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

NCT ID: NCT00008450

Last Updated: 2019-07-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

6 participants

Study Classification

INTERVENTIONAL

Study Start Date

1997-08-11

Study Completion Date

2018-12-26

Brief Summary

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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.

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Detailed Description

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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.

Conditions

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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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Allogeneic Bone Marrow Transplantation

Intervention Type PROCEDURE

Undergo allogeneic bone marrow transplant

Cyclosporine

Intervention Type DRUG

Given PO or IV

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Mycophenolate Mofetil

Intervention Type DRUG

Given PO or IV

Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation

Intervention Type PROCEDURE

Undergo nonmyeloablative allogeneic hematopoietic stem cell transplant

Total-Body Irradiation

Intervention Type RADIATION

Undergo TBI

Interventions

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Allogeneic Bone Marrow Transplantation

Undergo allogeneic bone marrow transplant

Intervention Type PROCEDURE

Cyclosporine

Given PO or IV

Intervention Type DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

Mycophenolate Mofetil

Given PO or IV

Intervention Type DRUG

Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation

Undergo nonmyeloablative allogeneic hematopoietic stem cell transplant

Intervention Type PROCEDURE

Total-Body Irradiation

Undergo TBI

Intervention Type RADIATION

Other Intervention Names

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Allo BMT Allogeneic BMT 27-400 Ciclosporin CsA Cyclosporin Cyclosporin A Gengraf Neoral OL 27-400 Sandimmun Sandimmune SangCya Cellcept MMF Non-myeloablative allogeneic transplant Nonmyeloablative Stem Cell Transplantation NST Total Body Irradiation Whole-Body Irradiation

Eligibility Criteria

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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
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role collaborator

Fred Hutchinson Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Lauri Burroughs

Role: PRINCIPAL_INVESTIGATOR

Fred Hutch/University of Washington Cancer Consortium

Locations

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Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, United States

Site Status

Countries

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United States

Other Identifiers

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NCI-2010-02045

Identifier Type: REGISTRY

Identifier Source: secondary_id

1227.00

Identifier Type: OTHER

Identifier Source: secondary_id

P01HL036444

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA015704

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1227.00

Identifier Type: -

Identifier Source: org_study_id

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