Pilot Study of Allogeneic Bone Marrow Transplantation Plus Cyclosporine and Mycophenolate Mofetil to Induce Mixed Hematopoietic Chimerism in Patients With Primary T-Cell Immunodeficiency Disorders - Full Text View

Sponsor:	Fred Hutchinson Cancer Research Center
Information provided by:	Office of Rare Diseases (ORD)
ClinicalTrials.gov Identifier:	NCT00008450

Purpose

OBJECTIVES: I. Determine the safety of cyclosporine and mycophenolate mofetil as a non-ablative conditioning and post-transplantation immunosuppression regimen in patients with primary T-cell immunodeficiency disorders who undergo HLA-matched related or unrelated bone marrow transplantation to induce mixed hematopoietic chimerism (establishment of 1-95% donor CD3+ cells).

II. Determine the kinetics of immune reconstitution of lymphoid cell subsets, T-cell function, and B-cell function after allogeneic bone marrow transplantation in this patient population.

Condition	Intervention	Phase
Purine-Pyrimidine Metabolism, Inborn Errors Wiskott-Aldrich Syndrome Bare Lymphocyte Syndrome Lymphopenia Job's Syndrome DiGeorge Syndrome Omenn Syndrome X-Linked Hyper IgM Syndrome Severe Combined Immunodeficiency Immunologic Deficiency Syndromes	Drug: Cyclosporine Drug: Mycophenolate mofetil	Phase I

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Parallel Assignment
Official Title:	Pilot Study of Allogeneic Bone Marrow Transplantation Plus Cyclosporine and Mycophenolate Mofetil to Induce Mixed Hematopoietic Chimerism in Patients With Primary T-Cell Immunodeficiency Disorders

Resource links provided by NLM:

Genetics Home Reference related topics: 22q11.2 deletion syndrome aceruloplasminemia adenosine deaminase deficiency hemophilia Job syndrome L1 syndrome thrombotic thrombocytopenic purpura Wiskott-Aldrich syndrome X-linked hyper IgM syndrome X-linked severe combined immunodeficiency

MedlinePlus related topics: Bone Marrow Transplantation

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

U.S. FDA Resources

Further study details as provided by Office of Rare Diseases (ORD):

Primary Outcome Measures:

Assessment of engraftment of donor T lymphocytes (1-95% donor CD3+ cells) [ Time Frame: 5 Years Post Transplant ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Kinetics of immune reconstitution following a non-lethal conditioning regimen in patients with immunodeficiency diseases [ Time Frame: 5 Years Post Transplant ] [ Designated as safety issue: No ]

Estimated Enrollment:	12
Study Start Date:	November 2000
Estimated Study Completion Date:	November 2014
Estimated Primary Completion Date:	November 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental All patients receive cyclosporine orally or IV on days -1 through 50 and oral mycophenolate mofetil on days 0 through 27 in the absence of unacceptable toxicity. All patients then undergo allogeneic bone marrow transplantation on day 0. Cyclosporine taper regimen begins on day 50 and continues through day 180 unless evidence of graft-versus-host disease.	Drug: Cyclosporine 2 mg/kg/dose (every 8 hours, less than 6kg) or 2 mg/kg/dose (every 12 hours, more than 6 kg) from day - 3 to day +100, followed by taper to day 180 Drug: Mycophenolate mofetil 15 mg/kg/dose every 8 hours until day 40, then taper until day +96
2: Experimental All patients receive cyclosporine orally or IV on days -1 through 50 and oral mycophenolate mofetil on days 0 through 27 in the absence of unacceptable toxicity. Unrelated donor recipients and non-SCID patients also undergo total body irradiation on day 0. All patients then undergo allogeneic bone marrow transplantation on day 0. Cyclosporine taper regimen begins on day 50 and continues through day 180 unless evidence of graft-versus-host disease.	Drug: Cyclosporine 2 mg/kg/dose (every 8 hours, less than 6kg) or 2 mg/kg/dose (every 12 hours, more than 6 kg) from day - 3 to day +100, followed by taper to day 180 Drug: Mycophenolate mofetil 15 mg/kg/dose every 8 hours until day 40, then taper until day +96

Arms

Assigned Interventions

1: Experimental

All patients receive cyclosporine orally or IV on days -1 through 50 and oral mycophenolate mofetil on days 0 through 27 in the absence of unacceptable toxicity. All patients then undergo allogeneic bone marrow transplantation on day 0. Cyclosporine taper regimen begins on day 50 and continues through day 180 unless evidence of graft-versus-host disease.

Drug: Cyclosporine

2 mg/kg/dose (every 8 hours, less than 6kg) or 2 mg/kg/dose (every 12 hours, more than 6 kg) from day - 3 to day +100, followed by taper to day 180

Drug: Mycophenolate mofetil

15 mg/kg/dose every 8 hours until day 40, then taper until day +96

2: Experimental

All patients receive cyclosporine orally or IV on days -1 through 50 and oral mycophenolate mofetil on days 0 through 27 in the absence of unacceptable toxicity. Unrelated donor recipients and non-SCID patients also undergo total body irradiation on day 0. All patients then undergo allogeneic bone marrow transplantation on day 0. Cyclosporine taper regimen begins on day 50 and continues through day 180 unless evidence of graft-versus-host disease.

