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Adenosine Deaminase DeficiencyPhase 1NCT02022696

Treatment of SCID Due to ADA Deficiency With Autologous Transplantation of Cord Blood or Hematopoietic CD 34+ Cells After Addition of a Normal Human ADA cDNA by the EFS-ADA Lentiviral Vector

A Phase 1 study testing Lentiviral Gene Transfer in people with Adenosine Deaminase Deficiency and ADA-SCID, run by National Human Genome Research Institute (NHGRI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a clinical gene transfer study that aims to verify the safety and efficacy of the use of the EFS-ADA lentiviral vector to introduce the human adenosine deaminase (ADA) gene into the hematopoietic progenitors of patients affected with severe combined immunodeficiency due to ADA deficiency. Read more about this study

Who is it for?
Ages 1 year to 65 years
Conditions the study is for
Adenosine Deaminase Deficiency, ADA-SCID
What is being tested?
Lentiviral Gene Transfer
How many people
1 participants
Where
1 siteUnited States
Study dates
16 Dec 2013to 21 Sep 2017
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 1 year to 65 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Participants must satisfy Inclusion Criteria I, II, and III.
  • Children greater than or equal to 1.0 month 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, skin fibroblasts 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,
Show all 53Show fewer
  • OR
  • Evidence of severe immunologic deficiency in subject prior to institution of immune restorative therapy, based on lymphopenia (absolute lymphocyte count <200/microliters) or severely decreased T lymphocyte blastogenic responses to phytohemagglutinin (DeltaCPM<5,000),
  • Ineligible for matched sibling allogeneic bone marrow transplantation due to 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 UCLA Office of Human Research Protection Program and National Human Genome Research Institute (NHGRI) Institutional Review Boards.
  • It is a policy of the NIH Clinical Center not to admit patients younger than 1 year of age and weighing less than 10 kg because of the inadequacy of the existing emergency and intensive care services for very young children. We will comply with such policy.
  • EXCLUSION CRITERIA (OBSERVED WITHIN 8 WEEKS OF ENTERING THIS TRIAL):
  • Age less than or equal to 1.0 months
  • Hematologic
  • Anemia (hemoglobin < 10.5 g/dl at < 2 years of age, or < 11.5 g/dl at > 2 years of age).
  • Neutropenia (absolute granulocyte count <500/mm(3). If ANC< 1,000, absence of myelodysplastic syndrome on bone marrow aspirate and biopsy and normal marrow cytogenetics.
  • Thrombocytopenia (platelet count < 150,000/mm(3), at any age).
  • PT or PTT > 2 times the upper limits of normal (patients with a correctable deficiency controlled on medication will not be excluded).
  • Cytogenetic abnormalities on peripheral blood or bone marrow or amniotic fluid (if available).
  • Infectious
  • Evidence of active opportunistic infection or infection with HIV-1, hepatitis B, CMV or parvovirus B 19 by DNA PCR within 30-90 days prior to bone marrow harvest.
  • Pulmonary
  • Resting O2 saturation by pulse oximetry < 95% on room air.
  • Chest x-ray indicating active or progressive pulmonary disease.
  • Cardiac
  • Abnormal electrocardiogram (EKG) indicating cardiac pathology.
  • Uncorrected congenital cardiac malformation with clinical symptomatology.
  • Active cardiac disease, including clinical evidence of congestive heart failure, cyanosis, hypotension.
  • Poor cardiac function as evidenced by LV ejection fraction < 40% on echocardiogram.
  • Neurologic
  • Significant neurologic abnormality by examination.
  • Uncontrolled seizure disorder.
  • Renal
  • Renal insufficiency: serum creatinine greater than or equal to 1.2 mg/dl, or greater than or equal to 3+ proteinuria.
  • Abnormal serum sodium, potassium, calcium, magnesium, phosphate at grade III or IV by Division of AIDS Toxicity Scale.
  • Hepatic/GI:
  • Serum transaminases > 5 times the upper limit of normal (ULN).
  • Serum bilirubin > 2 times ULN.
  • Serum glucose > 1.5 times ULN.
  • Intractable severe diarrhea.
  • Oncologic
  • 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.
  • Ineligible for autologous HSCT by the criteria at the clinical site.
  • 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.
  • DFSP is a rare, locally invasive tumor with low metastatic potential. Patients receiving active anti-neoplastic therapy for any cancer, including DFSP, are not eligible. Patients with DFSP who are not being treated with active anti-neoplastic therapy at the time of enrollment AND have no plan to receive active anti-neoplastic therapy in the absence of progressive malignant disease AND whose DFSP is not expected to be life-limiting within the five years following the infusion of genetically corrected cells are eligible.
  • Patients with DFSP, for whom radiation or chemotherapy has been chosen, would remain ineligible during treatment, as the interaction of busulfan and the experimental gene transfer vectors with active anti-neoplastic therapy is difficult to predict and could reasonably be expected to be deleterious due to overlapping toxicities. When anti-neoplastic therapy is concluded, patients with ADA-SCID and a history of DFSP can be included.

