Fludarabine and Busulfan Followed by Donor Peripheral Stem Cell Transplant and Antithymocyte Globulin, Tacrolimus, and Methotrexate in Treating Patients With Myeloid Cancer
|ClinicalTrials.gov Identifier: NCT00346359|
Recruitment Status : Completed
First Posted : June 29, 2006
Last Update Posted : May 14, 2010
RATIONALE: Giving low doses of chemotherapy, such as fludarabine and busulfan, before a donor peripheral stem cell transplant helps stop the growth of abnormal and 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 abnormal or 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 antithymocyte globulin, tacrolimus, and methotrexate before or after transplant may stop this from happening.
PURPOSE: This phase II trial is studying how well giving fludarabine together with busulfan followed by donor peripheral stem cell transplant and antithymocyte globulin, tacrolimus, and methotrexate works in treating patients with myeloid cancer.
|Condition or disease||Intervention/treatment||Phase|
|Chronic Myeloproliferative Disorders Graft Versus Host Disease Leukemia Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Diseases||Biological: anti-thymocyte globulin Drug: busulfan Drug: fludarabine phosphate Drug: methotrexate Drug: tacrolimus Procedure: allogeneic hematopoietic stem cell transplantation Procedure: peripheral blood stem cell transplantation||Phase 2|
- Determine the incidence and severity of acute graft-versus-host disease (GVHD) in patients with myeloid malignancies treated with conditioning regimen comprising fludarabine phosphate and busulfan followed by allogeneic peripheral blood stem cell transplantation and GVHD prophylaxis comprising antithymocyte globulin, tacrolimus, and methotrexate.
- Determine the incidence of donor engraftment in patients treated with this regimen.
- Determine the pharmacokinetics of IV busulfan, including interdose variability and evaluation of a limited sampling strategy, in these patients.
- Determine the pharmacokinetics of antithymocyte globulin in these patients.
- Determine the pharmacokinetics of fludarabine phosphate and its effect on lymphocytes in these patients.
- Determine the incidence of specific toxic effects ≥ grade 3 in patients treated with this regimen.
- Determine the incidence and severity of chronic GVHD in these patients.
- Determine the incidence of nonrelapsing mortality at 100 days and at 1 year after transplantation in these patients.
- Determine the incidence of relapse in these patients.
- Determine relapse-free survival of these patients.
- Determine the incidence of Epstein-Barr virus activation in these patients.
- Conditioning regimen: Patients receive fludarabine phosphate IV over 30 minutes on days -6 to -2 and busulfan IV over 3 hours on days -5 to -2. Prior to the conditioning regimen, patients whose cerebrospinal fluid is positive for malignant cells receive intrathecal methotrexate or cranial irradiation for CNS prophylaxis.
- Allogeneic peripheral blood stem cell (PBSC) transplantation: Patients receive filgrastim (G-CSF)-mobilized allogeneic PBSCs IV on day 0.
- Graft-versus-host disease prophylaxis: Patients receive antithymocyte globulin IV over at least 10 hours on days -3 to -1. They also receive tacrolimus orally twice daily or IV continuously beginning on day -1 and continuing until up to day 55, followed by a taper until day 180 in the absence of graft-versus-host disease. Patients also receive methotrexate IV on days 1, 3, 6, and 11.
After completion of study treatment, patients are followed annually.
PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Masking:||None (Open Label)|
|Official Title:||Conditioning For Hematopoietic Cell Transplantation With Fludarabine Plus Targeted IV Busulfan and GVHD Prophylaxis With Thymoglobulin, Tacrolimus and Methotrexate in Patients With Myeloid Malignancies|
|Study Start Date :||March 2006|
|Actual Study Completion Date :||November 2007|
- Incidence and severity of acute graft-versus-host disease (GVHD)
- Incidence of donor engraftment
- Pharmacokinetics of IV busulfan including interdose variability and evaluation of a limited sampling strategy
- Pharmacokinetics of antithymocyte globulin
- Pharmacokinetics of fludarabine phosphate and its effect on lymphocytes
- Incidence of specific toxic effects ≥ grade 3
- Incidence and severity of chronic GVHD
- Incidence of nonrelapsing mortality at 100 days and at 1 year after transplantation
- Incidence of relapse
- Relapse-free survival
- Incidence of Epstein-Barr virus activation and post-transplantation lymphoproliferative disease
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00346359
|United States, Washington|
|Fred Hutchinson Cancer Research Center|
|Seattle, Washington, United States, 98109-1024|
|Study Chair:||Paul V. O'Donnell, MD, PhD||Fred Hutchinson Cancer Research Center|