ADA Gene Transfer Into Hematopoietic Stem/Progenitor Cells for the Treatment of ADA-SCID (Gene-ADA)

Fondazione Telethon

Status and phase: Completed; Phase 2

Conditions: Immunologic Deficiency Syndromes

Treatments: Drug: Busulfan; Genetic: Gene Therapy

Study type: Interventional

Funder types: Other

Identifiers

NCT00598481

15386-PRE21 (Other Identifier)

STRIM-004

Details and patient eligibility

About

This is a phase I/II protocol to evaluate the safety and efficacy of ADA gene transfer into hematopoietic stem/progenitor cells for the treatment of adenosine deaminase (ADA)-deficiency. This condition is an autosomal recessive form of Severe Combined Immunodeficiency (SCID) characterized by impaired immune responses, recurrent infections, failure to thrive and systemic toxicity due to accumulation of purine metabolites. Transplants from an human leukocyte-antigen (HLA)-identical sibling donor is the treatment of choice, but available for a minority of patients. The use of alternative bone marrow donors or enzyme replacement therapy is associated with important drawbacks. The drug product studied in this protocol consists of autologous cluster of differentiation (CD)34+ hematopoietic stem/progenitor cells engineered ex vivo with a retroviral vector encoding the therapeutic gene ADA. The engineered CD34+ cells are infused following a nonmyeloablative conditioning with busulfan to make space in the bone marrow. The study objectives are: a) to evaluate the safety and the clinical efficacy of gene therapy, in the absence of enzyme replacement therapy; b) to evaluate the biological activity (engraftment, ADA expression) of ADA transduced CD34+ cells and their hematopoietic progeny. c) to evaluate the immunological reconstitution and purine metabolism after gene therapy.

Full description

The safety of the study will be evaluated by description of all adverse events and adverse drug reactions.

The study is aimed at reaching the minimum sample size of ten patients.

Enrollment: 12 patients

Sex: All

Ages: Under 17 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• ADA-SCID with no HLA-identical sibling donor available
• pediatric age and at least one of the following criteria:
• inadequate immune response after PEG-ADA for > 6 months
• patients who discontinued PEG-ADA due to intolerance, allergy or auto-immunity
• patients for whom enzyme replacement therapy is not a life long therapeutic option

Exclusion criteria

• HIV infection
• history or current malignancy
• Patients who received a previous gene therapy treatment in the 12 months prior to receiving Strimvelis
• any other conditions dangerous for the patients according to the investigator

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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12 participants in 1 patient group

Gene Therapy

Experimental group

Description:

Infusion of autologous CD34+ cells transduced with retroviral vector encoding ADA after non-myeloablative conditioning with busulfan

Treatment:

Drug: Busulfan

Genetic: Gene Therapy