Autologous Transplant of EFS-ADA Modified Bone Marrow Cells for ADA-Deficient Severe Combined Immunodeficiency (SCID)
|ClinicalTrials.gov Identifier: NCT01852071|
Recruitment Status : Active, not recruiting
First Posted : May 13, 2013
Last Update Posted : September 27, 2017
|Condition or disease||Intervention/treatment||Phase|
|ADA-SCID||Genetic: EFS-ADA transduced CD34+ cells from the bone marrow||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official 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 Adenosine Deaminase (ADA)-Deficient Severe Combined Immunodeficiency (SCID)|
|Study Start Date :||May 2013|
|Estimated Primary Completion Date :||July 2018|
|Estimated Study Completion Date :||September 2018|
Experimental: Autologous transplant of ADA gene corrected bone marrow
Autologous transplantation of EFS-ADA transduced bone marrow CD34+ cells
Genetic: EFS-ADA transduced CD34+ cells from the bone marrow
Eligible subjects will undergo bone marrow harvest under general anesthesia. The marrow will be processed to isolate CD34+ cells and transduced with the EFS-ADA lentiviral vector. If sufficient cells are obtained, the subjects will undergo marrow cytoreduction with busulfan (4 mg/kg). If the transduced CD34+ final cell product meets all release criteria, the cells will be infused intravenously. PEG-ADA enzyme replacement therapy will be discontinued at day +30. After discharge from the hospital, the subject will be seen for interval history and examination by either their home physician, the principal investigator or a clinical investigator and have blood drawn at months 1, 2, 3, 4, 5, 6, 8, 10, 12, 15, 18, 21, and 24.
- Assess safety by recording clinical toxicities. [ Time Frame: 2 years ]Safety will be assessed by recording clinical adverse events.
- Assess safety by determining absence or presence of exposure to replication-competent lentivirus (RCL) [ Time Frame: 2 years ]Replication-competent lentivirus exposure will be assessed by polymerase chain reaction (PCR) to VSV-G protein.
- Assess safety by evaluating the absence or development of monoclonal expansion or leukoproliferative complications from vector insertional effects [ Time Frame: 2 years ]Monoclonal expansion of blood cells by vector-mediated activity will be assessed by nrLAM-PCR
- Overall survival [ Time Frame: 2 years ]Overall survival will be assessed
- Event-free survival [ Time Frame: 2 years ]Event-free survival will be assessed by determining the numbers of subjects who remain alive with adequate immune reconstitution and do not need an allogeneic hematopoietic stem cell transplant or re-institution of enzyme replacement therapy.
- Determine the frequency of gene marking in peripheral blood cells [ Time Frame: 2 years ]The frequency of peripheral blood cells containing the EFS-ADA transferred human ADA cDNA will be determined by qPCR as an index of gene transduction and engraftment of hematopoietic stem cells.
- Quantify clonal diversity of vector integrants [ Time Frame: 2 Years ]The clonal diversity of vector integration sites will be determined using nrLAM-PCR
- Quantify ADA enzyme activity in peripheral blood mononuclear cells [ Time Frame: 2 years ]The ADA enzymatic activity in peripheral blood mononuclear cells will be measured by biochemical assay.
- Quantify total adenine nucleotides in erythrocytes [ Time Frame: 2 years ]The levels of adenine nucleotides in erythrocytes will be measured by HPLC.
- Determine absolute lymphocytes on complete blood count [ Time Frame: 2 years ]The absolute lymphocyte counts (ALC) on complete blood count will be measured as an index of immune reconstitution.
- Quantify the absolute numbers T, B, and NK lymphocytes [ Time Frame: 2 years ]The absolute numbers of T, B and NK lymphocytes will be determined using flow cytometry as an index of immune reconstitution
- Assess lymphocyte mitogenic proliferation [ Time Frame: 2 years ]The proliferative responses of lymphocyte to mitogen stimulation will be quantified as an index of immune reconstitution.
- Measure quantitative immunoglobulins by class [ Time Frame: 2 years ]The levels of immunoglobulin classes (IgG, IgM, IgA) will be quantified as an index of immune reconstitution
- Quantify specific antibody responses [ Time Frame: 2 years ]The development of specific antibody responses to vaccine antigens will be quantified as an index of immune reconstitution
- Assess T lymphocyte reconstitution [ Time Frame: 2 years ]T lymphocyte reconstitution will be assessed by TCR Vbeta family usage enumeration by flow cytometry and TREC assay
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01852071
|United States, California|
|Mattel Children's Hospital, UCLA|
|Los Angeles, California, United States, 90095|
|United States, Maryland|
|Mark O. Hatfield Clinical Research Center, NIH|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Donald B Kohn, MD||University of California, Los Angeles|