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

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00008450
First Posted: January 8, 2001
Last Update Posted: July 14, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
National Cancer Institute (NCI)
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center
  Purpose
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.

Condition Intervention Phase
Adenosine Deaminase Deficiency Autosomal Recessive Disorder Immune System Disorder Purine-Nucleoside Phosphorylase Deficiency Severe Combined Immunodeficiency Severe Combined Immunodeficiency With Absence of T and B Cells X-Linked Severe Combined Immunodeficiency Procedure: Allogeneic Bone Marrow Transplantation Drug: Cyclosporine Other: Laboratory Biomarker Analysis Drug: Mycophenolate Mofetil Procedure: Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation Radiation: Total-Body Irradiation Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • Mixed hematopoietic chimerism in a population of pediatric patients with immunodeficiency diseases [ Time Frame: Up to 5 years ]
    It will be established whether a non-lethal conditioning regimen can successfully induce mixed hematopoietic chimerism in a population of pediatric patients with immunodeficiency diseases, without adverse effects on mortality.


Enrollment: 6
Actual Study Start Date: August 11, 1997
Primary Completion Date: October 25, 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (cyclosporine, mycophenolate mofetil, transplant)
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.
Procedure: Allogeneic Bone Marrow Transplantation
Undergo allogeneic bone marrow transplant
Other Names:
  • Allo BMT
  • Allogeneic BMT
Drug: Cyclosporine
Given PO or IV
Other Names:
  • 27-400
  • Ciclosporin
  • CsA
  • Cyclosporin
  • Cyclosporin A
  • Gengraf
  • Neoral
  • OL 27-400
  • Sandimmun
  • Sandimmune
  • SangCya
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Mycophenolate Mofetil
Given PO or IV
Other Names:
  • Cellcept
  • MMF
Procedure: Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation
Undergo nonmyeloablative allogeneic hematopoietic stem cell transplant
Other Names:
  • Non-myeloablative allogeneic transplant
  • Nonmyeloablative Stem Cell Transplantation
  • NST
Radiation: Total-Body Irradiation
Undergo TBI
Other Names:
  • Total Body Irradiation
  • Whole-Body Irradiation

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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00008450


Locations
United States, Washington
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
National Cancer Institute (NCI)
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
Principal Investigator: Lauri Burroughs Fred Hutch/University of Washington Cancer Consortium
  More Information

Responsible Party: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT00008450     History of Changes
Other Study ID Numbers: 1227.00
NCI-2010-02045 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
1227.00 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
P01HL036444 ( U.S. NIH Grant/Contract )
P30CA015704 ( U.S. NIH Grant/Contract )
First Submitted: January 6, 2001
First Posted: January 8, 2001
Last Update Posted: July 14, 2017
Last Verified: July 2017

Additional relevant MeSH terms:
Severe Combined Immunodeficiency
Disease
Immunologic Deficiency Syndromes
X-Linked Combined Immunodeficiency Diseases
Agammaglobulinemia
Immune System Diseases
Purine-Pyrimidine Metabolism, Inborn Errors
Pathologic Processes
Infant, Newborn, Diseases
DNA Repair-Deficiency Disorders
Metabolic Diseases
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Blood Protein Disorders
Hematologic Diseases
Lymphoproliferative Disorders
Lymphatic Diseases
Metabolism, Inborn Errors
Cyclosporins
Cyclosporine
Mycophenolic Acid
Mycophenolate mofetil
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Dermatologic Agents