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Stem Cell Enriched, T Cell Depleted Haplocompatible Peripheral Blood Transplantation for Children With Myelodysplastic Disease, Leukemia, Marrow Failure Syndromes, or Severe Immunodeficiency Diseases

Phase 1
1 Year
17 Years
Not Enrolling
Congenital Amegakaryocytic Thrombocytopenia, Leukemia, Myelodysplastic Syndromes, Severe Congenital Neutropenia

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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


- 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

- 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


- 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


- 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


- See Disease Characteristics

Type of Study:


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:


Principal Investigator

Morton J. Cowan, MD

Investigator Role:

Study Chair

Investigator Affiliation:

University of California, San Francisco


United States: Food and Drug Administration

Study ID:




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



Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel HillChapel Hill, North Carolina  27599-7570
UCSF Helen Diller Family Comprehensive Cancer CenterSan Francisco, California  94115