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Phase I Study of Retrovirally Mediated Transfer of the Human Glucocerebrosidase Gene Into Peripheral Blood Stem Cells for Autologous Transplantation in Patients With Type I Gaucher Disease

This study has been completed.
University of Pittsburgh
Information provided by:
National Center for Research Resources (NCRR) Identifier:
First received: October 18, 1999
Last updated: June 23, 2005
Last verified: December 2003

OBJECTIVES: I. Transfer the human glucocerebrosidase (GC) gene into peripheral blood stem cells (PBSC) obtained from patients with type I Gaucher disease using a retroviral vector.

II. Transplant the autologous transduced PBSC in these patients. III. Measure the carriage and expression of the transferred gene and its duration in peripheral blood leukocytes.

IV. Assess the clinical effects of transplanting genetically corrected PBSC.

Condition Intervention Phase
Gaucher's Disease
Genetic: human glucocerebrosidase gene into autologous peripheral blood stem cells
Phase 1

Study Type: Interventional
Study Design: Primary Purpose: Treatment

Resource links provided by NLM:

Further study details as provided by National Center for Research Resources (NCRR):

Estimated Enrollment: 15
Study Start Date: November 1999
Detailed Description:

PROTOCOL OUTLINE: Patients undergo autologous transplantation using peripheral blood stems cells (PBSC) stimulated with filgrastim (G-CSF) and transduced with a retroviral vector containing the human glucocerebrosidase gene (R-GC). Patients may receive up to 4 transplants if a deficient glucocerebrosidase level is found in peripheral leukocytes 1 month following transplantation.

The G-CSF-stimulated PBSC are enriched for CD34-positive stem cells and transduced with the R-GC vector. Stem cells with normal gene activity are selected for transplantation.

Patients are followed every month for 6 months, every 6 months for 18 months, and then annually thereafter.


Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No


--Disease Characteristics-- Enzyme proven type I Gaucher disease Glucocerebrosidase (GC) activity less than 30% of normal GC mutation identified Significant signs and symptoms of disease prior to therapy initiation At least 1 of the following after 12 months of therapy: Liver at least 2 times normal size Spleen at least 5 times normal size Platelet count greater than 150,000/mm3 Clinical bone disease with pain, fractures, or infarctions Multiple sites of marrow involvement Angiotensin-converting enzyme at least 1.5 times normal No GC antibody At least 3 of the following responses to therapy: Hemoglobin increase of 2 g/dL Platelet count increase of 50% Spleen or liver size decrease at least 25% Improvement in MRI or x-ray of the bones Nontartrate inhibitable acid phosphatase decrease of 50% Angiotensin-converting enzyme decrease of 50% OR Previously untreated and immediate enzyme therapy would not be life saving Meets at least 2 of the following criteria: Spleen at least 5 times normal size or liver at least 2 times normal size by physical exam and MRI Hemoglobin less than 11 g/dL Platelet count less than 90,000/mm3 Disabling bone pain with degenerative changes on x-ray Multiple sites of bone marrow infiltration and evidence of bony changes Pulmonary compromise with clubbing and PaO2 less than 70 mm Hg Biopsy proven cirrhosis and elevated hepatic parenchymal enzymes Bleeding esophageal varices --Prior/Concurrent Therapy-- At least 3 months since any prior investigational therapy Concurrent enzyme replacement therapy may be tapered on study --Patient Characteristics-- HIV negative No malignant disease No known sensitivity to egg or murine products Not pregnant or nursing Fertile patients must use effective contraception

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Please refer to this study by its identifier: NCT00004294

United States, Pennsylvania
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15260
Sponsors and Collaborators
University of Pittsburgh
Study Chair: John Barranger University of Pittsburgh
  More Information

No publications provided Identifier: NCT00004294     History of Changes
Other Study ID Numbers: 199/11727, UPITTS-GAUCHER
Study First Received: October 18, 1999
Last Updated: June 23, 2005
Health Authority: United States: Federal Government

Keywords provided by National Center for Research Resources (NCRR):
Gaucher's disease
inborn errors of metabolism
rare disease

Additional relevant MeSH terms:
Gaucher Disease
Brain Diseases
Brain Diseases, Metabolic
Brain Diseases, Metabolic, Inborn
Central Nervous System Diseases
Genetic Diseases, Inborn
Lipid Metabolism Disorders
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Lysosomal Storage Diseases, Nervous System
Metabolic Diseases
Metabolism, Inborn Errors
Nervous System Diseases
Sphingolipidoses processed this record on November 25, 2014