Tacrolimus and Mycophenolate Mofetil With or Without Sirolimus in Preventing Acute Graft-Versus-Host Disease in Patients Who Are Undergoing Donor Stem Cell Transplant for Hematologic Cancer
Summary
This randomized phase II trial is studying how well giving tacrolimus and mycophenolate mofetil (MMF) together with or without sirolimus works in preventing acute graft-versus-host disease (GVHD) in patients undergoing donor stem cell transplant for hematologic cancer. Giving low doses of chemotherapy, such as fludarabine phosphate, and total-body-irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving MMF and tacrolimus with or without sirolimus after transplant may stop this from happening
Description
PRIMARY OBJECTIVES:
I. To determine which of 3 GVHD prophylaxis regimens results in reduction of acute grades II-IV GVHD to =< 40%.
SECONDARY OBJECTIVES:
I. Reduce the incidence of non-relapse mortality from infections and GVHD before day 200 to =< 15%.
II. Reduce the utilization of high-dose corticosteroids compared to protocols 1463, 1641, and 1668.
III. Compare survival and progression-free survival to that achieved under protocols 1463, 1641, and 1668.
OUTLINE:
CONDITIONING: All patients receive fludarabine phosphate intravenously (IV) over 30 minutes on days -4 to -2 and undergo total-body irradiation on day 0.
TRANSPLANTATION: All patients undergo allogeneic peripheral blood stem cell transplantation on day 0.
IMMUNOSUPPRESSION: Patients are randomized to 1 of 3 treatment arms.
ARM I: Patients receive tacrolimus IV or orally (PO) every 12 hours on days -3 to 180 with taper beginning on day 100 in the absence of GVHD. Patients also receive MMF PO every 8 hours on days 0-29 and then every 12 hours on days 30-96 with taper beginning on day 40 in the absence of GVHD.
ARM II: Patients receive tacrolimus IV or PO every 12 hours on days -3 to 150 with taper beginning on day 100 in the absence of GVHD. Patients also receive MMF PO every 8 hours on days 0-29 and then every 12 hours on days 30-180 with taper beginning on day 150 in the absence of GVHD.
ARM III: Patients receive tacrolimus and MMF as in arm II. Patients also receive sirolimus PO once daily on days -3 to 80.
After completion of study treatment, patients are followed up at 6 months and then every year thereafter.
Study Design
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Conditions
Accelerated Phase Chronic Myelogenous Leukemia
Intervention
mycophenolate mofetil, fludarabine phosphate, tacrolimus, peripheral blood stem cell transplantation, total-body irradiation, sirolimus, laboratory biomarker analysis, polymerase chain reaction, allogeneic hematopoietic stem cell transplantation
Location
Presbyterian - Saint Lukes Medical Center - Health One
Denver
Colorado
United States
80218
Status
Active, not recruiting
Source
Fred Hutchinson Cancer Research Center
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00105001
- Information obtained from ClinicalTrials.gov on May 19, 2013
Medical and Biotech [MESH] Definitions
Peripheral Blood Stem Cell Transplantation
Transplantation of stem cells collected from the peripheral blood. It is a less invasive alternative to direct marrow harvesting of hematopoietic stem cells. Enrichment of stem cells in peripheral blood can be achieved by inducing mobilization of stem cells from the BONE MARROW.
Tacrolimus Binding Protein 1a
A 12-KDa tacrolimus binding protein that is found associated with and may modulate the function of calcium release channels. It is a peptidyl-prolyl cis/trans isomerase which is inhibited by both tacrolimus (commonly called FK506) and SIROLIMUS.
Hematopoietic Stem Cell Mobilization
The release of stem cells from the bone marrow into the peripheral blood circulation for the purpose of leukapheresis, prior to stem cell transplantation. Hematopoietic growth factors or chemotherapeutic agents often are used to stimulate the mobilization.
Tacrolimus Binding Proteins
A family of immunophilin proteins that bind to the immunosuppressive drugs TACROLIMUS (also known as FK506) and SIROLIMUS. EC 5.2.1.-
Cord Blood Stem Cell Transplantation
Transplantation of STEM CELLS collected from the fetal blood remaining in the UMBILICAL CORD and the PLACENTA after delivery. Included are the HEMATOPOIETIC STEM CELLS.
Clinical Trials
RATIONALE: Giving low doses of chemotherapy, such as fludarabine, and radiation therapy before a donor bone marrow or stem cell transplant helps stop the growth of cancer cells. It also st...
Peripheral Stem Cell Transplantation in Treating Patients With Metastatic or Recurrent Kidney Cancer
RATIONALE: Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy and radiation therapy used to kill cancer cells. Sometimes the trans...
RATIONALE: Giving low doses of chemotherapy, such as fludarabine, and radiation therapy before a donor stem cell transplant helps stop the growth of cancer cells. It also stops the patient...
RATIONALE: Peripheral stem cell or bone marrow transplantation may be able to replace immune cells that were destroyed by chemotherapy or radiation therapy used to kill tumor cells. Someti...
RATIONALE: Monoclonal antibodies such as daclizumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Peripheral stem ce...
PubMed Articles
Purpose The pharmacokinetics of both tacrolimus and mycophenolic acid in renal transplant recipients on a corticosteroid-free regimen was evaluated. Methods Upon administration of steady-state mornin...
Long-term results of prospective randomized trials comparing triple immunosuppressive strategies combining tacrolimus (TAC) or cyclosporine A (CsA) with mycophenolate mofetil (MMF) and steroids after...
Miles CD, Skorupa JY, Sandoz JP, Rigley TH, Nielsen KJ, Stevens RB. Albuminuria after renal transplantation: maintenance with sirolimus/low-dose tacrolimus vs. mycophenolate mofetil/high-dose tacrolim...
In the current study, we evaluated a combination of tacrolimus and mycophenolate mofetil (MMF) as GvHD prophylaxis in 50 patients undergoing truly nonmyeloablative (NM; 90 mg/m(2) fludarabine, 2 Gy TB...
Mycophenolate mofetil may be effective in CNS sarcoidosis but not in sarcoid myopathy.
To describe effectiveness, steroid-sparing effect, and tolerance of the antiproliferative immunosuppressant mycophenolate mofetil (MMF) in neurosarcoidosis.
