Donor Stem Cell Transplant, Pentostatin, and Total-Body Irradiation in Treating Patients With Hematological Cancer
|ClinicalTrials.gov Identifier: NCT00816413|
Recruitment Status : Withdrawn (Screenings yielded inadequate eligible subjects to enroll.)
First Posted : January 1, 2009
Last Update Posted : January 24, 2018
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.
|Condition or disease||Intervention/treatment||Phase|
|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|
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||0 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||T Cell-Reduced Unrelated Donor Allogeneic Peripheral Blood Stem Cell Transplantation With Pentostatin and Low-Dose Total Body Irradiation|
|Study Start Date :||September 2008|
|Actual Primary Completion Date :||February 2010|
|Actual Study Completion Date :||February 2010|
- Drug: cyclosporine
2 mg/kg IV over 2 hours every 12 hours starting at 0700 on days -1, 0, and +1 (total of six doses).
- Drug: mycophenolate mofetil
15 mg/kg orally twice a day starting day 0 until day +27 then stopped without tapering in the absence of aGVHD then tapered over two months in the absence of aGVHD. Doses will be rounded to the nearest 250 mg.
- Drug: 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).
- Genetic: cytogenetic analysis
At days +28 and +70 post-transplant, patients' blood will be evaluated for CD3 and overall WBC chimerism.
- Genetic: fluorescence in situ hybridization
Mixed chimerism is defined as the detection of 95% or less donor T cells (CD3+), expressed as a proportion of the total T cell and WBC population as measured by DNA.
- Genetic: protein analysis
Blood samples will be at baseline(day -11 or before) , days -8 and -1, prior to transplant on day 0, then weekly (days +7, +14, +21 and +28) post-transplant through day +28. Five ml's of blood will be drawn at each collection through a central line using heparinized vaccutainers. Samples will be spun down at 1200 g and plasma aspirated and stored in -80 oC until analyzed for the ELISA Assays being done for research purposes in this protocol.
- Other: flow cytometry
Peripheral blood Peripheral blood flow cytometry for immunophenotyping including Th/c1 and Th/c2 subsets, mitogens (PHA, PWM), NK and LAK function studies, DCs, apoptosis assay of tumor cells, and lymphocyte subsets (CD4, CD8, CD19, CD56
- Other: immunoenzyme technique
Peripheral blood for immunophenotyping including Th/c1 and Th/c2 subsets, mitogens (PHA, PWM), NK and LAK function studies, DCs, apoptosis assay of tumor cells, and lymphocyte subsets (CD4, CD8, CD19, CD56
- Other: laboratory biomarker analysis
Donor mononuclear cells from the stem cell product (SCP) obtained with apheresis will be analyzed for surface markers, including CD3, CD4, CD8, CD19, CD14, CD56, TCR+CD8+ cells, Th/c1 and Th/c2, Fas and FasL, and DCs, as well as for apoptosis
- Other: reduced-intensity transplant conditioning procedure
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).
- Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
Each patient will receive up to four IV infusions administered over 30 minutes of donor T cells at increasing cell doses given at intervals.
- Procedure: peripheral blood stem cell transplantation (PBSC)
PBSC are infused intravenously either by infusion or IV push on day 0 through a secure intravenous access (i.e. the double-lumen central catheter place pre transplant) according to institutional guidelines.
- Radiation: total-body irradiation
2.0 GY will be administered on day -1. Total-body irradiation (TBI) will consist of 2.0 GY at 8-12cGy/min via 6MV photons delivered AP/PA fields, without lung blocks or via lateral fields with lucite compensator along the head and neck region. TLD (thermal luminescent dosimetry) will be used to verify dose uniformity. It is anticipated that TBI will be given on day -1; however, the timing of TBI administration may be altered by factors beyond the control of the Principal Investigator because of the delivery of unrelated donor stem cells.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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|