Alemtuzumab Plus Fludarabine and Melphalan With or Without Cyclosporine, Mycophenolate Mofetil, and Low-Dose Total-Body Irradiation Therapy Followed by Donor Peripheral Stem Cell Transplant in Treating Patients With Hematologic Cancer
RATIONALE: Giving low doses of chemotherapy, monoclonal antibodies, and radiation therapy before a donor 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 when they do not exactly match the patient's blood. 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 and mycophenolate mofetil before transplant may stop this from happening.
PURPOSE: This phase I/II trial is studying the side effects of alemtuzumab, fludarabine, and melphalan with or without cyclosporine, mycophenolate mofetil, and total-body irradiation before donor peripheral blood stem cell transplant and to see how well they work in treating patients with relapsed or refractory hematologic cancer.
Multiple Myeloma and Plasma Cell Neoplasm
Biological: therapeutic allogeneic lymphocytes
Drug: fludarabine phosphate
Drug: mycophenolate mofetil
Procedure: peripheral blood stem cell transplantation
Radiation: radiation therapy
|Study Design:||Primary Purpose: Treatment|
|Official Title:||A Trial of Reduced Intensity Conditioning and Transplantation of Haplotype Mismatched and KIR Class I Epitope-Mismatched Highly Purified CD34 Cells|
- Engraftment rate [ Designated as safety issue: No ]
- Risk of graft-vs-host disease [ Designated as safety issue: No ]
- Progression-free survival (PFS) [ Designated as safety issue: No ]
- Correlation of outcomes, engraftment, and PFS with number of detectable alloreactive natural killer cell clones [ Designated as safety issue: No ]
- Performance assessment [ Designated as safety issue: No ]
|Study Start Date:||May 2006|
- Determine the ability of a reduced-intensity conditioning regimen comprising alemtuzumab, fludarabine, and melphalan with or without cyclosporine, mycophenolate mofetil, and low-dose total body radiotherapy followed by haplotype-mismatched, KIR class I epitope-mismatched CD34-positive allogeneic peripheral blood stem cell transplantation to facilitate engraftment by day 35 post-transplantation in at least 85% of patients with relapsed, refractory, or poor-risk hematological malignancies.
- Determine the risk of graft-versus-host-disease in patients treated with these regimens.
- Determine, preliminarily, the efficacy of these regimens, in terms of progression-free survival, in these patients.
- Correlate outcomes, engraftment, and progression-free survival with the number of detectable alloreactive natural killer cell clones before transplantation and after engraftment in patients treated with these regimens.
- Determine immune reconstitution in patients treated with these regimens.
OUTLINE: This is a multicenter, pilot study. Patients are initially treated with conditioning regimen A. If adequate donor engraftment is not achieved, subsequent patients are treated with conditioning regimen B.
- Conditioning regimen A: Patients receive alemtuzumab IV over 2 hours on days -14 to -12; fludarabine IV over 30 minutes on days -7 to -3; and melphalan IV over 20-30 minutes on day -2.
- Conditioning regimen B: Patients receive oral or IV cyclosporine twice daily and oral or IV mycophenolate mofetil twice daily on days -15 to 0. Patients also receive alemtuzumab, fludarabine, and melphalan as in conditioning regimen A. Patients undergo low-dose total body irradiation twice daily on days -2 and -1.
All patients undergo allogeneic, T-cell-depleted, CD34-positive peripheral blood stem cell transplantation on day 0. Patients receive sargramostim (GM-CSF) subcutaneously beginning on day 1 and continuing until blood counts recover.
Patients are followed every 3 months for 1 year and then every 6 months for 5 years.
PROJECTED ACCRUAL: A total of 14-56 patients (14-28 per regimen) will be accrued for this study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00085449
Show 24 Study Locations
|Study Chair:||Sherif S. Farag, MD, PhD||Indiana University Melvin and Bren Simon Cancer Center|
|Investigator:||Koen Van Besien, MD||University of Chicago|