Donor Stem Cell Transplant in Treating Young Patients With Myelodysplastic Syndrome, Leukemia, Bone Marrow Failure Syndrome, or Severe Immunodeficiency Disease
NCT ID: NCT00295971
Last Updated: 2012-11-12
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE1
21 participants
INTERVENTIONAL
2005-04-30
2011-12-31
Brief Summary
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PURPOSE: This phase I trial is studying the side effects and best dose of donor T cells and antithymocyte globulin when given together with chemotherapy and total-body irradiation in treating young patients who are undergoing T-cell depleted donor stem cell transplant for myelodysplastic syndrome, leukemia, bone marrow failure syndrome, or severe immunodeficiency disease.
Detailed Description
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* Determine the efficacy and toxicity of stem cell-enriched, T-cell-depleted, haplocompatible allogeneic hematopoietic stem cell transplantation in children with high-risk myelodysplastic syndromes, high-risk leukemia, severe acquired or congenital cytopenias, or primary immunodeficiency diseases.
* Determine the toxicity of a fludarabine and thiotepa-containing regimen in combination with lower doses of antithymocyte globulin in these patients.
* Determine the engraftment rate in patients treated with this regimen.
* Define T-cell reconstitution in these patients.
* Determine the toxicity and effects of administering stem cell and T-cell boosts after transplantation on hematopoiesis and immune reconstitution in these patients.
OUTLINE: This is a dose-escalation study of donor CD3+ cells and antithymocyte globulin (ATG).
* Cytoreductive regimen: Patients undergo total body irradiation twice daily on days -9 to -7. Patients also receive fludarabine IV on days -6 to -2, thiotepa IV every 12 hours on day -6, and ATG IV on days -5 to -2.
* Transplantation: Patients undergo CD34-enriched, T-cell-depleted, haplocompatible allogeneic peripheral blood stem cell or bone marrow transplantation on day 0.
* Donor T-cell infusion:Patients with no active graft-vs-host disease and evidence of engraftment but low absolute CD34+ lymphocyte count at 12 weeks post transplant may receive donor CD3+ cells at 4-week intervals.
* Donor stem cell boost: Patients with engraftment but either cytokine or transfusion dependent at 12 weeks post transplant may receive a boost of donor CD34+ cells.
Cohorts of 3-6 patients receive escalating doses of donor CD3+ cells and ATG until the optimum is determined. The optimum dose is defined as the dose at which both engraftment and T-cell recovery occur, without dose-limiting toxicity, in ≥ 5 of 6 patients.
After the completion of study treatment, patients are followed periodically for 5 years and then every 5 years thereafter.
PROJECTED ACCRUAL: A total of 21 patients will be accrued for this study.
Conditions
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Keywords
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Single arm of transplant
Receiving haplocompatible T cell depleted peripheral blood stem cell transplant
anti-thymocyte globulin
therapeutic allogeneic lymphocytes
fludarabine phosphate
thiotepa
allogeneic bone marrow transplantation
allogeneic hematopoietic stem cell transplantation
in vitro-treated peripheral blood stem cell transplantation
total-body irradiation
Interventions
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anti-thymocyte globulin
therapeutic allogeneic lymphocytes
fludarabine phosphate
thiotepa
allogeneic bone marrow transplantation
allogeneic hematopoietic stem cell transplantation
in vitro-treated peripheral blood stem cell transplantation
total-body irradiation
Eligibility Criteria
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Inclusion Criteria
* Diagnosis of one of the following:
* Acute lymphoblastic leukemia in ≥ 2nd remission or delayed remission induction
* High-risk myelodysplastic syndromes
* Refractory anemia with excess blasts (RAEB)
* RAEB in transformation
* Chronic myelogenous leukemia in second chronic phase
* No accelerated phase (\> 5% blasts in marrow)
* Juvenile myelomonocytic leukemia
* Acute nonlymphoblastic leukemia in \> 1st remission or induction failure and \< 30% blasts in marrow
* Severe aplastic anemia, defined as absolute neutrophil count \< 500/mm\^3 and platelet and/or red blood cell transfusion dependent
* Unresponsive to immunosuppressive therapy
* No Fanconi's anemia
* Congenital marrow aplasias unresponsive to cytokines and transfusion dependent
* Inherited immunodeficiency disease involving neutrophils or lymphocytes, including any of the following:
* Chediak-Higashi disease
* Wiskott-Aldrich syndrome
* Combined immunodeficiency disease (Nezelof's)
* Hyper IgM syndrome
* No relapsed disease
* Haplocompatible related donor, including parent, cousin, aunt, uncle, grandparent, half-sibling, or sibling (≥ 12 years of age), available
* 2 or 3 HLA antigen mismatch
* At least a 3 HLA antigen genotypic match
* No closely matched related or unrelated donor available in sufficient time to do the transplant
PATIENT CHARACTERISTICS:
* No active hepatitis or cytomegalovirus infection
* Cardiac ejection fraction ≥ 30%
* Creatinine clearance ≥ 70 mL/min
* DLCO ≥ 70% of predicted
* No active infection
* No HIV positivity
PRIOR CONCURRENT THERAPY:
* See Disease Characteristics
1 Year
17 Years
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
University of California, San Francisco
OTHER
Responsible Party
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Morton Cowan
Professor
Principal Investigators
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Morton J. Cowan, MD
Role: STUDY_CHAIR
University of California, San Francisco
Locations
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UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, United States
Countries
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Other Identifiers
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UCSF-01151
Identifier Type: -
Identifier Source: secondary_id
UCSF-H411-17122-07
Identifier Type: -
Identifier Source: secondary_id
CDR0000462168
Identifier Type: -
Identifier Source: org_study_id