Lentiviral (LV) Gene Therapy for Adenosine Deaminase (ADA) Deficiency

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

36 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-11-15

Study Completion Date

2019-12-23

Brief Summary

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This is a historically controlled, non-randomized Phase I/II clinical trial to assess the safety and efficacy of autologous transplantation of CD34+ hematopoietic stem/progenitor cells (HSPCs), obtained from infants affected by ADA-SCID, following transduction of the HSPCs with a lentiviral vector (LV) carrying the human ADA complementary DNA (cDNA) under the control of the elongation factor 1 alpha shortened (EFS) promoter. Subjects treated in the trial receive the infusion of autologous, transduced cells following marrow cytoreduction with busulfan. The outcomes are compared to those observed in a historical control group of patients who received an allogeneic hematopoietic stem cell transplant (HSCT).

This Phase I/II clinical trial will be performed at Great Ormond Street Hospital (GOSH), London, United Kingdom.

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Detailed Description

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Conditions

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Adenosine Deaminase Deficiency Severe Combined Immunodeficiencies (SCID)

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Gene Therapy

Infusion of autologous EFS-ADA LV CD34+ cells

Group Type EXPERIMENTAL

Infusion of autologous EFS-ADA LV CD34+ cells

Intervention Type GENETIC

Autologous EFS-ADA LV CD34+ cells (OTL-101\*) are infused intravenously

Busulfan

Intervention Type DRUG

Busulfan is used for non-myeloablative conditioning

Peg-Ada

Intervention Type DRUG

Peg-Ada enzyme replacement therapy is discontinued at Day +3- (-3/+15 days) after successful engraftment

Historical Control Group

Historical data from ADA-SCID patients who were treated with Hematopoietic Stem Cell Transplantation (HSCT)

Group Type OTHER

Haematopoietic Stem Cell Transplantation (HSCT)

Intervention Type OTHER

Historical data from a database of ADA-SCID patients treated with allogeneic HSCT from GOSH will be collected as comparator group.

Interventions

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Infusion of autologous EFS-ADA LV CD34+ cells

Autologous EFS-ADA LV CD34+ cells (OTL-101\*) are infused intravenously

Intervention Type GENETIC

Haematopoietic Stem Cell Transplantation (HSCT)

Historical data from a database of ADA-SCID patients treated with allogeneic HSCT from GOSH will be collected as comparator group.

Intervention Type OTHER

Busulfan

Busulfan is used for non-myeloablative conditioning

Intervention Type DRUG

Peg-Ada

Peg-Ada enzyme replacement therapy is discontinued at Day +3- (-3/+15 days) after successful engraftment

Intervention Type DRUG

Other Intervention Names

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OTL-101*

Eligibility Criteria

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Inclusion Criteria

1. Diagnosis of ADA-SCID confirmed by DNA sequencing or by confirmed absence of \<3% of ADA enzymatic activity in peripheral blood (or for neonates) in umbilical cord blood erythrocytes and/or leukocytes or in cultured fetal cells derived from either chorionic villus biopsy or amniocentesis, prior to institution of Polyethylene glycol-modified ADA (PEG-ADA) replacement therapy
2. Patients who lack a fully Human leukocyte antigen (HLA)-matched family donor
3. Patients (male or female) \<5 years of age OR Patients (male or female) ≥ 5 years to 15 years of age who have preserved thymic function as evidenced by presence of \>10 % naïve T cells (CD4+45RA+27+ cells)
4. Parental/guardian signed informed consent

1. Diagnosis of ADA-SCID confirmed by DNA sequencing OR by confirmed absence of \<3% of ADA enzymatic activity in peripheral blood or (for neonates) in umbilical cord blood erythrocytes and/or leucocytes or in cultured foetal cells derived from either chorionic villus biopsy or amniocentesis, prior to institution of PEG-ADA replacement therapy
2. Patients (male or female) between 0-18 years at time of treatment
3. Patient treated with allogeneic haematopoietic stem cell transplantation since 2000

Exclusion Criteria

1. Cytogenetic abnormalities on peripheral blood
2. Evidence of active malignant disease
3. Known sensitivity to busulfan
4. If applicable, confirmed pregnancy (to be tested in patients above 12 years old)

Gene Therapy (CUP)

Historical Control Group

Maximum Eligible Age

15 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No