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

Brief Title

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

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

Brief Summary

      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

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

        -  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.

Study Phase

Phase 1

Study Type


Primary Outcome

Engraftment at 4 weeks post bone marrow transplantation through 100 days

Secondary Outcome

 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


Congenital Amegakaryocytic Thrombocytopenia


anti-thymocyte globulin

Study Arms / Comparison Groups

 Single arm of transplant
Description:  Receiving haplocompatible T cell depleted peripheral blood stem cell transplant


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status


Estimated Enrollment


Start Date

April 2005

Completion Date

December 2011

Primary Completion Date

December 2011

Eligibility 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




1 Year - 17 Years

Accepts Healthy Volunteers



Morton J. Cowan, MD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations



Organization ID


Secondary IDs


Responsible Party

Principal Investigator

Study Sponsor

University of California, San Francisco


 National Cancer Institute (NCI)

Study Sponsor

Morton J. Cowan, MD, Study Chair, University of California, San Francisco

Verification Date

November 2012