OTL-300 is a gene therapy drug product consisting of autologous hematopoietic stem/progenitor cluster of differentiation (CD) 34+ cells genetically modified with a lentiviral vector (GLOBE) encoding the human beta globin gene. The TIGET-BTHAL is a phase I/II study evaluating safety and efficacy of OTL-300 in subjects with transfusion dependent beta-thalassemia for two years post gene-therapy. Subjects with rare disease who have undergone gene therapy are followed for efficacy and possible delayed adverse events. Thus, this study is designed to follow patients who have received gene therapy on TIGET-BTHAL for an additional six years (for a total of eight years).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
OTHER
Masking
NONE
Enrollment
9
Safety and efficacy assessment of OTL-300 in subjects with transfusion dependent beta-thalassemia will be performed.
Ospedale San Raffaele - Telethon Institute for Gene Therapy (OSR-TIGET)
Milan, Italy
Number of subjects with absence of abnormal clonal proliferation (ACP)
Clonal proliferation describes the selection and reproduction of only one type of cell.
Time frame: Up to 6 years
Number of subjects with Polyclonal engraftment
Integration site analysis will be performed on different hematopoietic lineages from peripheral blood and/or bone marrow. Polyclonality of hematopoiesis is defined as \>1000 unique integration sites retrieved at specified time points. The number of subjects with polyclonality of hematopoiesis will be estimated.
Time frame: Up to 6 years
Number of subjects with reduction in red blood cells (RBC) transfusion volume
Time frame: Up to 6 years
Number of subjects with reduction in transfusion rate up to transfusion independence
Time frame: Up to 6 years
Number of subjects with transfusion independence
Transfusion independence is defined as \<= 1 transfusion in the previous 6 months.
Time frame: Up to 6 years
Hemoglobin (Hb) levels in subjects achieving transfusion independence
Time frame: Up to 6 years
Number of subjects with sustained engraftment of genetically corrected cells
Engraftment will be assessed by vector-specific quantitative polymerase chain reaction (PCR) on bone marrow. Sustained engraftment is defined as \>=0.15 vector copy number (VCN)/genome in bone marrow erythroid cells.
Time frame: Up to 6 years
Number of subjects with overall survival
The number of subjects alive over all the trial.
Time frame: Up to 6 years
Number of subjects with adverse events (AEs), serious AEs (SAEs)
Time frame: Up to 6 years
Clinical chemistry laboratory parameters as a measure of safety
Time frame: Up to 6 years
Hematology laboratory parameters as a measure of safety
Time frame: Up to 6 years
Urinalysis as a measure of safety
Time frame: Up to 6 years
Occurrence of viral infections as a measure of safety
Microbiological laboratory tests will be performed to analyze the presence of hepatitis C virus ribonucleic acid (RNA), hepatitis B virus RNA, hepatitis B surface antigen, human T cell lymphotropic virus type 1-2 antibodies. Molecular tests will be performed for human immunodeficiency virus in peripheral blood or plasma.
Time frame: Up to 6 years
Screening for occurrence of antibodies against viruses and toxoplasma as a measure of safety
Immunological laboratory tests will be performed to analyze antibodies to Epstein-Barr virus, cytomegalovirus, herpes simplex virus 1-2, varicella zoster virus, toxoplasma.
Time frame: Up to 6 years
Functional assessment of cancer therapy-bone marrow transplant (FACT-BMT) scores
Time frame: Up to 6 years
Short-Form-36 (SF-36) scores
Impact of disease on overall QoL in adults will be measured using the SF-36.
Time frame: Up to 6 years
Pediatric Quality of Life (PedsQL) questionnaire scores
The PedsQL 4.0 generic core scale will be used to measure QoL in pediatric subjects.
Time frame: Up to 6 years
Evaluation of growth in pediatric subjects
Growth will be assessed by changes in height versus national growth charts and predicted genetic height.
Time frame: Up to 6 years
Assessment of hormonal levels in pediatric subjects
Time frame: Up to 6 years
Changes in puberty status as assessed by clinical examination
Time frame: Up to 6 years
Changes in puberty status as assessed by Tanner scale (TS)
Puberty will be assessed using TS.
Time frame: Up to 6 years
Changes in puberty status as assessed by general questioning
Time frame: Up to 6 years
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