NCT00003145

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

Induction of Mixed Hematopoietic Chimerism Using Fludarabine, Low Dose TBI , PBSC Infusion and Post-Transplant Immunosuppression With Cyclosporine and Mycophenolate Mofetil to be Followed by Donor Lymphocyte Infusion In Patients With Chronic Myeloid Leukemia in Chronic and Accelerated Phases: A Multi-center Study

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 18 (actual)
• Sponsor: Fred Hutchinson Cancer Center · Academic / Other
• Sex: All
• Age: 74 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Accelerated Phase of Disease
• Childhood Chronic Myelogenous Leukemia, BCR-ABL1 Positive
• Chronic Myelogenous Leukemia, BCR-ABL1 Positive
• Chronic Phase of Disease
• Recurrent Disease

Interventions

Type	Name	Description
DRUG	Fludarabine Phosphate	Given IV
RADIATION	Total-Body Irradiation	Undergo TBI
PROCEDURE	Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation	Undergo allogeneic PBSCT
PROCEDURE	Peripheral Blood Stem Cell Transplantation	Undergo allogeneic PBSCT
DRUG	Cyclosporine	Given PO or IV
DRUG	Mycophenolate Mofetil	Given PO or IV
BIOLOGICAL	Therapeutic Allogeneic Lymphocytes	Given IV
OTHER	Laboratory Biomarker Analysis	Correlative studies

Timeline

• Start date: 1997-08-01
• Primary completion: 2005-03-01
• First posted: 2003-01-27
• Last updated: 2020-01-10

Locations

8 sites across 3 countries: United States, Germany, Italy