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

NCT00008450 | Completed Phase 1 DMC

• 4 other identifiers: 1227.00NCI-2010-02045P01HL036444P30CA015704
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (1)

Treatment (cyclosporine, mycophenolate mofetil, transplant)

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.

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

Interventions

Allogeneic Bone Marrow Transplantation PROCEDURE

Undergo allogeneic bone marrow transplant

Also known as: Allo BMT, Allogeneic BMT

Treatment (cyclosporine, mycophenolate mofetil, transplant)

Cyclosporine DRUG

Given PO or IV

Also known as: 27-400, Ciclosporin, CsA, Cyclosporin, Cyclosporin A, Gengraf, Neoral, OL 27-400, Sandimmun, Sandimmune, SangCya

Treatment (cyclosporine, mycophenolate mofetil, transplant)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (cyclosporine, mycophenolate mofetil, transplant)

Mycophenolate Mofetil DRUG

Given PO or IV

Also known as: Cellcept, MMF

Treatment (cyclosporine, mycophenolate mofetil, transplant)

Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo nonmyeloablative allogeneic hematopoietic stem cell transplant

Also known as: Non-myeloablative allogeneic transplant, Nonmyeloablative Stem Cell Transplantation, NST

Treatment (cyclosporine, mycophenolate mofetil, transplant)

Total-Body Irradiation RADIATION

Undergo TBI

Also known as: Total Body Irradiation, Whole-Body Irradiation

Treatment (cyclosporine, mycophenolate mofetil, transplant)

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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: 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

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Cancer Institute (NCI): collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Severe combined immunodeficiency due to adenosine deaminase deficiency; Immune System Diseases; Purine Nucleoside Phosphorylase Deficiency; Severe Combined Immunodeficiency; X-Linked Combined Immunodeficiency Diseases

Interventions

Cyclosporine; Cyclosporins; Mycophenolic Acid; Whole-Body Irradiation

Condition Hierarchy (Ancestors)

Primary Immunodeficiency Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Immunologic Deficiency Syndromes; Genetic Diseases, X-Linked

Intervention Hierarchy (Ancestors)

Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Radiotherapy; Therapeutics; Investigative Techniques

Study Officials

• Lauri Burroughs

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 6, 2001
• First Posted: January 8, 2001
• Study Start: August 11, 1997
• Primary Completion: October 25, 2011
• Study Completion: December 26, 2018
• Last Updated: July 29, 2019

Record last verified: 2019-07

Locations

US (1)