Overview

This trial is active, not recruiting.

Conditions immune system disorder, severe combined immunodeficiency
Treatments cyclosporine, mycophenolate mofetil, total-body irradiation, allogeneic bone marrow transplantation, nonmyeloablative allogeneic hematopoietic stem cell transplantation, laboratory biomarker analysis
Phase phase 1
Sponsor Fred Hutchinson Cancer Research Center
Collaborator National Heart, Lung, and Blood Institute (NHLBI)
Start date August 1997
End date October 2011
Trial size 6 participants
Trial identifier NCT00008450, 1227.00, NCI-2010-02045, P01HL036444, P30CA015704

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification pharmacokinetics study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
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.
cyclosporine ciclosporin
Given PO or IV
mycophenolate mofetil Cellcept
Given PO or IV
total-body irradiation TBI
Undergo TBI
allogeneic bone marrow transplantation bone marrow therapy, allogeneic
Undergo allogeneic bone marrow transplant
nonmyeloablative allogeneic hematopoietic stem cell transplantation
Undergo nonmyeloablative allogeneic hematopoietic stem cell transplant
laboratory biomarker analysis
Correlative studies

Primary Outcomes

Measure
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
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

Eligibility Criteria

Male or female participants of any age.

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

Additional Information

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
Principal investigator Lauri Burroughs
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.
Trial information was received from ClinicalTrials.gov and was last updated in July 2016.
Information provided to ClinicalTrials.gov by Fred Hutchinson Cancer Research Center.