Autologous Transplant of EFS-ADA Modified Bone Marrow Cells for ADA-Deficient Severe Combined Immunodeficiency (SCID)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01852071|
Recruitment Status : Active, not recruiting
First Posted : May 13, 2013
Last Update Posted : August 24, 2018
|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 :||September 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
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|