This phase I/II trial studies whether a new kind of blood stem cell (bone marrow) transplant, that may be less toxic, is able to treat underlying blood cancer. Stem cells are "seed cells" necessary to make blood cells. Researchers want to see if using less radiation and less chemotherapy with new immune suppressing drugs will enable a stem cell transplant to work. Researchers are hoping to see a mixture of recipient and donor stem cells after transplant. This mixture of donor and recipient stem cells is called "mixed-chimerism". Researchers hope to see these donor cells eliminate tumor cells. This is called a "graft-versus-leukemia" response.
PRIMARY OBJECTIVES: I. To determine whether stable unrelated peripheral blood stem cell (PBSC) grafts can be safely established using nonmyeloablative pretransplant conditioning with intensified post-grafting immunosuppression and with every (q) 8 hours (hr) and possibly q 6 hr mycophenolate mofetil (MMF) dosing in patients with hematologic malignancies and renal cell carcinoma. II. To determine if the incidence and severity of acute grades II-IV graft-versus-host disease (GVHD) can be reduced in patients with sustained engraftment with the use of q 8 hr MMF dosing. SECONDARY OBJECTIVES: I. To determine if engraftment can be maintained in patients with low chimerism and high risk of rejection with the use of a single dose of fludarabine (fludarabine phosphate) followed by donor lymphocyte infusion (DLI) on continued MMF/cyclosporine (CSP). II. To compare survival and disease free survival to those achieved under protocol 1463. OUTLINE: REDUCED-INTENSITY CONDITIONING: Patients receive fludarabine phosphate intravenously (IV) on days -4, -3, and -2 and undergo total-body irradiation (TBI) on day 0. TRANSPLANT: Patients undergo allogeneic peripheral blood stem cell transplant (PBSCT) 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 every 8 hours on days 0-40 with taper to day 96. After completion of study treatment, patients are followed up at 6 months, 1 year, 1.5 years, 2 years, and then annually thereafter.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
106
Given IV
Undergo TBI
Undergo nonmyeloablative PBSCT
Undergo nonmyeloablative PBSCT
Given PO
Given PO
University of Arizona Health Sciences Center
Tucson, Arizona, United States
Stanford University Hospitals and Clinics
Stanford, California, United States
Emory University/Winship Cancer Institute
Atlanta, Georgia, United States
OHSU Knight Cancer Institute
Portland, Oregon, United States
Baylor Medical Center at Garland
Garland, Texas, 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 and the Medical College of Wisconsin
Milwaukee, Wisconsin, United States
Universitaet Leipzig
Leipzig, Germany
University of Torino
Torino, Italy
Risk of true graft rejection in patients with and without preceding chemotherapy
The goal is to reduce the risk in patients without preceding chemotherapy to \< 20% and with preceding chemotherapy to \< 10%.
Time frame: Up to 5 years
Risk of grades II-IV acute GVHD in those patients with sustained engraftment
The goal is to reduce the incidence of grades II-IV acute GVHD from 50% to less than 35% in patients with sustained engraftment by increasing the dosing of MMF to every 8 hours. The impact of the enhanced post-grafting immunosuppression on objective measures of GVHD will be described. These include doses and duration of immunosuppression (in particular corticosteroids) and number of GVHD treatment regimens used within the first year. These parameters will be compared to the results of protocol 1463.
Time frame: Up to 5 years
Incidence of reversing impending graft rejection (less than 40% donor cluster of differentiation [CD]3+ T cell chimerism)
The secondary objective of reversing pending graft rejection with fludarabine phosphate and DLI will be evaluated in the context of overall engraftment. The number of patients given DLI in this context is expected to be small. The response to DLI will be followed and reported in a descriptive manner. The effect of this intervention on adverse outcomes will be followed.
Time frame: Up to 5 years
Overall survival
Time frame: Up to 5 years
Progression-free survival
Time frame: Up to 5 years
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.