Trial record 6 of 47 for:    "ZAP70-related severe combined immunodeficiency" OR "Severe Combined Immunodeficiency"

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:
Collaborators:
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT00008450
First received: January 6, 2001
Last updated: July 17, 2014
Last verified: July 2014
  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
Immune System Disorder
Severe Combined Immunodeficiency
Drug: cyclosporine
Drug: mycophenolate mofetil
Radiation: total-body irradiation
Procedure: allogeneic bone marrow transplantation
Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
Other: laboratory biomarker analysis

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: 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:
  • Extent of chimerism in specific subpopulations by assessing T (CD3+3), B (CD19/20+), NK (CD56+), and myeloid (CD33+/13+) of bone marrow aspirate and peripheral blood [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Extent of immune deficiency and tempo of immune reconstitution of lymphoid subsets T (CD4+, CD8+, CD3+), B (CD19+, CD20+), and NK (CD56+) as assessed by flow cytometry [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]

Enrollment: 6
Study Start Date: August 1997
Primary Completion Date: October 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.
Drug: cyclosporine
Given PO or IV
Other Names:
  • ciclosporin
  • cyclosporin
  • cyclosporin A
  • CYSP
  • Sandimmune
Drug: mycophenolate mofetil
Given PO or IV
Other Names:
  • Cellcept
  • MMF
Radiation: total-body irradiation
Undergo TBI
Other Name: TBI
Procedure: allogeneic bone marrow transplantation
Undergo allogeneic bone marrow transplant
Other Names:
  • bone marrow therapy, allogeneic
  • bone marrow therapy, allogenic
  • transplantation, allogeneic bone marrow
  • transplantation, allogenic bone marrow
Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
Undergo nonmyeloablative allogeneic hematopoietic stem cell transplant
Other: laboratory biomarker analysis
Correlative studies

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

Genders Eligible for Study:   Both
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
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00008450

Locations
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Investigators
Principal Investigator: Lauri Burroughs Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT00008450     History of Changes
Other Study ID Numbers: 1227.00, NCI-2010-02045, 1227.00, P30CA015704, P01HL036444
Study First Received: January 6, 2001
Last Updated: July 17, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Severe Combined Immunodeficiency
Immunologic Deficiency Syndromes
Immune System Diseases
Infant, Newborn, Diseases
DNA Repair-Deficiency Disorders
Metabolic Diseases
Cyclosporins
Cyclosporine
Mycophenolate mofetil
Mycophenolic Acid
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Dermatologic Agents
Antirheumatic Agents
Antibiotics, Antineoplastic
Antineoplastic Agents

ClinicalTrials.gov processed this record on August 19, 2014