Clinical Trial: Fludarabine Phosphate, Low-Dose Total Body Irradiation, and Donor Stem Cell Transplant in Treating Patients With Hematologic Malignancies or Kidney Cancer

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

Official Title: Low-Dose TBI and Fludarabine Followed by Unrelated Donor Stem Cell Transplantation for Patients With Hematologic Malignancies and Renal Cell Carcinoma - A Multi-center Trial

Brief Summary: This clinical trial studies fludarabine phosphate, low-dose total body irradiation, and donor stem cell transplant in treating patients with hematologic malignancies or kidney cancer. Giving chemotherapy drugs, such as fludarabine phosphate, and total-body irradiation before a donor peripheral blood stem cell transplant helps 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). Giving an infusion of the donor's T cells (donor lymphocyte infusion) after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine before the transplant and cyclosporine and mycophenolate mofetil after the transplant may stop this from happening.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To determine whether stable allogeneic engraftment from unrelated hematopoietic stem cell donors can be safely established using a non-myeloablative conditioning regimen in patients with hematologic malignancies and renal cell carcinoma.

SECONDARY OBJECTIVES:

I. To evaluate whether donor lymphocyte infusion (DLI) can be safely used in patients with mixed or full donor chimerism to eliminate persistent or progressive disease.

OUTLINE:

CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) on days -4 to -2. Patients also undergo low-dose total-body irradiation (TBI) on day 0.

TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell (PBSC) or bone marrow transplantation on day 0.

IMMUNOSUPPRESSION: Patients receive cyclosporine orally (PO) twice daily (BID) on days -3 to 100 with taper to day 177 and mycophenolate mofetil PO BID on days 0-40 with taper to day 96. Patients with mixed chimerism, persistent or progressive disease, and no evidence of graft-versus-host disease and who have been off immunosuppression for at least 2 weeks undergo DLI over 30 minutes. DLI may be repeated every 65 days for up to 3 doses.

After completion of study treatment, patients are follow-up periodically for 5 years.


Sponsor: Fred Hutchinson Cancer Research Center

Current Primary Outcome: Establishment of an allograft as defined by stable mixed chimerism or full donor chimerism [ Time Frame: At day 56 ]

Engraftment will be assessed separately among patients who receive bone marrow and patients who receive PBSC. Patients with low-risk and high-risk disease will be assessed separately.


Original Primary Outcome:

Current Secondary Outcome:

  • Disease-free survival [ Time Frame: Up to 200 days ]
    Will be summarized.
  • Relapse [ Time Frame: Assessed up to 5 years ]
    Will be summarized.
  • Disease-related mortality [ Time Frame: Before day 200 ]
    Will be summarized.
  • Response of malignancy to DLI [ Time Frame: Assessed up to 5 years ]
    Examined and reported in a descriptive manner and confidence intervals will be presented for all estimates. Analyses will be conducted separately among the low- and high-risk groups.
  • Incidence of myelosuppression [ Time Frame: Greater than 2 days after initial PBSC infusion ]
    Absolute neutrophil count (ANC) less than 500/ul for more than 2 days, platelets less than 20,000/ul for more than 2 days. Examined and reported in a descriptive manner and confidence intervals will be presented for all estimates. Analyses will be conducted separately among the low- and high-risk groups.
  • Incidence of aplasia after DLI [ Time Frame: Greater than 2 days after initial PBSC infusion ]
    Examined and reported in a descriptive manner and confidence intervals will be presented for all estimates. Analyses will be conducted separately among the low- and high-risk groups.
  • Incidence of grades 2-4 acute GVHD after DLI [ Time Frame: Until day 90 ]
    Examined and reported in a descriptive manner and confidence intervals will be presented for all estimates. Analyses will be conducted separately among the low- and high-risk groups.
  • Incidence of grades 2-4 acute GVHD after PBSC infusion [ Time Frame: Up to day 177 ]
    Examined and reported in a descriptive manner and confidence intervals will be presented for all estimates. Analyses will be conducted separately among the low- and high-risk groups.
  • Incidence of grades 2-4 chronic extensive GVHD after DLI [ Time Frame: Assessed up to 5 years ]
    Examined and reported in a descriptive manner and confidence intervals will be presented for all estimates. Analyses will be conducted separately among the low- and high-risk groups.
  • Dose of CD3+ required to convert mixed to full lymphoid chimeras [ Time Frame: Day 28 post-transplant ]
    Examined and reported in a descriptive manner and confidence intervals will be presented for all estimates. Analyses will be conducted separately among the low- and high-risk groups.
  • Dose of CD3+ required to convert mixed to full lymphoid chimeras [ Time Frame: Day 56 post-transplant ]
    Examined and reported in a descriptive manner and confidence intervals will be presented for all estimates. Analyses will be conducted separately among the low- and high-risk groups.
  • Dose of CD3+ required to convert mixed to full lymphoid chimeras [ Time Frame: Day 84 post-transplant ]
    Examined and reported in a descriptive manner and confidence intervals will be presented for all estimates. Analyses will be conducted separately among the low- and high-risk groups.
  • Incidence of infections [ Time Frame: Assessed up to 5 years ]
    Examined and reported in a descriptive manner and confidence intervals will be presented for all estimates. Analyses will be conducted separately among the low- and high-risk groups.


Original Secondary Outcome:

Information By: Fred Hutchinson Cancer Research Center

Dates:
Date Received: June 2, 2000
Date Started: November 1999
Date Completion:
Last Updated: October 10, 2016
Last Verified: October 2016