Status:
COMPLETED
MND-ADA Transduction of CD34+ Cells From Children With ADA-SCID
Lead Sponsor:
Donald B. Kohn, M.D.
Collaborating Sponsors:
FDA Office of Orphan Products Development
National Institutes of Health (NIH)
Conditions:
Severe Combined Immunodeficiency
Eligibility:
All Genders
1-18 years
Phase:
PHASE2
Brief 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 tre...
Detailed Description
The proposed study population is affected with adenosine deaminase-deficient severe combined immune deficiency (ADA-SCID), an autosomal recessive congenital immune deficiency. The basis of the propose...
Eligibility Criteria
Inclusion
- Children \> 1.0 months of age with a diagnosis of ADA-deficient SCID based on:
- Confirmed absence (\<3% of normal levels) of ADA enzymatic activity in peripheral blood or (for neonates) umbilical cord erythrocytes and/or leukocytes, or in cultured fetal cells derived from either chorionic villus biopsy or amniocentesis, prior to institution of enzyme replacement therapy.
- AND
- Evidence of severe combined immunodeficiency based on either:
- Family history of first order relative with ADA deficiency and clinical and laboratory evidence of severe immunologic deficiency,
- OR
- Evidence of severe immunologic deficiency in subject based on lymphopenia (absolute lymphocyte count \<200) or severely decreased T lymphocyte blastogenic responses to phytohemagglutinin (deltaCPM\<5,000), prior to institution of immune restorative therapy.
- OR
- Fulfillment of criterion:
- A in addition to evidence of genetic mutations affecting the ADA gene as determined by a CLIA certified laboratory and clinical evidence of combined immunodeficiency based on lymphopenia (absolute lymphocyte counts \<2SD of age-matched control values) and hypogammaglobulinemia (\<2SD of age-matched control values) or lack of specific antibody response to vaccination. In addition, for patients to be eligible under this criterion, they must present with a clinical history indicating life-threatening illness characterized by increased frequency and/or severity of infections resulting in hospitalization and/or the administration of intravenous antibiotics, for bacterial or opportunistic infection.
- Ineligible for allogeneic (matched sibling) bone marrow transplantation (BMT):
- Absence of a medically eligible HLA-identical sibling with normal immune function who may serve as an allogeneic bone marrow donor.
- Written informed consent according to guidelines of the Institutional Review Board (IRB) at the University of California Los Angeles (UCLA).
- This study is also open to delayed/late onset ADA-deficient patients who fulfill the criteria 1, 2.A, and 3 and who are not receiving PEG-ADA treatment after being invited to discuss all alternative treatment options with a physician not connected with the protocol.
Exclusion
- Age less than 1 month
- Hematologic
- a. Anemia (hemoglobin \<10.5 mg/dl at \<2 years of age, or \< 11.5 at \>2 years of age,with normal serum iron studies). b. Neutropenia i. absolute granulocyte count \<500/mm3 or ii. absolute granulocyte count 500-999/mm3 (1 month - 1 year of age) or 500-1499/mm3 (\> 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 \<95%.
- Chest x-ray indicating active or progressive pulmonary disease.
- Cardiac
- Abnormal electrocardiogram (EKG) indicating cardiac pathology.
- Uncorrected congenital cardiac malformation.
- Active cardiac disease, including clinical evidence of congestive heart failure,cyanosis, hypotension.
- Neurologic
- Significant neurologic abnormality by examination.
- Uncontrolled seizure disorder.
- Renal
- Renal insufficiency: serum creatinine \> 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.
Key Trial Info
Start Date :
November 1 2008
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
January 1 2015
Estimated Enrollment :
10 Patients enrolled
Trial Details
Trial ID
NCT00794508
Start Date
November 1 2008
End Date
January 1 2015
Last Update
April 23 2021
Active Locations (1)
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1
University of California, Los Angeles
Los Angeles, California, United States, 90095