Donor Stem Cell Transplant in Treating Young Patients With Myelodysplastic Syndrome, Leukemia, Bone Marrow Failure Syndrome, or Severe Immunodeficiency Disease

Donor Stem Cell Transplant in Treating Young Patients With Myelodysplastic Syndrome, Leukemia, Bone Marrow Failure Syndrome, or Severe Immunodeficiency Disease
The recruitment status of this study is unknown because the information has not been verified recently.
Verified on July 2009 by National Cancer Institute (NCI).   Recruitment status was  Recruiting

First Received on February 23, 2006.  
Last Updated on July 7, 2009  
History of Changes
Sponsor: University of California, San Francisco
Collaborator: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI) Identifier: NCT00295971

RATIONALE: Giving chemotherapy and total body irradiation before a donor bone marrow transplant or peripheral blood stem cell transplant helps stop the growth of cancer cells. It also helps stop the patient’s immune system from rejecting the donor’s stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient’s bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body’s normal cells. Giving antithymocyte globulin and removing the T cells from the donor cells before transplant may stop this from happening.

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.

Condition Intervention Phase
Congenital Amegakaryocytic Thrombocytopenia
Myelodysplastic Syndromes
Severe Congenital Neutropenia
Biological: anti-thymocyte globulin
Biological: therapeutic allogeneic lymphocytes
Drug: fludarabine phosphate
Drug: thiotepa
Procedure: allogeneic bone marrow transplantation
Procedure: allogeneic hematopoietic stem cell transplantation
Procedure: in vitro-treated peripheral blood stem cell transplantation
Radiation: total-body irradiation
Phase I

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: Stem Cell Enriched, T Cell Depleted Haplocompatible Peripheral Blood Transplantation for Children With Myelodysplastic Disease, Leukemia, Marrow Failure Syndromes, or Severe Immunodeficiency Diseases

Resource links provided by NLM:

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

  • Engraftment at 4 weeks post bone marrow transplantation through 100 days [ Designated as safety issue: No ]

Secondary Outcome Measures:

  • Survival assessed monthly for 6 months, every 3 months for 2 years, every 6 months for 1 year, and then yearly for 5 years post transplantation [ Designated as safety issue: No ]
  • Disease-free survival and infection assessed monthly for 6 months, every 3 months for 2 years, every 6 months for 1 year, and then yearly for 5 years post transplantation [ Designated as safety issue: No ]
  • Graft-versus-host disease assessed monthly for 6 months, every 3 months for 2 years, every 6 months for 1 year, and then yearly for 5 years post transplantation [ Designated as safety issue: No ]
  • CD4 count in blood < 100/mm³ at 12 weeks [ Designated as safety issue: No ]

Estimated Enrollment: 21
Study Start Date: April 2005

Detailed Description:


  • 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.


Ages Eligible for Study:   1 Year to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No


  • 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
  Contacts and Locations

Please refer to this study by its identifier: NCT00295971

United States, California
UCSF Helen Diller Family Comprehensive Cancer Center Recruiting
San Francisco, California, United States, 94115
Contact: Clinical Trials Office – UCSF Helen Diller Family Comprehensi     877-827-3222        
United States, North Carolina
Lineberger Comprehensive Cancer Center at University of North Carolina – Chapel Hill Recruiting
Chapel Hill, North Carolina, United States, 27599-7295
Contact: Clinical Trials Office – Lineberger Comprehensive Cancer Cente     877-668-0683; 919-966-4432        
Sponsors and Collaborators
University of California, San Francisco
Study Chair: Morton J. Cowan, MD University of California, San Francisco
  More Information

Additional Information:

No publications provided Identifier: NCT00295971    
History of Changes
Other Study ID Numbers: CDR0000462168, UCSF-01151, UCSF-H411-17122-07
Study First Received: February 23, 2006
Last Updated: July 7, 2009
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):

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

Additional relevant MeSH terms:

Immunologic Deficiency Syndromes
Myelodysplastic Syndromes
Immune System Diseases
Neoplasms by Histologic Type
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Leukocyte Disorders
Blood Platelet Disorders
Antilymphocyte Serum
Fludarabine monophosphate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses processed this record on December 02, 2011

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