RATIONALE: Giving low doses of chemotherapy, such as melphalan and fludarabine, and a monoclonal antibody, such as alemtuzumab, before a donor bone marrow or peripheral blood stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine after the transplant may stop this from happening. PURPOSE: This phase II trial is studying how well fludarabine, melphalan, alemtuzumab, and peripheral stem cell transplant work in treating patients with hematologic cancer.
OBJECTIVES: Overall survival-12 months Overall survival-24 months Acute Graft-versus-Host Disease Matched Related patients-up to 4 months post transplant Acute Graft-versus-Host Disease Unrelated and Mismatched related patients- up to 4 months post transplant Chronic Graft-versus-Host Disease Matched Related patients- up to 2 years post transplant Chronic Graft-versus-host disease Unrelated and Mismatched related patients- up to 2 years post transplant * OUTLINE: Patients are stratified according to donor type (HLA-matched related vs HLA-matched unrelated, single HLA-allele disparate related, or unmatched) (HLA-mismatched related or matched unrelated donor stratum closed to accrual as of 1/11/06). Patients receive a nonmyeloablative regimen comprising alemtuzumab IV over 8 hours on days -8 to -5, fludarabine IV over 30 minutes on days -8 to -4, and melphalan IV over 30 minutes on days -3 and -2. Allogeneic peripheral blood stem cells or bone marrow is infused on day 0. Patients receive graft-versus host disease prophylaxis comprising cyclosporine IV every 12 hours beginning on day -1 and continuing orally as tolerated until day 100. Patients are followed every 6 weeks for 6 months, every 3 months for 6 months, every 3-6 months for 1 year, and then annually thereafter or as clinically indicated. PROJECTED ACCRUAL: A maximum of 50 patients (25 HLA-matched related and 25 HLA-mismatched related or matched unrelated) will be accrued for this study within 2 years (HLA-mismatched related or matched unrelated donor stratum closed to accrual as of 1/11/06).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
51
Consenting individuals will receive pretransplant immunosuppressive cytoreduction, which will consist of 4 days of Campath-1H, 5 days of fludarabine, and two days of melphalan. All therapy should be completed approximately 24-36 hours before administration of the primary allograft. Campath-1H (20mg/dose/day) will be administered for each of four days from day -8 to day -5, inclusive. Each dose will be infused intravenously over 8 hours.
Patients will be treated with Cyclosporine as prophylaxis against GvHD. Cyclosporine will be initiated at least 1 day prior to transplant at a dose of 1.5 mg / kg IV q12h (3 mg / kg / day = total daily dose). Dose will thereafter be adjusted to maintain a trough serum level of 200-300 ng /ml. Cyclosporine will be administered intravenously until the patient tolerates full alimentation, at which time conversion to oral dosing to sustain therapeutic levels will be initiated according to standard BMT service guidelines.
Fludarabine, 25mg/m2/d will be administered for each of five days from day -8 to day -4, inclusive. Each dose will be infused intravenously over 30 minutes.
Melphalan will be administered intravenously over 30 minutes on each of two days from day -3 to day -2, inclusive. The dose for recipients of HLA-matched related grafts will be 50 mg/m2/day x 2. The dose for recipients of HLA-matched unrelated and HLA-single allele disparate related or unrelated marrow or PBSC transplants will be 70 mg/m2/day x 2.
Memorial Sloan-Kettering Cancer Center
New York, New York, United States
Overall Survival
Time frame: 12 months post transplant
Overall Survival
Time frame: 24 months post transplant
Acute Graft-versus-Host Disease Matched Related Patients
Grade III-IV Acute Graft-versus-Host Disease
Time frame: up to 4 months post transplant
Acute Graft-versus-Host Disease Unrelated and Mismatched Related Patients
Grade III-IV Acute Graft-versus-Host Disease
Time frame: up to 4 months post transplant
Extensive Chronic Graft-versus-Host Disease Matched Related Patients
Time frame: up to 2 years post transplant
Extensive Chronic Graft-versus-Host Disease Unrelated and Mismatched Related Patients
Time frame: up to 2 years post transplant
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.