Clinical Trial: Sirolimus, Cyclosporine, and Mycophenolate Mofetil in Preventing Graft-versus-Host Disease in Treating Patients With Hematologic Malignancies Undergoing Donor Peripheral Blood Stem Cell Transplant

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

Official Title: A Phase II Study to Assess Immunosuppression With Sirolimus Combined With Cyclosporine (CSP) and Mycophenolate Mofetil (MMF) for Prevention of Acute GVHD After Non-myeloablative HLA Class I or II Mism

Brief Summary: This phase II trial studies how well sirolimus, cyclosporine and mycophenolate mofetil works in preventing graft-vs-host disease (GVHD) in patients with hematologic malignancies undergoing donor peripheral blood stem cell (PBSC) transplant. Giving chemotherapy 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. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving total-body irradiation together with sirolimus, cyclosporine, and mycophenolate mofetil before and after transplant may stop this from happening.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To determine whether the incidence of acute GVHD grades II-IV can be reduced to less than the historical rate of 70% with the triple-immunosuppressant combination of cyclosporine (CSP)/mycophenolate mofetil (MMF) with sirolimus in human leukocyte antigens (HLA) class I or class II mismatched related or unrelated donor hematopoietic cell transplantation (HCT) using nonmyeloablative conditioning. The evaluation will be carried out separately among class I and class II mismatched patients.

SECONDARY OBJECTIVES:

I. To evaluate the incidence of non-relapse mortality before day 100.

II. To evaluate the incidences of grades III-IV acute GVHD.

OUTLINE:

CONDITIONING: Patients receive fludarabine phosphate intravenously (IV) over 30 minutes on days -4 to -2. Patients also undergo total-body irradiation on day 0.

TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation.

IMMUNOSUPPRESSION: Patients receive sirolimus orally (PO) once daily (QD) on days -3 to 180 with taper to day 365; cyclosporine PO twice daily (BID) on days -3 to 150 with taper to day 180; and mycophenolate mofetil PO thrice daily (TID) on days 0-30 and then BID to day 100 with taper to day 150.

After completion of study treatment, patients are followed up at 6 months and every year thereafter.


Sponsor: Fred Hutchinson Cancer Research Center

Current Primary Outcome: Rate of grade II-IV acute GVHD in HLA class I or II mismatched nonmyeloablative transplants [ Time Frame: By day 100 ]

Original Primary Outcome: Efficacy of CSP, MMF and sirolimus in reducing the rate of grade II-IV acute GVHD in HLA class I or II mismatched nonmyeloablative transplants [ Time Frame: By day 100 ]

Current Secondary Outcome: Rate of grade III-IV acute GVHD [ Time Frame: By day 100 ]

Original Secondary Outcome:

  • Grade III-IV acute GVHD [ Time Frame: By day 100 ]
  • Non-relapse mortality [ Time Frame: Before day 100 ]


Information By: Fred Hutchinson Cancer Research Center

Dates:
Date Received: November 29, 2010
Date Started: December 2010
Date Completion:
Last Updated: November 3, 2016
Last Verified: November 2016