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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:  NCT00018018
Date of registration: 27/06/2001
Prospective Registration: Yes
Primary sponsor: National Human Genome Research Institute (NHGRI)
Public title: Gene Transfer Therapy for Severe Combined Immunodeficieny Disease (SCID) Due to Adenosine Deaminase (ADA) Deficiency
Scientific title: Treatment of SCID Due to ADA Deficiency With Autologous Cord Blood or Bone Marrow CD34+ Cells Transduced With a Human ADA Gene
Date of first enrolment: June 20, 2001
Target sample size: 8
Recruitment status: Completed
Study type:  Interventional
Study design:  Primary purpose: Treatment.  
Phase:  Phase 1
Countries of recruitment
United States
Name:     Robert A Sokolic, M.D.
Affiliation:  National Human Genome Research Institute (NHGRI)
Key inclusion & exclusion criteria


Patients will be enrolled into this study if they fulfill the following three criteria:

A. Patients of age greater than or equal to 1 month with a diagnosis of ADA-deficiency
based on:

1. Confirmed absence (less than 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.


2. 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 less than 200) or severely decreased T lymphocyte blastogenic
responses to phytohemagglutinin (cpm less than 5,000) prior to institution of immune
restorative therapy


3. Evidence of genetic mutations affecting the ADA gene as determined by the CLIA
certified laboratory and clinical evidence of combined immunodeficiency based on
lymphopenia (absolute lymphocyte counts less than 2SD of age-matched control values)
and hypogammaglobulinemia (less than 2SD of age-matched control values) or lack of
specific antibody response to vaccination. Evidence of life-threatening illness
(increased frequency and/or severity of infections resulting in hospitalization and/or
the administration of intravenous antibiotics) is necessary for patients to be
eligible under this criterion.

B. Patients ineligible for allogeneic (matched sibling) bone marrow transplantation (BMT)
based on:

1. Absence of a medically eligible HLA-identical sibling with normal immune function who
may serve as an allogenic bone marrow donor


2. Election by the parents or the adult patients to forgo allogeneic BMT in favor of
PEG-ADA enzyme therapy after being invited to discuss alternative treatment options
with a physician not connected with the protocol.

C. Written informed consent according to guidelines of the NHGRI IRB, NIH or the
Committee on Clinical Investigations (CCI) at Children's Hospital Los Angeles (CHLA).

This study is also open to delayed/late onset ADA-deficient patients who fulfill the
criteria A, B.1, and C and who are not receiving PEG-ADA treatment after being invited
to discuss all alternative treatment options with a physician not connected with the



a. Age less than 1 month


1. Anemia (hemoglobin less than 10.5 mg/dl, for subjects 2 years of age or less or
hemoglobin less than 11.5 mg/dl for subjects older than 2 years of age in the
presence of normal iron studies).

2. Neutropenia

i. absolute granulocyte count <500/mm (3) or

ii. absolute granulocyte count 500-999/mm (3) (ages 1-12 months) or 500-1,499/mm (3)
for ages >1 year) and bone marrow studies showing myelodysplasia or other gross

c. Thrombocytopenia (platelet count less than 150,000 mm(3) at any age)

d. PT or PTT greater than 2 times normal.

e. Cytogenic abnormalities on peripheral blood.


a. Evidence of active opportunistic infection or infection with HIV-1, hepatitis B,
CMV or parvovirus B19 by DNA PCR at time of assessment.


1. Resting O2 saturation by pulse oximetry less than 95%.

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


1. Abnormal electrocardiogram (EKG) indicating cardiac pathology.

2. Uncorrected congenital cardiac malformation.

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


1. Significant neurologic abnormality by examination.

2. Uncontrolled seizure disorder.


1. Renal insufficiency: for pediatric patients serum creatinine greater than or
equal to 1.2 mg/dl, or greater than or equal to 3+ proteinuria, for adults values
at grades greater than or equal to of the NCI Common Toxicity Criteria (CTC).

2. Abnormal serum sodium, potassium, calcium, magnesium, phosphate at grade III or
IV by DAIDS Toxicity Scale or NCI CTC.


1. Serum transaminases greater than 5 times normal.

2. Serum bilirubin greater than 3.0 mg/dl.

3. Serum glucose greater than 250 mg/dl.

4. Intractable severe diarrhea.


a. Evidence of active malignant disease other than dermatofibrosarcoma protuberans


1. Expected survival less than 6 months.

2. Major congenital anomaly.

3. Subject pregnant.

4. Medically eligible HLA-identical sibling available.

5. Known hypersensitivity to busulfan.

6. Other conditions which in the opinion of the P.I. or co-investigators,
contra-indicate infusion of transduced cells or ability to follow protocol.

Age minimum: 1 Month
Age maximum: N/A
Gender: All
Health Condition(s) or Problem(s) studied
Severe Combined Immunodeficiency Syndrome
Drug: CD34+ cells transduced with ADA retrovir
Primary Outcome(s)
Secondary Outcome(s)
Secondary ID(s)
Source(s) of Monetary Support
Please refer to primary and secondary sponsors
Secondary Sponsor(s)
Ethics review
Results available:
Date Posted:
Date Completed:
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