Drug: Cyclosporine

2 mg/kg/dose (every 8 hours, less than 6kg) or 2 mg/kg/dose (every 12 hours, more than 6 kg) from day - 3 to day +100, followed by taper to day 180

Drug: Mycophenolate mofetil

15 mg/kg/dose every 8 hours until day 40, then taper until day +96

Detailed Description:

PROTOCOL OUTLINE: Patients are stratified according to type of primary T-cell immunodeficiency disorder (severe combined immunodeficiency syndrome (SCID) vs non-SCID) and donor status (related vs unrelated).

All patients receive cyclosporine orally or IV on days -1 through 50 and oral mycophenolate mofetil on days 0 through 27 in the absence of unacceptable toxicity. Unrelated donor recipients and non-SCID patients also undergo total body irradiation on day 0. All patients then undergo allogeneic bone marrow transplantation on day 0. Cyclosporine taper regimen begins on day 50 and continues through day 180 unless evidence of graft-versus-host disease.

Eligibility

Ages Eligible for Study:	up to 55 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

Histologically proven primary T-cell immunodeficiency disorder
Diminished immune responses based on primary defect in T-cell immunity (deficiency in T-cell number or function) including the following diagnostic categories:

Severe combined immunodeficiency syndromes (SCID): SCID with presence of B lymphocytes X-linked SCID. Autosomal recessive SCID. SCID with absence of T and B lymphocytes. Purine metabolite deficiency. Adenosine deaminase (ADA) deficiency. Purine nucleoside phosphorylase (PNP) deficiency.

Other T-cell immunodeficiencies: Bare lymphocyte syndrome (BLS). Omenn's syndrome. Hyper IgM syndrome. Wiskott-Aldrich syndrome. DiGeorge syndrome. Functional T cell defects. Defects in T cell receptor-CD3 complex. Interleukin-2 deficiency. Zap70 defect. Other T-cell functional defects defined by assays or clinical syndrome No viral-associated T-cell immunodeficiency disorder (e.g., HIV). Ineligible for conventional therapy HLA-matched bone marrow donor available HLA genotypically identical OR HLA phenotypically identical unrelated Matched serologically at HLA-A and B, and molecularly at HLA-C, DRB1, and DQB1 (mismatch at HLA-C allowed if matched molecularly at HLA-A and B).

--Prior/Concurrent Therapy--

No concurrent growth factors with mycophenolate mofetil

--Patient Characteristics--

Age: 55 and under
Life expectancy: At least 30 days
Other: No other disease or organ dysfunction that would limit survival to less than 30 days

Contacts and Locations

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

Locations

United States, Washington
Fred Hutchinson Cancer Research Center	Recruiting
Seattle, Washington, United States, 98109
Contact: Lauri Burroughs, MD lburroug@fhcrc.org

Sponsors and Collaborators

Fred Hutchinson Cancer Research Center

Investigators

Study Chair:

Lauri Burroughs, MD

Fred Hutchinson Cancer Research Center

More Information

No publications provided

Responsible Party:	Fred Hutchinson Cancer Research Center ( Lauri Burroughs, MD/ Primary Investigator )
Study ID Numbers:	199/13003, FHCRC-1227.00
Study First Received:	January 6, 2001
Last Updated:	September 2, 2008
ClinicalTrials.gov Identifier:	NCT00008450 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by Office of Rare Diseases (ORD):

DiGeorge syndrome
Job's syndrome
Omenn syndrome
Wiskott-Aldrich syndrome
X-linked hyper IgM syndrome
adenosine deaminase deficiency
bare lymphocyte syndrome
genetic diseases and dysmorphic syndromes

hematologic disorders
immunologic disorders and infectious disorders
lymphopenia
primary immunodeficiency disease
purine nucleoside phosphorylase deficiency
rare disease
severe combined immunodeficiency

Additional relevant MeSH terms:

Anti-Infective Agents
Cyclosporine
Molecular Mechanisms of Pharmacological Action
DNA Repair-Deficiency Disorders
Physiological Effects of Drugs
Mycophenolic Acid
Leukocyte Disorders
Cyclosporins
Metabolism, Inborn Errors
Job's Syndrome
Wiskott-Aldrich Syndrome
Pathologic Processes
Thrombocytopenia
Hemorrhagic Disorders
Therapeutic Uses

Mycophenolate mofetil
Infant, Newborn, Diseases
Dermatologic Agents
Phagocyte Bactericidal Dysfunction
Metabolic Diseases
Immune System Diseases
Hematologic Diseases
Severe Combined Immunodeficiency
Blood Coagulation Disorders
Blood Platelet Disorders
Lymphopenia
Endocrine System Diseases
Blood Coagulation Disorders, Inherited
Dysgammaglobulinemia
Leukopenia

ClinicalTrials.gov processed this record on November 05, 2009