Cyclophosphamide and/or Mycophenolate Mofetil With or Without Tacrolimus in Treating Patients Who Are Undergoing a Donor Bone Marrow or Peripheral Stem Cell Transplant for Hematologic Cancer
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|ClinicalTrials.gov Identifier: NCT00255710|
Recruitment Status : Completed
First Posted : November 21, 2005
Last Update Posted : March 17, 2010
RATIONALE: Giving low doses of chemotherapy, such as fludarabine, and radiation therapy before a donor bone marrow or 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 cyclophosphamide, mycophenolate mofetil, and tacrolimus after transplant may stop this from happening.
PURPOSE: This phase I trial is studying cyclophosphamide and/or mycophenolate mofetil with or without tacrolimus to see which is the best regimen in treating patients who are undergoing a donor bone marrow or stem cell transplant for hematologic cancer.
|Condition or disease||Intervention/treatment||Phase|
|Chronic Myeloproliferative Disorders Graft Versus Host Disease Leukemia Lymphoma Multiple Myeloma and Plasma Cell Neoplasm Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Diseases||Biological: filgrastim Drug: cyclophosphamide Drug: fludarabine phosphate Drug: mycophenolate mofetil Drug: tacrolimus Procedure: allogeneic bone marrow transplantation Procedure: peripheral blood stem cell transplantation Radiation: radiation therapy||Phase 1|
- Determine a minimal (short-duration) post-transplant immunosuppression regimen comprising cyclophosphamide and/or mycophenolate mofetil with or without tacrolimus that results in ≤ 20% incidence of grade II or higher acute graft-versus-host disease (GVHD) in patients with hematologic malignancies undergoing nonmyeloablative allogeneic bone marrow or peripheral blood stem cell transplantation from an HLA-identical related donor.
- Determine the post-transplant immunosuppression regimen that results in < 10% incidence of nonengraftment, defined as < 5% donor chimerism in peripheral blood at day 60, in these patients.
- Determine the incidence and severity of acute GVHD in patients treated with these regimens.
- Determine the frequency of mixed chimerism in patients treated with these regimens.
- Nonmyeloablative allogeneic bone marrow transplantation (BMT) or peripheral blood stem cell transplantation (PBSCT): Patients receive fludarabine IV on days -4 to -2 and undergo total-body irradiation on day -1. Patients undergo allogeneic BMT on day 0 or PBSCT on day 0 (and days 1 and 2, if needed). Patients receive filgrastim (G-CSF) beginning on day 5 and continuing until at least day 15 or until blood counts recover.
Sequentially increasing levels of post-transplant immunosuppression: Cohorts of patients are enrolled into 1 of the following regimens:
- Regimen 1 (post-BMT immunosuppression): Patients receive cyclophosphamide IV on day 3 only.
- Regimen 2 (post-BMT immunosuppression): Patients receive mycophenolate mofetil (MMF) once on day 3 and then twice daily on days 4-32.
- Regimen 3 (post-BMT immunosuppression): Patients receive cyclophosphamide IV on days 3 and 4 and MMF twice daily on days 4-33.
- Regimen 4 (post-PBSCT immunosuppression): Patients receive cyclophosphamide and MMF as in regimen 3.
- Regimen 5 (post-PBSCT immunosuppression): Patients receive cyclophosphamide and MMF as in regimen 3 and tacrolimus twice daily on days 4-33.
Cohorts of approximately 10-20 patients receive sequentially increasing levels of post-transplant immunosuppression until a minimal (short-duration) post-transplant immunosuppression regimen is identified. The minimal post-transplant immunosuppression regimen is defined as the regimen in which ≤ 3 of 10 or ≤ 6 of 20 patients develop grade II or higher acute graft-versus-host disease AND ≤ 2 of 10 or ≤ 4 of 20 patients fail to engraft 60 days post-transplantation. Once the minimal post-transplant immunosuppression regimen is identified, an additional 10 patients are treated with that regimen.
Patients are followed for 60 days after transplantation.
PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||60 participants|
|Masking:||None (Open Label)|
|Primary Purpose:||Supportive Care|
|Official Title:||Nonmyeloablative Bone Marrow Transplants in Hematologic Malignancies: Dose Finding Study for Post-Transplant Immunosuppression|
|Study Start Date :||July 2002|
- Post-transplant immunosuppression regimen with ≤ 20% incidence of a grade II-IV graft-versus-host-disease (GVHD) and < 10% incidence of nonengraftment (< 5% donor chimerism) at day 60 following transplant
- Incidence and severity of acute GVHD at day 60 following transplant
- Frequency of mixed chimerism defined as any detectable donor cells at day 60 following transplant
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00255710
|United States, Maryland|
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins|
|Baltimore, Maryland, United States, 21231-2410|
|Study Chair:||Carol A. Huff, MD||Sidney Kimmel Comprehensive Cancer Center|