Phase 2
N=10
MND-ADA Transduction of CD34+ Cells From Children With ADA-SCID
Severe Combined Immunodeficiency
Bottom Line
View on ClinicalTrials.gov: NCT00794508 ↗Enrolled (actual)
10
Serious AEs
50.0%
Results posted
May 2016
Primary outcome: Primary: Number of Participants With Adverse Events — 10; 9; 0; 10 participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- ADA gene transfer (Biological)
- Age
- Pediatric, Adult · 0+ yrs
- Sex
- All
- Sponsor
- Donald B. Kohn, M.D.
- Primary completion
- Dec 2014
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Adverse Events |
10; 9; 0; 10; 0 | — |
| SECONDARY Number of Participants With Greater Than 1% of Gene-Modified Cells in the Peripheral Blood |
10; 4 | — |
| SECONDARY Number of Participants Reaching the Normal Range of ADA Enzyme Activity |
9 | — |
Summary
Severe combined immune deficiency (SCID) may result from inherited deficiency of the enzyme adenosine deaminase (ADA). Children with ADA-deficient SCID often die from infections in infancy, unless treated with either a bone marrow transplant or with ongoing injections of PEG-ADA (Adagen) enzyme replacement therapy. Successful BMT requires the availability of a matched sibling donor for greatest success, and treatment using bone marrow from a less-well matched donor may have a higher rate of complications. PEG-ADA may restore and sustain immunity for many years, but is very expensive and requires injections 1-2 times per week on an ongoing basis. This clinical trial is evaluating the efficacy and safety of an alternative approach, by adding a normal copy of the human ADA gene into stem cells from the bone marrow of patients with ADA-deficient SCID. Eligible patients with ADA-deficient SCID, lacking a matched sibling donor, will be eligible if they meet entry criteria for adequate organ function and absence of active infections and following the informed consent process. Bone marrow will be collected from the back of the pelvis from the patients and processed in the laboratory to isolate the stem cells and add the human ADA gene using a retroviral vector. The patients will receive a moderate dosage of busulfan, a chemotherapy agent that eliminates some of the bone marrow stem cells in the patient, to "make space" for the gene-corrected stem cells to grow once they are given back by IV. Patients will be followed for two years to assess the potentially beneficial effects of the procedure on the function of their immune system and to assess possible side-effects. This gene transfer approach may provide a better and safer alternative for treatment of patients with ADA-deficient SCID.
Eligibility Criteria
Inclusion Criteria
- Children > 1.0 months of age with a diagnosis of ADA-deficient SCID based on:
- Confirmed absence ( 2 years of age,with normal serum iron studies). b. Neutropenia i. absolute granulocyte count 1 year of age)] and bone marrow aspirate and biopsy showing myelodysplasia or other gross abnormality. c. Thrombocytopenia (platelet count 150,000/mm3, at any age). d. PT or PTT >2X normal. e. Cytogenetic abnormalities on peripheral blood, or on cells collected by amniocentesis, if diagnosed in utero.
- Infectious
a. Evidence of active opportunistic infection or infection with HIV-1, hepatitis B, CMV or parvovirus B 19 by DNA PCR at time of assessment.
- Pulmonary
- Resting O2 saturation by pulse oximetry or = 1.2 mg/dl, or > or = 3+ proteinuria.
- Abnormal serum sodium, potassium, calcium, magnesium, phosphate at grade III or IV by Division of AIDS Toxicity Scale.
- Hepatic/GI:
- Serum transaminases > 5X normal.
- Serum bilirubin > 3.0 mg/dl.
- Serum glucose > 250mg/dl.
- Intractable severe diarrhea.
- Oncologic (see below*)
- Evidence of active malignant disease other than dermatofibrosarcoma protuberans (DFSP)
- Evidence of DFSP expected to require anti-neoplastic therapy within the 5 years following the infusion of genetically corrected cells
- Evidence of DFSP expected to be life limiting within the 5 years following the infusion of genetically corrected cells
- Known sensitivity to Busulfan
- General
- Expected survival <6 months.
- Pregnant.
- Major congenital anomaly.
- Medically eligible HLA-matched sibling.
- Other conditions which in the opinion of the P.I. or co-investigators, contra-indicate infusion of transduced cells or indicate patient's inability to follow protocol.
Data sourced from ClinicalTrials.gov (NCT00794508). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.