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, 20892

Other trials in United States

About this study

This is a clinical gene transfer study that aims to verify the safety and efficacy of the use of the EFS-ADA lentiviral vector to introduce the human adenosine deaminase (ADA) gene into the hematopoietic progenitors of patients affected with severe combined immunodeficiency due to ADA deficiency. The EFS-ADA vector expresses the human ADA cDNA under the control of the elongation factor alpha short promoter (EFS). In addition, this protocol will examine the effects of the ADA gene transfer on the immune system of treated patients. Patients with ADA deficiency and ineligible for matched sibling allogeneic bone marrow transplantation are eligible to participate in the study. To increase engraftment and selected advantage or gene-corrected cells, busulfan will be used as a cytoreductive agent. Enzyme replacement (PEG-ADA) will be discontinued 30 days after infusion of gene-corrected cells. CD34+ hematopoietic progenitors will be isolated from the patient bone marrow, peripheral blood or cord blood, exposed to lentiviral vector-mediated gene transfer and re-infused into the patient through a peripheral vein. Clinical, immunological and molecular follow-up studies will assess safety, toxicity, and efficacy of the procedure.

Read the detailed description

This is a clinical gene transfer study that aims to verify the safety and efficacy of the use of the EFS-ADA lentiviral vector to introduce the human adenosine deaminase (ADA) gene into the hematopoietic progenitors of patients affected with severe combined immunodeficiency due to ADA deficiency. The EFS-ADA vector expresses the human ADA cDNA under the control of the elongation factor alpha short promoter (EFS). In addition, this protocol will examine the effects of the ADA gene transfer on the immune system of treated patients. Patients with ADA deficiency and ineligible for matched sibling allogeneic bone marrow transplantation are eligible to participate in the study. To increase engraftment and selected advantage or gene-corrected cells, busulfan will be used as a cytoreductive agent. Enzyme replacement (PEG-ADA) will be discontinued 30 days after infusion of gene-corrected cells. CD34+ hematopoietic progenitors will be isolated from the patient bone marrow, peripheral blood or cord blood, exposed to lentiviral vector-mediated gene transfer and re-infused into the patient through a peripheral vein. Clinical, immunological and molecular follow-up studies will assess safety, toxicity, and efficacy of the procedure.

Being tested
Lentiviral Gene Transfer
Keywords
Adenosine Deaminase Deficiency, Gene Therapy, Lentiviral Vectors
Medical subject headings
Severe combined immunodeficiency due to adenosine deaminase deficiency

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Lentiviral Gene TransferGenetic

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. To examine the safety of autologous transplantation of hematopoietic CD34+ cells transduced with the EFS-ADA lentiviral vector after non-myeloablative conditioning with busulfan and while withholding of PEG-ADA enzyme replacement therapy@@...

    Measured: 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Dec 2013 (estimated)
  2. Study start16 Dec 2013
  3. Primary completion16 Dec 2013
  4. Study completion21 Sep 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
1 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02022696
Sponsor's protocol ID
140038
Other IDs
14-HG-0038
Status last verified
21 Sep 2017
First submitted
20 Dec 2013
Last updated
27 Sep 2017
Results posted
No

Publications

  • Rosen FS, Cooper MD, Wedgwood RJ. The primary immunodeficiencies. N Engl J Med. 1995 Aug 17;333(7):431-40. doi: 10.1056/NEJM199508173330707. No abstract available.

    PubMed 7616993

  • Giblett ER, Anderson JE, Cohen F, Pollara B, Meuwissen HJ. Adenosine-deaminase deficiency in two patients with severely impaired cellular immunity. Lancet. 1972 Nov 18;2(7786):1067-9. doi: 10.1016/s0140-6736(72)92345-8. No abstract available.

    PubMed 4117384

  • Parkman R, Gelfand EW, Rosen FS, Sanderson A, Hirschhorn R. Severe combined immunodeficiency and adenosine deaminase deficiency. N Engl J Med. 1975 Apr 3;292(14):714-9. doi: 10.1056/NEJM197504032921402.

    PubMed 1089883

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Lentiviral Gene Transfer in people with Adenosine Deaminase Deficiency and ADA-SCID, run by National Human Genome Research Institute (NHGRI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 53 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

To examine the safety of autologous transplantation of hematopoietic CD34+ cells transduced with the EFS-ADA lentiviral vector after non-myeloablative conditioning with busulfan and while withholding of PEG-ADA enzyme replacement therapy@@... (time frame: 3 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02022696, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Sep 2017.

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