This pilot clinical trial studies low-dose total body irradiation and donor peripheral blood stem cell transplant followed by donor lymphocyte infusion in treatment patients with non-Hodgkin lymphoma, chronic lymphocytic leukemia, or multiple myeloma. Giving total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. When 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. Once the donated stem cells begin working, the patient's immune system may see the remaining cancer cells as not belonging in the patient's body and destroy them. Giving an infusion of the donor's white blood cells (donor lymphocyte infusion) may boost this effect.
PRIMARY OBJECTIVES: I. To determine whether mixed hematopoietic chimerism can be safely established using a non-myeloablative conditioning regimen in patients with non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL) and multiple myeloma. II. To determine whether mixed chimerism, established with non- myeloablative conditioning regimens, can be safely converted to full donor hematopoietic chimerism by infusions of donor lymphocytes (DLI). OUTLINE: CYTOREDUCTION: If necessary, patients with advanced malignancies undergo cytoreductive chemotherapy to reduce tumor size at discretion of primary physician and study investigators. CONDITIONING REGIMEN: Patients undergo low-dose total-body irradiation followed by allogeneic peripheral blood stem cell (PBSC) transplant on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine intravenously (IV) twice daily (BID) on days -1 to 0 and then orally (PO) BID on days 1-35 with taper to day 56. Patients also receive mycophenolate mofetil PO BID on days 0-27. POST-TRANSPLANT DLI: Patients with mixed chimerism on day 56 and no evidence of graft-vs-host disease (GVHD) undergo DLI over 30 minutes on day 65 and may receive up to 3 additional infusions in the absence of GVHD and disease progression or persistence. Patients who have not achieved mixed chimerism at day 56 undergo DLI if complete response is not obtained after a 2 month monitoring period. After completion of study treatment, patients are followed up at 4, 6, 12, 18, and 24 months and then annually thereafter.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
63
Undergo cytoreductive chemotherapy
Undergo TBI
Undergo allogeneic PBSC transplant
Given IV or PO
Given PO
Undergo allogeneic PBSC transplant
Undergo DLI
City of Hope Medical Center
Duarte, California, United States
Stanford University Hospitals and Clinics
Stanford, California, United States
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States
Universitaet Leipzig
Leipzig, Germany
University of Torino
Torino, Italy
Incidence of GVHD, myelosuppression, and infections
At the conclusion of the study, all unexpected toxicities will be summarized and reported.
Time frame: Up to 5 years
Greater than 10% incidence of treatment-related mortality (TRM) after PBSC infusion, defined as death without evidence of disease progression
Time frame: Within 65 days of transplant
Greater than 20% incidence of TRM after DLI, defined as death without evidence of disease progression
Time frame: Within 12 months of DLI
Proportion of patients who successfully achieve mixed chimerism
The proportion of patients who successfully establish mixed chimerism in each group (patients with NHL, CLL or multiple myeloma vs patients with other malignancies) will be estimated and corresponding confidence intervals will be presented.
Time frame: Up to 5 years
Proportion of patients with mixed chimerism who successfully achieve full donor chimerism
The proportion of patients with mixed chimerism who are successfully converted to full donor chimerism in each group (patients with NHL, CLL or multiple myeloma vs patients with other malignancies) will be estimated and corresponding confidence intervals will be presented.
Time frame: Up to 5 years
Response of malignancy to DLI
Examined separately in the two groups of patients, and reported in a descriptive manner with confidence intervals presented.
Time frame: Up to 5 years
Incidence of myelosuppression after initial PBSC transplant
Defined as (absolute neutrophil count \[ANC\] \< 500 for \> 2 days, platelets \< 20,000 for \> 2 days). Examined separately in the two groups of patients, and reported in a descriptive manner with confidence intervals presented.
Time frame: Up to day 56
Incidence of aplasia after DLI
Examined separately in the two groups of patients, and reported in a descriptive manner with confidence intervals presented.
Time frame: Up to day 90
Incidence of grades 2-4 acute GVHD after DLI
Examined separately in the two groups of patients, and reported in a descriptive manner with confidence intervals presented.
Time frame: Up to day 90 post-DLI
Incidence of grades 2-4 acute GVHD after PBSC infusion
Examined separately in the two groups of patients, and reported in a descriptive manner with confidence intervals presented.
Time frame: Up to day 56
Incidence of chronic extensive GVHD after DLI
Examined separately in the two groups of patients, and reported in a descriptive manner with confidence intervals presented.
Time frame: Up to 1 year post-DLI
Dose of cluster of differentiation (CD)3+ cells required to convert mixed to full lymphoid chimeras
Examined separately in the two groups of patients, and reported in a descriptive manner with confidence intervals presented.
Time frame: Up to 5 years
Incidence of non-relapse mortality
Examined separately in the two groups of patients, and reported in a descriptive manner with confidence intervals presented.
Time frame: Up to 5 years
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