Clinical Trial: Autologous Stem Cell Transplant Followed by Donor Stem Cell Transplant in Treating Patients With Relapsed or Refractory Lymphoma

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Phase I/II Study of Autologous Stem Cell Transplantation Followed by Nonmyeloablative Allogeneic Stem Cell Transplantation for Patients With Relapsed or Refractory Lymphoma - A Multi-center Trial

Brief Summary: This phase I/II trial studies how well autologous stem cell transplant followed by donor stem cell transplant works in treating patients with lymphoma that has returned or does not respond to treatment. Peripheral blood stem cell transplant using stem cells from the patient or a donor may be able to replace immune cells that were destroyed by chemotherapy used to kill cancer cells. The donated stem cells may also help destroy any remaining cancer cells (graft-versus-tumor effect).

Detailed Summary:

PRIMARY OBJECTIVES:

I. To evaluate engraftment of human leukocyte antibody (HLA) identical peripheral blood stem cell (PBSC) allografts given after conditioning with total-body irradiation (TBI) (200cGy) +/- fludarabine (fludarabine phosphate), 90 mg/m^2 and post-grafting immunosuppression with cyclosporine (CSP)/mycophenolate mofetil (MMF) in refractory or relapsed lymphoma patients following an initial autologous peripheral blood stem cell transplant (PBSCT) for disease cytoreduction.

II. To determine the non-relapse mortality at day 100 post-non-myeloablative allografting following mobilization and high-dose chemotherapy with autografting.

SECONDARY OBJECTIVES:

I. To determine the disease free survival and overall survival of non-myeloablative allografting following autologous PBSCT.

OUTLINE:

CONDITIONING REGIMEN: Patients with matched, related stem cell donors receive cyclophosphamide intravenously (IV) on days -6 and -5 and undergo TBI twice daily (BID) on days -3 to -1. Patients with matched, unrelated stem cell donors receive carmustine IV over 3 hours on day -7, etoposide IV over 2 hours BID on days -6 to -3, and cytarabine IV over 3 hours BID on days -6 to -3, and melphalan IV over 30 minutes on day -2.

TRANSPLANTATION: All patients undergo autologous PBSCT on day 0.

NON-MYELOABLATIVE CONDITIONING: Beginning 40-120 days following PBSC transplant, patients with related donors undergo TBI on day 0. Patients with unrelated donors receive fludarabine phosphate IV over 30 minutes on days -4 to -2 and undergo TBI on day 0. Sponsor: Fred Hutchinson Cancer Research Center

Current Primary Outcome:

  • Engraftment of HLA identical PBSC allografts [ Time Frame: Day 56 ]
    The rates and accompanying confidence intervals associated with failure of engraftment at day +56 will be calculated after every 5th patient is enrolled on the study. If the lower limit to the appropriate one-sided 80% confidence interval exceeds 25%, this will be considered sufficient evidence of an excess "failure" rate and the study will be stopped. For these purposes, all patients will be evaluated together (patients with chemosensitive and chemoresistant disease).
  • Non-relapse mortality [ Time Frame: Day 100 post-non-myeloablative allografting following mobilization and high-dose chemotherapy with autografting ]
    The rates and accompanying confidence intervals associated with transplant-related mortality will be calculated after every 5th patient is enrolled on the study. If the lower limit to the appropriate one-sided 80% confidence interval exceeds 25%, this will be considered sufficient evidence of an excess "failure" rate and the study will be stopped. For these purposes, all patients will be evaluated together (patients with chemosensitive and chemoresistant disease).


Original Primary Outcome:

Current Secondary Outcome:

  • Overall survival (OS) [ Time Frame: From the date of autologous transplant until the time of death, assessed up to 17 years ]
    Though OS will be analyzed for the trial as a whole, chemosensitive and chemoresistant patients will be analyzed separately for OS for comparison to their respective historical controls. These groups will be looked at separately to gather preliminary data on whether or not there appears to be a difference in the OS among patients who had chemosensitive vs chemoresistant disease.
  • Progression free-survival (PFS) [ Time Frame: From the date of autologous transplant until the time of progression, relapse, death, or the date the patient was last known to be in remission, assessed at 3 years ]
    Though PFS will be analyzed for the trial as a whole, chemosensitive and chemoresistant patients will be analyzed separately for PFS for comparison to their respective historical controls. These groups will be looked at separately to gather preliminary data on whether or not there appears to be a difference in the PFS among patients who had chemosensitive vs chemoresistant disease.


Original Secondary Outcome:

Information By: Fred Hutchinson Cancer Research Center

Dates:
Date Received: June 2, 2000
Date Started: September 1999
Date Completion:
Last Updated: February 23, 2016
Last Verified: February 2016