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

Severe Combined Immunodeficiency Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00008450
• Other study ID #: 1227.00
• Secondary ID: NCI-2010-0204512
• Status: Completed
• Phase: Phase 1
• Start date: August 11, 1997
• Est. completion date: December 26, 2018

Study information

• Verified date: July 2019
• Source: Fred Hutchinson Cancer Research Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: December 26, 2018
• Est. primary completion date: October 25, 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Adenosine Deaminase Deficiency
• Agammaglobulinemia
• Autosomal Recessive Disorder
• Disease
• Immune System Diseases
• Immune System Disorder
• Immunologic Deficiency Syndromes
• Purine-Nucleoside Phosphorylase Deficiency
• Severe Combined Immunodeficiency
• Severe Combined Immunodeficiency With Absence of T and B Cells
• X-Linked Combined Immunodeficiency Diseases
• X-Linked Severe Combined Immunodeficiency

Intervention

Procedure:
• Allogeneic Bone Marrow Transplantation
Undergo allogeneic bone marrow transplant

Drug:
• Cyclosporine
Given PO or IV

Other:
• Laboratory Biomarker Analysis
Correlative studies

Drug:
• Mycophenolate Mofetil
Given PO or IV

Procedure:
• Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation
Undergo nonmyeloablative allogeneic hematopoietic stem cell transplant

Radiation:
• Total-Body Irradiation
Undergo TBI

Locations

Country	Name	City	State
United States	Fred Hutch/University of Washington Cancer Consortium	Seattle	Washington

Sponsors (3)

Lead Sponsor	Collaborator
Fred Hutchinson Cancer Research Center	National Cancer Institute (NCI), National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mixed hematopoietic chimerism in a population of pediatric patients with immunodeficiency diseases	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.	Up to 5 years