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
Information source: National Center for Research Resources (NCRR)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Gaucher's Disease
Intervention: human glucocerebrosidase gene into autologous peripheral blood stem cells (Gene Transfer)
Phase: Phase 1
Status: Completed
Sponsored by: National Center for Research Resources (NCRR) Official(s) and/or principal investigator(s):
John Barranger, Study Chair, Affiliation: University of Pittsburgh
Summary
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.
Clinical Details
Study design: Treatment
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.
Eligibility
Minimum age: 18 Years.
Maximum age: 65 Years.
Gender(s): Both.
Criteria:
PROTOCOL ENTRY CRITERIA:
- -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
Locations and Contacts
University of Pittsburgh, Pittsburgh, Pennsylvania 15260, United States
Additional Information
Starting date: November 1999
Last updated: June 23, 2005
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