This phase I/II trial studies whether stopping cyclosporine before mycophenolate mofetil is better at reducing the risk of life-threatening graft-versus-host disease (GVHD) than the previous approach where mycophenolate mofetil was stopped before cyclosporine. The other reason this study is being done because at the present time there are no curative therapies known outside of stem cell transplantation for these types of cancer. Because of age or underlying health status, patients may have a higher likelihood of experiencing harm from a conventional blood stem cell transplant. This study tests whether this new blood stem cell transplant method can be made safer by changing the order and length of time that immune suppressing drugs are given after transplant.
PRIMARY OBJECTIVES: I. To determine whether the incidence of life-threatening GVHD can be reduced after unrelated donor peripheral blood mononuclear cell (PBMC) hematopoietic cell transplantation (HCT) using nonmyeloablative conditioning with earlier discontinuation of cyclosporine (CSP) and extended administration of mycophenolate mofetil (MMF) in patients with hematologic malignancies and metastatic renal cell carcinoma. SECONDARY OBJECTIVES: I. To compare the incidence of acute and chronic GVHD to protocols 1463 and 1641. II. To compare the utilization of corticosteroids to protocols 1463 and 1641. III. To compare survival to that achieved under protocol 1463 and 1641. OUTLINE: CONDITIONING: Patients receive fludarabine phosphate intravenously (IV) over 30 minutes on days -4 to -2, and undergo total-body irradiation (TBI) on day 0. TRANSPLANTATION: Patients undergo allogeneic PBMC transplant on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine orally (PO) twice daily (BID) on days -3 to 80 with taper to day 150 and mycophenolate mofetil PO or IV thrice daily (TID) on days 0-30, BID on days 31-150, and then taper to day 180. Treatment continues in the absence of unacceptable toxicity. After completion of study treatment, patients are followed up periodically for 24 months and then yearly for 5 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
37
Given IV
Undergo TBI
Undergo allogeneic PBMC transplantation
Undergo allogeneic PBMC transplantation
Given PO
Given PO or IV
Correlative studies
Stanford University Hospitals and Clinics
Stanford, California, United States
Rocky Mountain Cancer Centers-Midtown
Denver, Colorado, United States
Emory University/Winship Cancer Institute
Atlanta, Georgia, United States
OHSU Knight Cancer Institute
Portland, Oregon, United States
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, United States
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States
Froedtert Memorial Lutheran Hospital, Medical College of Wisconsin
Milwaukee, Wisconsin, United States
Universitaet Leipzig
Leipzig, Germany
University of Tuebingen-Germany
Tübingen, Germany
University of Torino
Torino, Italy
Incidence of life-threatening GVHD in patients undergoing a modified taper of post-grafting immunosuppression after undergoing nonmyeloablative HSCT from matched unrelated donors
Life-threatening GVHD defined as (1) death related to GVHD or its treatment, (2) disability caused by GVHD or its treatment (3) 3 or more major infections in a calendar year or (4) suicidal ideation because of GVHD.
Time frame: 1 year
Need for corticosteroid treatment, defined as more than 1 mg/kg or equivalent of prednisone for more than 3 days at any time after transplant
Time frame: 1 year
Graft rejection
Time frame: Up to day 365
Incidence of acute and chronic GVHD
Time frame: Up to 7 years
Overall survival
Time frame: Up to 7 years
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