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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:  NCT01852071
Date of registration: 07/05/2013
Prospective Registration: Yes
Primary sponsor: Orchard Therapeutics
Public title: Autologous CD34+ Hematopoietic Stem Cells Transduced ex Vivo With EFS Lentiviral Vector Encoding for the Human ADA Gene
Scientific title: Autologous Transplantation of Bone Marrow CD34+ Stem/Progenitor Cells After Addition of a Normal Human ADA cDNA by the EFS-ADA Lentiviral Vector for Severe Combined Immunodeficiency Due to Adenosine Deaminase Deficiency (ADA-SCID)
Date of first enrolment: August 2, 2013
Target sample size: 20
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 1/Phase 2
Countries of recruitment
United States
Name:     Donald B Kohn, MD
Affiliation:  University of California, Los Angeles
Key inclusion & exclusion criteria

Inclusion Criteria:

-Children = 1.0 months of age with a diagnosis of ADA-deficient SCID based on A. Decreased
ADA enzymatic activity in erythrocytes, leukocytes, skin fibroblasts, or in cultured fetal
cells to levels consistent with ADA-deficient SCID as determined by reference laboratory or
confirmed ADA gene mutation(s) known to cause disease , AND

B. Evidence of severe combined immunodeficiency based on either:

1. Family history of first order relative with ADA deficiency and clinical and laboratory
evidence of severe immunologic deficiency, OR

2. Evidence of severe immunologic deficiency in subject prior to institution of immune
restorative therapy, based on

1. lymphopenia (absolute lymphocyte count <400 cells/mcL) OR absence or low number
of T cells (absolute CD3+ count <300 cells/mcL) OR

2. severely decreased T lymphocyte blastogenic responses to phytohemagglutinin
(either <10% of lower limit of normal controls for the diagnostic laboratory,
<10% of the response of the normal control of the day, or stimulation index <10)

- Ineligible for matched sibling allogeneic bone marrow transplantation:
absence of a medically eligible HLA-identical sibling, with normal immune
function, who may serve as an allogeneic bone marrow donor

- Signed written informed consent according to guidelines of the Institutional
Review Board (IRB) (UCLA Office of Human Research Protection Program and
National Human Genome Research Institute (NHGRI) IRB

Exclusion Criteria:

1. Age = 1.0 months Appropriate organ function as outlined below must be observed within
60 days of entering this trial.

2. Hematologic

1. Anemia (hemoglobin < 10.5 g/dl at < 2 years of age, or < 11.5 g/dl at > 2 years
of age).

2. Neutropenia (absolute granulocyte count <500/mm3.

3. Thrombocytopenia (platelet count < 150,000/mm3, at any age).

4. International Normalised Ratio (INR) or Prothrombin Time (PT) > 2X the upper
limits of normal or Partial Thromboplastin Time (PTT) > 2.33X the upper limit of
normal (patients with a correctable deficiency controlled on medication will not
be excluded).

5. Cytogenetic abnormalities on peripheral blood or bone marrow or amniotic fluid
(if available).

6. Prior allogeneic Hematopoietic Stem Cell Transplant (HSCT) with cytoreductive

3. Infectious

a. Evidence of infection with HIV-1, hepatitis B, Hepatitis C, or parvovirus B 19 by
DNA Polymerase Chain Reaction (PCR) within 90 days prior to bone marrow harvest. If
other infection is present, it must be under control (e.g. stable or decreasing viral
load) at the time of screening

4. Pulmonary

1. Resting O2 saturation by pulse oximetry < 95% on room air.

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

5. Cardiac

1. Abnormal electrocardiogram (EKG) indicating cardiac pathology.

2. Uncorrected congenital cardiac malformation with clinical symptomatology.

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

4. Poor cardiac function as evidenced by LV ejection fraction < 40% on

6. Neurologic

1. Significant neurologic abnormality by examination.

2. Uncontrolled seizure disorder.

7. Renal

1. Renal insufficiency: serum creatinine >= 1.2 mg/dl, 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 the upper limit of normal (ULN).

2. Serum bilirubin > 2X ULN.

3. Serum glucose > 1.5x ULN.

4. Intractable severe diarrhea.

9. Oncologic

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. Ineligible for autologous HSCT by the criteria at the clinical site.

5. Other conditions which in the opinion of the principal investigator and/or
co-investigators, contra-indicate the bone marrow harvest, the administration of
busulfan, infusion of transduced cells or indicate the patient or patient's
parents/primary caregivers inability to follow protocol.

Age minimum: 1 Month
Age maximum: 17 Years
Gender: All
Health Condition(s) or Problem(s) studied
Drug: busulfan
Genetic: Infusion of autologous EFS-ADA LV CD34+ (OTL-101)
Primary Outcome(s)
Assess safety by determining absence or presence of exposure to replication-competent lentivirus (RCL) [Time Frame: 2 years]
Assess safety by evaluating the absence or development of monoclonal expansion or leukoproliferative complications from vector insertional effects [Time Frame: 2 years]
Assess safety by recording clinical toxicities. [Time Frame: 2 years]
Event-free survival [Time Frame: 1 year]
Overall survival [Time Frame: 1 year]
Secondary Outcome(s)
Event-free survival [Time Frame: 2 years]
Overall survival [Time Frame: 2 years]
Secondary ID(s)
Source(s) of Monetary Support
Please refer to primary and secondary sponsors
Secondary Sponsor(s)
National Heart, Lung, and Blood Institute (NHLBI)
National Human Genome Research Institute (NHGRI)
National Institute of Allergy and Infectious Diseases (NIAID)
University of California, Los Angeles
Ethics review
Results available:
Date Posted:
Date Completed:
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