Study Stopped
Screenings yielded inadequate eligible subjects to enroll.
Donor Stem Cell Transplant, Pentostatin, and Total-Body Irradiation in Treating Patients With Hematological Cancer
T Cell-Reduced Unrelated Donor Allogeneic Peripheral Blood Stem Cell Transplantation With Pentostatin and Low-Dose Total Body Irradiation
2 other identifiers
interventional
N/A
0 countries
N/A
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
Started Sep 2008
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Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
September 1, 2008
CompletedFirst Submitted
Initial submission to the registry
December 31, 2008
CompletedFirst Posted
Study publicly available on registry
January 1, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 1, 2010
CompletedStudy Completion
Last participant's last visit for all outcomes
February 1, 2010
CompletedAugust 14, 2023
August 1, 2023
1.4 years
December 31, 2008
August 10, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Severe transplant-related toxicity
Severe transplant-related toxicity (grade III-IV adverse events) as assessed by NCI CTCAE v2.0
before day 100
Stable donor engraftment
Stable donor engraftment
by day 70
Mortality
Death
at day 100
Secondary Outcomes (1)
Incidence of grade III-IV acute graft-versus-host disease
at day 100
Study Arms (1)
Donor Stem Cell Transplant, Pentostatin & Total-Body Irradiation for Hematological Cancer
EXPERIMENTALThis 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.
Interventions
2 mg/kg IV over 2 hours every 12 hours starting at 0700 on days -1, 0, and +1 (total of six doses).
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.
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).
At days +28 and +70 post-transplant, patients' blood will be evaluated for CD3 and overall WBC chimerism.
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.
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.
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
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
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
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).
Each patient will receive up to four IV infusions administered over 30 minutes of donor T cells at increasing cell doses given at intervals.
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.
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.
Eligibility Criteria
You may qualify if:
- Acute myeloid leukemia (AML) meeting any of the following criteria:
- Antecedent hematologic disorder Therapy related Primary induction failure
- In first complete remission (CR1) with poor-risk cytogenetics, as defined by the following:
- del(5q)/-5 del(7q)/-7 abn(3q) t(6;9) del(20q) del(17p)
- +13 Complex karyotype t(9;22) = 11q23 rearrangement In second complete remission (CR2) or greater
- Acute lymphoblastic leukemia meeting any of the following criteria:
- In CR1 with WBC \> 50,000/mm³ at diagnosis
- In CR1 with poor-risk cytogenetics (i.e., t\[9;22\], t\[1;19\], t\[4;11\]) AND meets at least 1 of the following criteria:
- years of age AND received prior high-dose chemotherapy, total-body irradiation (TBI), or a radiation dose that precludes administration of 12 Gy of TBI = 50-75 years of age = 19-75 years of age with hematopoietic stem cell transplantation (HSCT) comorbidity index ≥ 3 CNS or testicular involvement at diagnosis No CR within 4 weeks of initial treatment Primary induction failure In CR2 or greater
- Myelodysplastic syndromes meeting the following criteria:
- Intermediate-2 or high-risk category as determined by International Prognostic Scoring System Not considered a candidate for intensive or standard chemotherapy or HSCT
- Chronic myelogenous leukemia meeting any of the following criteria:
- First chronic phase AND \< 40 years of age First chronic phase AND no hematologic response after 3 months of imatinib mesylate therapy First chronic phase AND never achieved a complete cytogenetic response during imatinib mesylate therapy First chronic phase AND loss of previously documented response Accelerated phase Blast crisis phase Chronic myeloproliferative disorder (i.e., polycythemia vera, essential thrombocythemia, myelofibrosis) Bone marrow blasts \> 5% and/or other evidence of progression to acute leukemia Chronic myelomonocytic leukemia Severe aplastic anemia Failed prior antithymocyte globulin and cyclosporine immunosuppressive therapy
- Mantle cell lymphoma meeting any of the following criteria:
- In CR1 In first partial remission (PR1) In CR2 or greater In second PR (PR2) or greater
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Nebraskalead
- National Cancer Institute (NCI)collaborator
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Robert Bociek, MD
University of Nebraska
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 31, 2008
First Posted
January 1, 2009
Study Start
September 1, 2008
Primary Completion
February 1, 2010
Study Completion
February 1, 2010
Last Updated
August 14, 2023
Record last verified: 2023-08