Lentiviral Gene Therapy for Adenosine Deaminase (ADA) Deficiency

Related Clinical Trial
A Study to Assess a Physical Activity Program in Children, Adolescents and Young Adults Requiring Hematopoietic Stem Cell Allografts Matched Related and Unrelated Donor Stem Cell Transplantation for Severe Combined Immune Deficiency (SCID): Busulfan-based Conditioning With h-ATG, Radiation, and Sirolimus cliniMACs HUD for T Cell Depletion Cord Blood Stem Cell Transplantation Study (COBLT) Long Term Follow Up Of Patients Who Have Received Gene Therapy Or Gene Marked Products Lentiviral Gene Therapy for Adenosine Deaminase (ADA) Deficiency Genetic Basis of Immunodeficiency IMM 0212: Busulfan With Fludarabine and Antithymocyte Globulin as Preparative Therapy for Hematopoietic Stem Cell Transplant for the Treatment of Severe Congenital T-Cell Immunodeficiency Sirolimus Prophylaxis for aGVHD in TME SCID Study Through Imaging of Visceral Lymphoid Organs in Patients With SCID Who Have Recieved Bone Marrow Allograft Influences on Female Adolescents’ Decisions Regarding Testing for Carrier Status of XSCID Total-Body Irradiation Followed By Cyclosporine and Mycophenolate Mofetil in Treating Patients With Severe Combined Immunodeficiency Undergoing Donor Bone Marrow Transplant EZN-2279 in Patients With ADA-SCID AMG191 Conditioning/CD34+CD90 Stem Cell Transplant Study for SCID Patients Gene Therapy for X-linked Severe Combined Immunodeficiency (SCID-X1) Newborn Screening for Severe Combined Immunodeficiency (SCID) in a High-Risk Population Gene Transfer for Severe Combined Immunodeficiency, X-linked (SCID-X1) Using a Self-inactivating (SIN) Gammaretroviral Vector Phase I/II Trial of Lentiviral Gene Transfer for SCID-X1 With Low Dose Targeted Busulfan Conditioning Allogeneic SCT Of Pts With SCID And Other Primary Immunodeficiency Disorders Stem Cell Gene Therapy to Treat X-Linked Severe Combined Immunodeficiency (XSCID) Patients Treated for SCID (1968-Present) Clinical Characteristics and Genetic Profiles of Severe Combined Immunodeficiency in China Gene Therapy for ADA-SCID MND-ADA Transduction of CD34+ Cells From Children With ADA-SCID Transplantation of Hematopoietic Cells in Children With Severe Combined Immunodeficiency Syndrome Hematopoietic Stem Cell Transplantation (HSCT) for Children With SCID Utilizing Alemtuzumab, Plerixafor & Filgrastim Natural History Study of SCID Disorders Gene Transfer Therapy for Severe Combined Immunodeficieny Disease (SCID) Due to Adenosine Deaminase (ADA) Deficiency: A Natural History Study Safety and Early Efficacy Study of TBX-1400 in Patients With Severe Combined Immunodeficiency SCID Bu/Flu/ATG Study With T Cell Depletion Generalized Neonatal Screening of Severe Combined Immunodeficiencies Neonatal Screening of Severe Combined Immunodeficiencies Gene Therapy for X-linked Severe Combined Immunodeficiency An Observational LTFU Study for Patients Previously Treated With Autologous ex Vivo Gene Therapy for ADA-SCID Haplocompatible Transplant Using TCRα/β Depletion Followed by CD45RA-Depleted Donor Lymphocyte Infusions for Severe Combined Immunodeficiency (SCID) Registry Study of Revcovi Treatment in Patients With ADA-SCID Multi-center Clinical Study of Cord Blood Stem Cell Transplantation for SCID

Brief Title

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

Official Title

Phase I/II, Historical Controlled, Open-label, Non-randomised, Single-centre Trial to Assess the Safety and Efficacy of EF1αS-ADA Lentiviral Vector Mediated Gene Modification of Autologous CD34+ Cells From ADA-deficient Individuals

Brief Summary

      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.
    


Study Phase

Phase 1/Phase 2

Study Type

Interventional


Primary Outcome

Clinical progress of patients

Secondary Outcome

 Comparison of OS and EvFS outcomes at 2 and 3 years in subjects treated with IMP and patients who received allogeneic HSCT allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

Condition

Adenosine Deaminase Deficiency

Intervention

Infusion of autologous EFS-ADA LV CD34+ cells

Study Arms / Comparison Groups

 Gene Therapy
Description:  Infusion of autologous EFS-ADA LV CD34+ cells

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Genetic

Estimated Enrollment

36

Start Date

November 15, 2012

Completion Date

December 23, 2019

Primary Completion Date

December 23, 2019

Eligibility Criteria

        Gene Therapy (On Trial)

        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 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

        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)

        A group of patients were treated under CUP (GOSH special license) either because the study
        was not yet open and patients needed urgent treatment, or because they were outside of the
        inclusion/exclusion criteria or received IMP followed a different process (ie, received in
        two infusions). Patients followed the same protocol steps and study visits.

        Historical Control Group

        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 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
      

Gender

All

Ages

N/A - 15 Years

Accepts Healthy Volunteers

No

Contacts

Claire Booth, Dr, , 

Location Countries

United Kingdom

Location Countries

United Kingdom

Administrative Informations


NCT ID

NCT01380990

Organization ID

10-MI-29


Responsible Party

Sponsor

Study Sponsor

Great Ormond Street Hospital for Children NHS Foundation Trust

Collaborators

 Orchard Therapeutics

Study Sponsor

Claire Booth, Dr, Principal Investigator, Great Ormond Street Hospital NHS Foundation Trust


Verification Date

April 2020