This clinical trial studies fludarabine phosphate, low-dose total-body irradiation, and peripheral blood stem cell transplant followed by donor lymphocyte infusion in treating older patients with chronic myeloid leukemia. Giving chemotherapy and total-body irradiation before a donor bone marrow transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the 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. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil after the transplant may stop this from happening. 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 (called graft-versus-tumor effect). Giving an infusion of the donor's white blood cells (donor lymphocyte infusion) may boost this effect.
PRIMARY OBJECTIVES: I. To determine if mixed hematopoietic chimerism can be safely established using a non-myeloablative conditioning regimen in patients \> 65 years of age with chronic myeloid leukemia (CML) in chronic or accelerated phase who have human leukocyte antigen (HLA) identical related donors. II. To determine if mixed chimerism, established with non-myeloablative conditioning regimens, can be converted to full donor hematopoietic chimerism by infusions of donor lymphocytes (DLI), and thereby produce an immunologic cure of the malignancy. OUTLINE: CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) on days -4 to -2 and undergo low-dose total-body irradiation (TBI) on day 0. TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation (PBSCT) on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine orally (PO) twice daily (BID) or IV BID or thrice daily (TID) on days -3 to 56 with taper to day 77 or 180, and mycophenolate mofetil PO or IV BID on days 0-27. DLI: At least 2 weeks after completion of immunosuppression, patients with \> 5% donor cluster of differentiation (CD)3+ T cells and no evidence of graft-versus-host disease (GVHD) receive donor lymphocytes IV over 30 minutes. Patients may receive up to 3 DLIs at increasing cell doses in the absence of GVHD. After completion of study treatment, patients are followed up periodically for 5 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
18
Given IV
Undergo TBI
Undergo allogeneic PBSCT
Undergo allogeneic PBSCT
Given PO or IV
Given PO or IV
Given IV
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
VA Puget Sound Health Care System
Seattle, Washington, 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
Safety of establishing mixed chimerism using this non-lethal conditioning regimen, in terms of development of GVHD, myelosuppression, infections, and treatment-related mortality
All unexpected toxicities will be summarized and reported.
Time frame: Within the first 65 days
Proportion of patients who successfully establish mixed chimerism (evidence of donor engraftment) and the proportion who convert to full donor chimeras among those who were mixed
Estimated and corresponding confidence intervals presented. Mixed chimerism is detection of donor T cells (CD3+) and granulocytes (CD33+), as proportion of total T cell and granulocyte population of \> 5% and \< 95% in peripheral blood. Full donor chimerism is \> 95% donor CD3+ T cells. Increasing donor chimerism is absolute increase of 20% of CD3+ T cells over chimerism evaluation of previous month. Decreasing donor chimerism is absolute decrease of 20% of CD3+ T cell chimerism over previous month. Low donor chimerism is \< 40% CD3+ T cells after HSCT.
Time frame: Day 28
Proportion of patients who successfully establish mixed chimerism (evidence of donor engraftment) and the proportion who convert to full donor chimeras among those who were mixed
Estimated and corresponding confidence intervals presented. Mixed chimerism is detection of donor T cells (CD3+) and granulocytes (CD33+), as proportion of total T cell and granulocyte population of \> 5% and \< 95% in peripheral blood. Full donor chimerism is \> 95% donor CD3+ T cells. Increasing donor chimerism is absolute increase of 20% of CD3+ T cells over chimerism evaluation of previous month. Decreasing donor chimerism is absolute decrease of 20% of CD3+ T cell chimerism over previous month. Low donor chimerism is \< 40% CD3+ T cells after HSCT.
Time frame: Day 56
Proportion of patients experiencing a complete antileukemic response
Reported in a descriptive manner and confidence intervals will be presented for all estimates.
Time frame: At 12 weeks after the final DLI
Proportion of patients experiencing GVHD
Reported in a descriptive manner and confidence intervals will be presented for all estimates.
Time frame: Until day 90 after the last DLI
Proportion of patients experiencing non-relapse mortality
Reported in a descriptive manner and confidence intervals will be presented for all estimates.
Time frame: Within 65 days of transplant
Incidence of myelosuppression after initial PBSC infusion
Defined as absolute neutrophil count \[ANC\] \< 500 for \> 2 days, platelets \< 20,000 for \> 2 days.
Time frame: Until 2 months post-transplant
Incidence of aplasia after DLI
Time frame: Until 2 months post-transplant
Incidence of grades 2-4 acute GVHD after DLI
Time frame: Until day 90 after the last DLI
Incidence of grades 2-4 acute GVHD after PBSC infusion
Time frame: Until day 90 after the last DLI
Incidence of grade chronic extensive GVHD after DLI
Time frame: At 1 year
Dose of CD3+ cells required to convert mixed to full lymphoid chimeras
Time frame: Day 56
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