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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
55
Given IV
Undergo low-dose TBI
Undergo nonmyeloablative HSCT
Undergo nonmyeloablative allogeneic bone marrow transplantation
Undergo nonmyeloablative allogeneic PBSC transplantation
Undergo DLI
Given PO
Given PO
Correlative studies
Correlative studies
City of Hope Medical Center
Duarte, California, United States
Stanford University Hospitals and Clinics
Stanford, California, United States
University of Colorado
Denver, Colorado, United States
Baylor University Medical Center
Dallas, 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
Universitaet Leipzig
Leipzig, Germany
Establishment of an allograft as defined by stable mixed chimerism or full donor chimerism
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.
Time frame: At day 56
Disease-free survival
Will be summarized.
Time frame: Up to 200 days
Relapse
Will be summarized.
Time frame: Assessed up to 5 years
Disease-related mortality
Will be summarized.
Time frame: Before day 200
Response of malignancy to DLI
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.
Time frame: Assessed up to 5 years
Incidence of myelosuppression
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.
Time frame: Greater than 2 days after initial PBSC infusion
Incidence of aplasia after DLI
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.
Time frame: Greater than 2 days after initial PBSC infusion
Incidence of grades 2-4 acute GVHD after DLI
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.
Time frame: Until day 90
Incidence of grades 2-4 acute GVHD after 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.
Time frame: Up to day 177
Incidence of grades 2-4 chronic extensive GVHD after DLI
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.
Time frame: Assessed up to 5 years
Dose of CD3+ required to convert mixed to full lymphoid chimeras
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.
Time frame: Day 28 post-transplant
Dose of CD3+ required to convert mixed to full lymphoid chimeras
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.
Time frame: Day 56 post-transplant
Dose of CD3+ required to convert mixed to full lymphoid chimeras
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.
Time frame: Day 84 post-transplant
Incidence of infections
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.
Time frame: Assessed up to 5 years
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.