Stem Cell Enriched, T Cell Depleted Haplocompatible Peripheral Blood Transplantation for Children With Myelodysplastic Disease, Leukemia, Marrow Failure Syndromes, or Severe Immunodeficiency Diseases
1 Year
17 Years
Both
Congenital Amegakaryocytic Thrombocytopenia, Leukemia, Myelodysplastic Syndromes, Severe Congenital Neutropenia
Trial Information
Stem Cell Enriched, T Cell Depleted Haplocompatible Peripheral Blood Transplantation for Children With Myelodysplastic Disease, Leukemia, Marrow Failure Syndromes, or Severe Immunodeficiency Diseases
OBJECTIVES:
- 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.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- 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
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Engraftment at 4 weeks post bone marrow transplantation through 100 days
Outcome Time Frame:
100 days
Safety Issue:
No
Principal Investigator
Morton J. Cowan, MD
Investigator Role:
Study Chair
Investigator Affiliation:
University of California, San Francisco
Authority:
United States: Food and Drug Administration
Study ID:
CDR0000462168
NCT ID:
NCT00295971
Start Date:
April 2005
Completion Date:
December 2011
Related Keywords:
- Congenital Amegakaryocytic Thrombocytopenia
- Leukemia
- Myelodysplastic Syndromes
- Severe Congenital Neutropenia
- childhood acute lymphoblastic leukemia in remission
- childhood acute myeloid leukemia in remission
- de novo myelodysplastic syndromes
- previously treated myelodysplastic syndromes
- secondary myelodysplastic syndromes
- secondary acute myeloid leukemia
- juvenile myelomonocytic leukemia
- chronic phase chronic myelogenous leukemia
- refractory anemia with excess blasts in transformation
- refractory anemia with excess blasts
- severe congenital neutropenia
- congenital amegakaryocytic thrombocytopenia
- childhood chronic myelogenous leukemia
- childhood myelodysplastic syndromes
- Immunologic Deficiency Syndromes
- Leukemia
- Myelodysplastic Syndromes
- Preleukemia
- Neutropenia
- Thrombocytopenia
Name | Location |
|---|---|
| Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill | Chapel Hill, North Carolina 27599-7570 |
| UCSF Helen Diller Family Comprehensive Cancer Center | San Francisco, California 94115 |
