World Health Organization site
Skip Navigation Links

Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Last refreshed on: 12 December 2020
Main ID:  NCT00794508
Date of registration: 19/11/2008
Prospective Registration: Yes
Primary sponsor: Donald B. Kohn, M.D.
Public title: MND-ADA Transduction of CD34+ Cells From Children With ADA-SCID
Scientific title: MND-ADA Transduction of CD34+ Cells From the Bone Marrow Of Children With Adenosine Deaminase (ADA)-Deficient Severe Combined Immunodeficiency (SCID): Effect of Discontinuation of PEG-ADA and Marrow Cytoreduction With Busulfan
Date of first enrolment: November 2008
Target sample size: 10
Recruitment status: Completed
Study type:  Interventional
Study design:  Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).  
Phase:  Phase 2
Countries of recruitment
United States
Name:     Donald B. Kohn, M.D.
Affiliation:  University of California, Los Angeles
Key inclusion & exclusion criteria

Inclusion Criteria:

1. 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.


- 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,


- 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.


- 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.

2. 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.

3. 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 Criteria:

1. Age less than 1 month

2. 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.

3. 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.

4. Pulmonary

1. Resting O2 saturation by pulse oximetry <95%.

2. Chest x-ray indicating active or progressive pulmonary disease.

5. Cardiac

1. Abnormal electrocardiogram (EKG) indicating cardiac pathology.

2. Uncorrected congenital cardiac malformation.

3. Active cardiac disease, including clinical evidence of congestive heart
failure,cyanosis, hypotension.

6. Neurologic

1. Significant neurologic abnormality by examination.

2. Uncontrolled seizure disorder.

7. Renal

1. Renal insufficiency: serum creatinine > or = 1.2 mg/dl, or > or = 3+ proteinuria.

2. Abnormal serum sodium, potassium, calcium, magnesium, phosphate at grade III or
IV by Division of AIDS Toxicity Scale.

8. Hepatic/GI:

1. Serum transaminases > 5X normal.

2. Serum bilirubin > 3.0 mg/dl.

3. Serum glucose > 250mg/dl.

4. Intractable severe diarrhea.

9. Oncologic (see below*)

1. Evidence of active malignant disease other than dermatofibrosarcoma protuberans

2. Evidence of DFSP expected to require anti-neoplastic therapy within the 5 years
following the infusion of genetically corrected cells

3. Evidence of DFSP expected to be life limiting within the 5 years following the
infusion of genetically corrected cells

10. Known sensitivity to Busulfan

11. General

1. Expected survival <6 months.

2. Pregnant.

3. Major congenital anomaly.

4. Medically eligible HLA-matched sibling.

5. 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.

Age minimum: 1 Month
Age maximum: 18 Years
Gender: All
Health Condition(s) or Problem(s) studied
Severe Combined Immunodeficiency
Biological: ADA gene transfer
Primary Outcome(s)
Number of Participants With Adverse Events [Time Frame: 2 years]
Secondary Outcome(s)
Number of Participants Reaching the Normal Range of ADA Enzyme Activity [Time Frame: 2 years]
Number of Participants With Greater Than 1% of Gene-Modified Cells in the Peripheral Blood [Time Frame: 2 years]
Secondary ID(s)
ADA Gene Therapy
Source(s) of Monetary Support
Please refer to primary and secondary sponsors
Secondary Sponsor(s)
FDA Office of Orphan Products Development
National Institutes of Health (NIH)
Ethics review
Results available: Yes
Date Posted: 30/05/2016
Date Completed:
Disclaimer: Trials posted on this search portal are not endorsed by WHO, but are provided as a service to our users. In no event shall the World Health Organization be liable for any damages arising from the use of the information linked to in this section. None of the information obtained through use of the search portal should in any way be used in clinical care without consulting a physician or licensed health professional. WHO is not responsible for the accuracy, completeness and/or use made of the content displayed for any trial record.
Copyright - World Health Organization - Version 3.6 - Version history