IMM 0212: Busulfan With Fludarabine and Antithymocyte Globulin as Preparative Therapy for Hematopoietic Stem Cell Transplant for the Treatment of Severe Congenital T-Cell Immunodeficiency

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Brief Title

IMM 0212: Busulfan With Fludarabine and Antithymocyte Globulin as Preparative Therapy for Hematopoietic Stem Cell Transplant for the Treatment of Severe Congenital T-Cell Immunodeficiency

Official Title

Phase I/II Trial of De-Escalation of Busulfan With Fludarabine and Antithymocyte Globulin as Preparative Therapy for Hematopoietic Stem Cell Transplant for the Treatment of Severe Congenital T-Cell Immunodeficiency

Brief Summary

      This is a multi-institution, single arm, non-randomized pilot study coordinated by the
      Pediatric Blood and Marrow Transplant Consortium. Eligible patients will have severe combined
      immunodeficiency syndrome (SCID) or severe T-cell immunodeficiency disorder. Patients with
      these disorders do not have properly functioning immune systems. Without treatment, these
      disorders result in early childhood death. The standard treatment used for these diseases is
      to give the patient a stem cell transplant from a matched donor. The donor cells can be from
      a family member, an unrelated marrow donor or umbilical cord blood. The donor source will
      impact on transplant risks and approaches to the preparative regimen.

      There have been many different preparative regimens used for patients with SCIDS or severe
      T-cell immunodeficiency syndromes. Some patients have gotten no preparative regimen, while
      others have gotten only antithymocyte globulin (ATG; immune proteins made in horses that,
      when given, will kill lymphocytes). Still other patients have gotten conventional
      chemotherapy. In children treated with nothing or ATG alone, there is an increased risk of
      graft failure or only partial engraftment. When this happens, patients need life-long therapy
      with immunoglobulins to support the immune system. Children treated with chemotherapy
      generally have full immune recovery, but also may have major side effects from the
      chemotherapy. The side effects include infection, organ failure and infertility.

      This protocol, in combination with a parallel study with a separate preparative regimen, will
      attempt to answer the question of which patients with primary immunodeficiencies need a
      preparative regimen and what intensity is needed. Patients will be enrolled according to
      disease type and donor source. The purpose of this study is to see how much chemotherapy is
      actually needed for the transplant to work. To be able to do this and still make the
      transplant work, the drugs used to temporarily weaken the immune system will be strengthened.
      In groups, patients will be treated with lowering doses of the busulfan to find the lowest
      dose of this drug that is needed to get full immune recovery. The investigators hope this
      regimen will result in complete immune system recovery while limiting the side effects of
      chemotherapy. A second purpose of this study is to track the recovery of different parts of
      the immune system. The investigators also want to identify whether the recovery is coming
      from donor stem cells or from the patient.

      The patient will be admitted to the hospital to have the transplant and is expected to stay
      for up to 4 to 6 weeks. The preparative regimen will be made up of busulfan, fludarabine and
      antithymocyte globulin (ATG). After the preparative regimen, the cells from the donor will be
      given. To try and keep the patient's body from rejecting the donor cells and the donor cells
      from attacking the patient's body (graft-versus-host disease, or GVHD), cyclosporine will be

      The investigators will draw an extra 2 - 4 teaspoons of blood at specified time points to
      test for immune recovery and donor cell chimerism (the portion of the blood that belongs to
      the donor). Standard bone marrow transplant (BMT) clinical care will be provided with respect
      to pretransplant evaluation, peritransplant support, and posttransplant follow-up.

Study Phase

Phase 1/Phase 2

Study Type



T-Cell Immune Deficiency Diseases


Busulfan, Fludarabine and ATG


* 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


Completion Date

November 2006

Eligibility Criteria

        Inclusion Criteria:

          -  Patients with the following primary severe T-cell immune deficiency diseases and donor
             types will be eligible for this pilot trial:

               -  Immunophenotype: SCIDs with decreasing T, any B, increasing natural killer (NK)
                  with partial matched family member, unrelated donor marrow or cord blood, with or
                  without T depletion; OR

               -  Combined immunodeficiency disease (CID), including Wiskott-Aldrich and severe
                  DiGeorge's with any donor type.




N/A - N/A

Accepts Healthy Volunteers

Accepts Healthy Volunteers


Naynesh R Kamani, M.D., , 

Location Countries

United States

Location Countries

United States

Administrative Informations



Organization ID


Study Sponsor

Emory University

Study Sponsor

Naynesh R Kamani, M.D., Study Chair, George Washington University School of Medicine

Verification Date

September 2005