Total-Body Irradiation Followed By Cyclosporine and Mycophenolate Mofetil in Treating Patients With Severe Combined Immunodeficiency Undergoing Donor Bone Marrow Transplant

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Brief Title

Total-Body Irradiation Followed By Cyclosporine and Mycophenolate Mofetil in Treating Patients With Severe Combined Immunodeficiency Undergoing Donor Bone Marrow Transplant

Official Title

Induction of Mixed Hematopoietic Chimerism in Patients With Severe Combined Immunodeficiency Disorders Using Allogeneic Bone Marrow and Post-Transplant Immunosuppression With Cyclosporine and Mycophenolate Mofetil

Brief Summary

      This pilot clinical trial studies total-body irradiation followed by cyclosporine and
      mycophenolate mofetil in treating patients with severe combined immunodeficiency (SCID)
      undergoing donor bone marrow transplant. Giving total-body irradiation (TBI) before a donor
      bone marrow transplant using stem cells that closely match the patient's stem cells, helps
      stop the growth of abnormal cells. It may also stop the patient's immune system from
      rejecting the donor's stem cells. The donated stem cells may mix with the patient's immune
      cells and help destroy any remaining abnormal cells. Sometimes the transplanted cells from a
      donor can also make an immune response against the body's normal cells. Giving cyclosporine
      and mycophenolate mofetil after the transplant may stop this from happening.
    

Detailed Description

      PRIMARY OBJECTIVES:

      I. To safely establish partial lymphoid chimerism (1-95% donor cluster of differentiation
      [CD]3+ cells) using a non-lethal conditioning regimen in patients with severe combined
      immunodeficiency syndrome.

      II. To define the kinetics of immune reconstitution following a non-lethal conditioning
      regimen in patients with immunodeficiency diseases.

      OUTLINE:

      Patients receive cyclosporine orally (PO) or intravenously (IV) on days -3 to 100 followed by
      a taper until day 180 and mycophenolate mofetil PO or IV on days 0-40 with a taper until day
      96 in the absence of unacceptable toxicity. Unrelated donor recipients also undergo TBI on
      day 0. Patients undergo bone marrow transplant on day 0.

      After completion of study treatment, patients are followed up at 6 months and then yearly for
      5 years.
    

Study Phase

Phase 1

Study Type

Interventional


Primary Outcome

Mixed hematopoietic chimerism in a population of pediatric patients with immunodeficiency diseases


Condition

Adenosine Deaminase Deficiency

Intervention

Allogeneic Bone Marrow Transplantation

Study Arms / Comparison Groups

 Treatment (cyclosporine, mycophenolate mofetil, transplant)
Description:  Patients receive cyclosporine PO or IV on days -3 to 100 followed by a taper until day 180 and mycophenolate mofetil PO or IV on days 0-40 with a taper until day 96 in the absence of unacceptable toxicity. Unrelated donor recipients also undergo TBI on day 0. Patients undergo bone marrow transplant on day 0.

Publications

* 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

Procedure

Estimated Enrollment

6

Start Date

August 11, 1997

Completion Date

December 26, 2018

Primary Completion Date

October 25, 2011

Eligibility Criteria

        Inclusion Criteria:

          -  Patients with severe combined immunodeficiency syndrome:

               -  SCID with presence of B lymphocytes

                    -  X-linked SCID (presence of B lymphocytes)

                    -  Autosomal recessive SCID

          -  Patients with severe combined immunodeficiency syndrome:

               -  SCID with absence of T and B lymphocytes

          -  Patients with severe combined immunodeficiency syndrome:

               -  Purine metabolite deficiencies, deficiencies of the purine metabolites

                    -  Adenosine deaminase (ADA) deficiency

                    -  Purine nucleoside phosphorylase (PNP) deficiency

          -  DONOR: Related donor who is human leukocyte antigen (HLA) genotypically identical at
             least at one haplotype and may be genotypically or phenotypically identical for
             serological typing for HLA-A, B, C, and at the allele level for DRB1 and DQB1; related
             donors other than siblings must be matched at HLA-A, B, and C (at highest resolution
             available at the time of donor selection) and at DRB1 and DQB1 by deoxyribonucleic
             acid (DNA) typing; if more than one HLA-identical sibling is available, priority will
             be given to the oldest normal donor

          -  DONOR: Unrelated donors who are prospectively matched for HLA-A, B, C, DRB1 and DQB1
             by DNA typing at the highest resolution routinely available at the time of donor
             selection; only a single allele disparity will be allowed for HLA-A, B, or C as
             defined by high resolution typing

        Exclusion Criteria:

          -  Patients with viral associated T cell immunodeficiency disorders, such as human
             immunodeficiency virus (HIV)

          -  Patients with other disease or organ dysfunction that would limit survival to less
             than 30 days

          -  DONOR: Identical twin

          -  DONOR: Pregnancy

          -  DONOR: HIV seropositive

          -  DONOR: A positive anti-donor cytotoxic cross match is absolute donor exclusion

          -  DONOR: Patient and donor pairs homozygous at a mismatched allele in the graft
             rejection vector are considered a two-HLA allele mismatch, i.e., the patient is
             A*0201, and this type of mismatch is not allowed

          -  DONOR: < 6 months old, > 75 years old
      

Gender

All

Ages

N/A - N/A

Accepts Healthy Volunteers

No

Contacts

Lauri Burroughs, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT00008450

Organization ID

1227.00

Secondary IDs

NCI-2010-02045

Responsible Party

Sponsor

Study Sponsor

Fred Hutchinson Cancer Research Center

Collaborators

 National Cancer Institute (NCI)

Study Sponsor

Lauri Burroughs, Principal Investigator, Fred Hutch/University of Washington Cancer Consortium


Verification Date

July 2019