Combination Chemotherapy, Tacrolimus, and Mycophenolate Mofetil in Treating Patients Who Are Undergoing a Donor Bone Marrow Transplant For Hematologic Cancer
RATIONALE: Giving chemotherapy before a donor bone marrow transplant helps stop the growth of cancer and abnormal cells and helps 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 cyclophosphamide, mycophenolate mofetil, or tacrolimus after transplant may stop this from happening.
PURPOSE: This clinical trial is studying how well giving combination chemotherapy together with tacrolimus and mycophenolate mofetil works in treating patients who are undergoing a donor bone marrow transplant for hematologic cancer.
|Chronic Myeloproliferative Disorders Leukemia Lymphoma Multiple Myeloma and Plasma Cell Neoplasm Myelodysplastic Syndromes||Drug: busulfan Drug: cyclophosphamide Drug: mycophenolate mofetil Drug: tacrolimus Procedure: allogeneic bone marrow transplantation Procedure: bone marrow ablation with stem cell support||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||HLA Matched Related and Unrelated Bone Marrow Transplantation With Busulfan/Cyclophosphamide and Post Transplantation Cyclophosphamide for Hematological Malignancies|
- Dose Finding [ Time Frame: Day 100 ]
To find the optimal dose of post-grafting immunosuppression with high-dose cyclophosphamide (Cy), FK-506 and MMF following myeloablative fully HLA-matched related or unrelated BMT for the patients with hematological malignancies who are at high risk of relapse.
To estimate the incidence and severity of acute GVHD and other toxicities following myeloablative fully HLA-matched related or unrelated BMT using this approach for the patients with hematological malignancies
- Immune reconstitution and disease control [ Time Frame: Survival ]
To evaluate immune reconstitution following HLA-matched related or unrelated myeloablative BMT and post-grafting immunosuppression with high dose Cy, FK-506 and MMF.
To evaluate disease control after myeloablative fully HLA-matched related or unrelated BMT for the patients with hematological malignancies who are at high risk of relapse when Cy is included in the post-grafting immune suppression
|Study Start Date:||May 2004|
|Estimated Primary Completion Date:||April 2017 (Final data collection date for primary outcome measure)|
- Determine the optimal dose of post-transplant immunosuppression comprising high-dose cyclophosphamide, tacrolimus, and mycophenolate mofetil administered after myeloablative conditioning chemotherapy comprising busulfan and cyclophosphamide followed by allogeneic bone marrow transplantation in patients with high-risk hematologic malignancies.
- Determine the incidence and severity of acute graft-versus-host disease in patients treated with this regimen.
- Determine other toxic effects of this regimen in these patients.
- Determine immune reconstitution in patients treated with this regimen.
- Determine disease control in patients treated with this regimen.
OUTLINE: This is a pilot study. Patients are stratified according to age (≤ 19 years old vs > 19 years old).
- Myeloablative conditioning chemotherapy: Patients receive busulfan IV or orally 4 times daily on days -7 to -4 OR days -6 to -3 and cyclophosphamide IV over 1 hour once daily on days -3 to -1 OR days -2 and -1.
- Allogeneic bone marrow transplantation: Patients undergo allogeneic bone marrow transplantation on day 0.
Immunosuppression therapy: Patients receive 1 of the following immunosuppressive treatment regimens:
- Regimen 1: Patients receive high-dose cyclophosphamide IV over 1 hour on day 3.
- Regimen 2: Patients receive high-dose cyclophosphamide IV over 1 hour on days 3 and 4.
- Regimen 3: Patients receive high-dose cyclophosphamide as in regimen 2 and oral mycophenolate mofetil three times daily on days 5-35.
- Regimen 4: Patients receive high-dose cyclophosphamide as in regimen 2 and mycophenolate mofetil as in regimen 3. Patients also receive tacrolimus IV or orally twice daily on days 5-50.
After completion of study transplantation, patients are followed at 30 and 60 days, 6 months, 1 year, and then annually thereafter.
PROJECTED ACCRUAL: Approximately 30-60 patients (approximately 5 per immunosuppressive treatment regimen) will be accrued for this study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00134017
|United States, Maryland|
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins|
|Baltimore, Maryland, United States, 21231-2410|
|Principal Investigator:||Leo Luznik, MD||Sidney Kimmel Comprehensive Cancer Center|