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

Sponsor:	Fred Hutchinson Cancer Research Center
Collaborators:	National Cancer Institute (NCI) National Heart, Lung, and Blood Institute (NHLBI)
Information provided by:	Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:	NCT00008450

Purpose

RATIONALE: Giving total-body irradiation 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. PURPOSE: This clinical trial studies how well giving total-body irradiation followed by cyclosporine and mycophenolate mofetil works in treating patients with severe combined immunodeficiency undergoing donor bone marrow transplant

Condition	Intervention
Immune System Disorder Severe Combined Immunodeficiency	Drug: cyclosporine Drug: mycophenolate mofetil Other: laboratory biomarker analysis Genetic: DNA analysis Genetic: fluorescence in situ hybridization Other: flow cytometry Radiation: total-body irradiation Genetic: cytogenetic analysis Genetic: polymorphism analysis Procedure: allogeneic bone marrow transplantation Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
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

Resource links provided by NLM:

Genetics Home Reference related topics: adenosine deaminase deficiency complement factor I deficiency X-linked severe combined immunodeficiency ZAP70-related severe combined immunodeficiency

MedlinePlus related topics: Bone Marrow Transplantation Cancer

Drug Information available for: Cyclosporine Cyclosporin Mycophenolate mofetil hydrochloride Mycophenolate Mofetil

U.S. FDA Resources

Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:

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: Days 28, 56, 84, 180, 365 post-transplant and yearly thereafter for 5 years ] [ Designated as safety issue: No ]
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: At baseline, days 84, 180, and 365 post-transplant, and yearly thereafter for 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment:	12
Study Start Date:	August 1997
Estimated Primary Completion Date:	August 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Arm I Patients receive cyclosporine orally or IV on days -3 to 100 followed by a taper until day 180 and mycophenolate mofetil orally or IV on days 0-40 with a taper until day 96 in the absence of unacceptable toxicity. Unrelated donor recipients also undergo total-body irradiation on day 0. Patients undergo bone marrow transplantation on day 0.	Drug: cyclosporine Given orally or IV Other Names: ciclosporin cyclosporin cyclosporin A CYSP Sandimmune Drug: mycophenolate mofetil Given orally or IV Other Names: Cellcept MMF Other: laboratory biomarker analysis Correlative studies Genetic: DNA analysis Correlative studies Genetic: fluorescence in situ hybridization Correlative studies Other Name: fluorescence in situ hybridization (FISH) Other: flow cytometry Correlative studies Radiation: total-body irradiation Undergo total-body radiation Other Name: TBI Genetic: cytogenetic analysis Correlative studies Genetic: polymorphism analysis Correlative studies Procedure: allogeneic bone marrow transplantation Undergo allogeneic bone marrow transplantation Other Names: bone marrow therapy, allogeneic bone marrow therapy, allogenic transplantation, allogeneic bone marrow transplantation, allogenic bone marrow Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation Undergo nonmyeloablative allogeneic hematopoietic stem cell transplantation

Arms

Assigned Interventions

Experimental: Arm I

Patients receive cyclosporine orally or IV on days -3 to 100 followed by a taper until day 180 and mycophenolate mofetil orally or IV on days 0-40 with a taper until day 96 in the absence of unacceptable toxicity. Unrelated donor recipients also undergo total-body irradiation on day 0. Patients undergo bone marrow transplantation on day 0.

Drug: cyclosporine

Given orally or IV

Other Names:

ciclosporin
cyclosporin
cyclosporin A
CYSP
Sandimmune

Drug: mycophenolate mofetil

Given orally or IV

Other Names:

Cellcept
MMF

Other: laboratory biomarker analysis

Correlative studies

Genetic: DNA analysis

Correlative studies

Genetic: fluorescence in situ hybridization

Correlative studies

Other Name: fluorescence in situ hybridization (FISH)

Other: flow cytometry

Correlative studies

Radiation: total-body irradiation

Undergo total-body radiation

Other Name: TBI

Genetic: cytogenetic analysis

Correlative studies

Genetic: polymorphism analysis

Correlative studies

Procedure: allogeneic bone marrow transplantation

Undergo allogeneic bone marrow transplantation

Other Names:

bone marrow therapy, allogeneic
bone marrow therapy, allogenic
transplantation, allogeneic bone marrow
transplantation, allogenic bone marrow

Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation

Undergo nonmyeloablative allogeneic hematopoietic stem cell transplantation

Detailed Description:

OBJECTIVES: I. To safely establish partial lymphoid chimerism (1-95% donor CD3+ 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 or IV on days -3 to 100 followed by a taper until day 180 and mycophenolate mofetil orally or IV on days 0-40 with a taper until day 96 in the absence of unacceptable toxicity. Unrelated donor recipients also undergo total-body irradiation on day 0. Patients undergo bone marrow transplantation on day 0. After completion of study treatment, patients are followed up at 6 months and then every year for 5 years.

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients with Severe Combined Immunodeficiency Syndrome: 1) SCID with presence of B lymphocytes; a) X-linked SCID (presence of B lymphocytes), b) Autosomal recessive SCID
Patients with Severe Combined Immunodeficiency Syndrome: 2) SCID with absence of T and B lymphocytes
Patients with Severe Combined Immunodeficiency Syndrome: 3) Purine metabolite deficiencies, deficiencies of the purine metabolites; a) Adenosine deaminase (ADA) deficiency, b) Purine nucleoside phosphorylase (PNP) deficiency
DONOR: Related donor who is 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 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 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00008450

Locations

United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109

Sponsors and Collaborators

Fred Hutchinson Cancer Research Center

National Cancer Institute (NCI)

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

Principal Investigator:

Lauri Burroughs

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

More Information

No publications provided

Responsible Party:	Burroughs, Lauri, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
ClinicalTrials.gov Identifier:	NCT00008450 History of Changes
Other Study ID Numbers:	1227.00, NCI-2010-02045, P01HL036444
Study First Received:	January 6, 2001
Last Updated:	November 2, 2011
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Immunologic Deficiency Syndromes
Immune System Diseases
Severe Combined Immunodeficiency
Infant, Newborn, Diseases
DNA Repair-Deficiency Disorders
Metabolic Diseases
Cyclosporine
Cyclosporins
Mycophenolic Acid
Mycophenolate mofetil
Antifungal Agents
Anti-Infective Agents

Therapeutic Uses
Pharmacologic Actions
Dermatologic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antibiotics, Antineoplastic
Antineoplastic Agents

ClinicalTrials.gov processed this record on February 09, 2012