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

Fred Hutchinson Cancer Center (FHCC)

Status and phase: Completed; Phase 1

Conditions: X-Linked Severe Combined Immunodeficiency; Immune System Disorder; Adenosine Deaminase Deficiency; Severe Combined Immunodeficiency With Absence of T and B Cells; Purine-Nucleoside Phosphorylase Deficiency; Autosomal Recessive Disorder; Severe Combined Immunodeficiency

Treatments: Other: Laboratory Biomarker Analysis; Drug: Cyclosporine; Procedure: Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation; Procedure: Allogeneic Bone Marrow Transplantation; Drug: Mycophenolate Mofetil; Radiation: Total-Body Irradiation

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00008450

P01HL036444 (U.S. NIH Grant/Contract)

1227.00 (Other Identifier)

P30CA015704 (U.S. NIH Grant/Contract)

NCI-2010-02045 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 6 patients

Sex: All

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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6 participants in 1 patient group

Treatment (cyclosporine, mycophenolate mofetil, transplant)

Experimental group

Description:

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.

Treatment:

Radiation: Total-Body Irradiation

Drug: Mycophenolate Mofetil

Other: Laboratory Biomarker Analysis

Procedure: Allogeneic Bone Marrow Transplantation

Procedure: Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation

Drug: Cyclosporine