frame: At 2 years ]
    To compare the relapse related mortality of patients with myeloid diseases to that of patients with lymphoid diseases who are treated on this Two Step approach
  • Lymphoid Reconstitution [ Time Frame: 100 days post-transplant ]
    To evaluate lymphoid reconstitution in patients treated on the Two Step approach


Information By: Thomas Jefferson University

Dates:
Date Received: June 27, 2011
Date Started: August 2011
Date Completion: July 2019
Last Updated: October 18, 2016
Last Verified: October 2016