Clinical trial NCT00027560
Conditions: Leukemia Lymphoma Multiple Myeloma and Plasma Cell Neoplasm Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Neoplasms
Keywords: recurrent childhood acute lymphoblastic leukemia recurrent adult Hodgkin lymphoma refractory multiple myeloma stage II multiple myeloma stage III multiple myeloma recurrent childhood lymphoblastic lymphoma recurrent childhood acute myeloid leukemia recurrent adult acute myeloid leukemia recurrent adult acute lymphoblastic leukemia relapsing chronic myelogenous leukemia refractory chronic lymphocytic leukemia recurrent/refractory childhood Hodgkin lymphoma recurrent grade 1 follicular lymphoma recurrent grade 2 follicular lymphoma recurrent grade 3 follicular lymphoma recurrent adult diffuse small cleaved cell lymphoma recurrent adult diffuse mixed cell lymphoma recurrent adult diffuse large cell lymphoma recurrent adult immunoblastic large cell lymphoma recurrent adult lymphoblastic lymphoma recurrent adult Burkitt lymphoma previously treated myelodysplastic syndromes recurrent childhood small noncleaved cell lymphoma recurrent childhood large cell lymphoma recurrent mantle cell lymphoma Waldenström macroglobulinemia childhood chronic myelogenous leukemia atypical chronic myeloid leukemia, BCR-ABL1 negative myelodysplastic/myeloproliferative neoplasm, unclassifiable recurrent marginal zone lymphoma recurrent small lymphocytic lymphoma extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue nodal marginal zone B-cell lymphoma splenic marginal zone lymphoma adult acute myeloid leukemia with 11q23 (MLL) abnormalities childhood myelodysplastic syndromes
Sponsor: Memorial Sloan Kettering Cancer Center
Start date: 2001-07-01; Completion date: 2009-04-01
Enrollment: 51 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
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.

Detailed description:
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).

Arms: arm 1: This is a stratified single-armed phase II study designed to investigate the safety and efficacy of hematopoietic cell allografts administered after nonmyeloablative cytoreduction.
Interventions: intervention 1: alemtuzumab intervention 2: cyclosporine intervention 3: fludarabine phosphate intervention 4: melphalan intervention 5: allogeneic bone marrow transplantation intervention 6: peripheral blood stem cell transplantation
Intervention descriptions: intervention 1: 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. intervention 2: 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. intervention 3: 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. intervention 4: 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. intervention 5: None intervention 6: None

Protocol documents: