Donor Stem Cell Transplant, Pentostatin, and Total-Body Irradiation in Treating Patients With Hematological Cancer
RATIONALE: Giving low doses of chemotherapy and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells 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. Removing the T cells from the donor cells before transplant and giving cyclosporine and mycophenolate mofetil after transplant may stop this from happening.
PURPOSE: This phase I/II trial is studying the side effects of giving a donor stem cell transplant after pentostatin and total-body irradiation and to see how well it works in treating patients with hematological cancer.
|Chronic Myeloproliferative Disorders Leukemia Lymphoma Myelodysplastic Syndromes Nonmalignant Neoplasm||Drug: cyclosporine Drug: mycophenolate mofetil Drug: pentostatin Genetic: cytogenetic analysis Genetic: fluorescence in situ hybridization Genetic: protein analysis Other: flow cytometry Other: immunoenzyme technique Other: laboratory biomarker analysis Other: reduced-intensity transplant conditioning procedure Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation Procedure: peripheral blood stem cell transplantation (PBSC) Radiation: total-body irradiation||Phase 1 Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||T Cell-Reduced Unrelated Donor Allogeneic Peripheral Blood Stem Cell Transplantation With Pentostatin and Low-Dose Total Body Irradiation|
- Severe transplant-related toxicity (grade III-IV adverse events) as assessed by NCI CTCAE v2.0 [ Time Frame: before day 100 ]
- Stable donor engraftment [ Time Frame: by day 70 ]
- Mortality [ Time Frame: at day 100 ]
- Incidence of grade III-IV acute graft-versus-host disease [ Time Frame: at day 100 ]An interim analysis will be performed after the accrual of each five patients (i.e., three interim analyses and 1 final analysis) has reached day 100.
|Study Start Date:||September 2008|
|Study Completion Date:||February 2010|
|Primary Completion Date:||February 2010 (Final data collection date for primary outcome measure)|
Allopurinol 300 mg orally once daily x 10 days, to begin one day prior to treatment with Pentostatin (day -11 to day -2) .
Pentostatin 4 mg/m2/d IV over 30 minutes daily x 3 days, (days -10, -9, -8)to begin ten days prior to stem cell infusion (Day 0) .
Pre and Post Pentostatin Hydration: 1000ml Normal Saline IV over 2 hours pre each dose of Pentostatin and 1000ml Normal Saline IV over 4 hours post each dose of Pentostatin on days -10, -9, -8.
Pre Pentostatin Recommended Antiemetics: Ondansetron 32 mg IV over 30 minutes to be given 30 min. before each dose of Pentostatin on days -10, -9, -8. Alternative ondansetron equivalent or other ancillary antiemetics may be used at the discretion of the treating physician.
Pred Forte Eye Drops: two drops in each eye every 4 hours while awake x 7 days after starting Pentostatin (day -10 to day -4).
- To determine the safety of pentostatin and low-dose total body irradiation followed by T-cell-reduced unrelated donor peripheral blood stem cell transplantation, in terms of regimen-related toxicity, in patients with hematological malignancies.
- To evaluate the efficacy of this regimen, measured as engraftment rate and establishment of donor hematopoietic chimerism, in these patients.
- To determine the incidence of acute and chronic graft-versus-host disease in patients treated with this regimen.
- Reduced-intensity preparative regimen: Patients receive pentostatin IV over 30 minutes once daily on days -10 to -8 and undergo low-dose total-body irradiation on day -1.
- Unrelated donor peripheral blood stem cell transplantation (PBSCT): Patients undergo T-cell-reduced donor PBSCT on day 0.
- Graft-versus-host disease (GVHD) prophylaxis: Patients receive cyclosporine IV over 2 hours twice daily on days -1, 0, and 1 and then orally twice daily on days 2-70 followed by a taper in the absence of GVHD. Patients also receive oral mycophenolate mofetil twice daily on days 0-27 followed by a taper.
Patients undergo bone marrow aspirate and biopsies and blood sample collection periodically for laboratory studies. Samples are analyzed for cytokines (i.e., IL-6, TNF-γ, IL-1β, and IL-10) by ELISA; phenotypic, molecular, and functional analysis of immunologic reconstitution markers (i.e., PHA, IL-2, IL-4, IL-10, IL-12, Fas, FasL, TNF, TGF-β, and IFN-γ) by flow cytometry; and cytogenetics by FISH.
After completion of study treatment, patients are followed periodically.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00816413
|United States, Nebraska|
|UNMC Eppley Cancer Center at the University of Nebraska Medical Center|
|Omaha, Nebraska, United States, 68198-6805|
|Principal Investigator:||Robert Bociek, MD||University of Nebraska|