A Study Evaluating the Safety and Efficacy of the LentiGlobin® BB305 Drug Product in Beta-Thalassemia Major Subjects
This trial is active, not recruiting.
|Treatment||lentiglobin® bb305 drug product|
|Phase||phase 1/phase 2|
|Start date||August 2013|
|End date||March 2018|
|Trial size||18 participants|
|Trial identifier||NCT01745120, HGB-204|
This is a non-randomized, open label, multi-site, single-dose, Phase 1/2 study in up to 18 subjects (including at least 3 adolescents between 12 and 17 years of age, inclusive) with beta-thalassemia major. The study will evaluate the safety and efficacy of autologous hematopoietic stem cell transplantation (HSCT) using LentiGlobin® BB305 Drug Product [autologous CD34+ hematopoietic stem cells transduced with LentiGlobin® BB305 Lentiviral Vector encoding the human β-A(T87Q)-globin gene].
|United States||No locations recruiting|
|Other countries||No locations recruiting|
|Los Angeles, CA||not available||no longer recruiting|
|Los Angeles, CA||UCLA / Jonsson Comprehensive Cancer Center||terminated|
|Oakland, CA||not available||no longer recruiting|
|Chicago, IL||not available||no longer recruiting|
|Philadelphia, PA||not available||no longer recruiting|
|Sydney, Australia||not available||no longer recruiting|
|Bangkok, Thailand||not available||no longer recruiting|
|Endpoint classification||safety/efficacy study|
|Intervention model||single group assignment|
Evaluate the efficacy of treatment with LentiGlobin® BB305 Drug Product in subjects with β-thalassemia major as measured by the production of hemoglobin containing the therapeutic globin protein [β-A(T87Q)-globin]
time frame: 18 - 24 months post-transplant
Evaluate the safety of treatment with LentiGlobin® BB305 Drug Product in subjects with β-thalassemia major as measured by the incidence of adverse events
time frame: 0-24 months post-transplant
Hematopoietic stem cell engraftment
time frame: 42 days post-transplant
Assess transgene marking as determined by measurement of the average vector copy number in peripheral blood and bone marrow
time frame: 0 - 24 months post-transplant
Male or female participants from 12 years up to 35 years old.
Inclusion criteria: - Subjects between 12 and 35 years of age, inclusive, at the time of consent/assent, and able to provide written consent/assent, if applicable. - Diagnosis of β-thalassemia major and a history of at least 100 mL/kg/year of pRBCs or ≥8 transfusions of pRBCs per year for the prior 2 years. - Eligible for allogeneic bone marrow transplant. - Treated and followed for at least the past 2 years in a specialized center that maintained detailed medical records, including transfusion history. Exclusion criteria: - Positive for presence of human immunodeficiency virus type 1 or 2 (HIV 1 and HIV 2). - A white blood cell (WBC) count <3 × 109/L, and / or platelet count <100 × 109/L if not due to hypersplenism. - Uncorrected bleeding disorder. - Any prior or current malignancy or myeloproliferative or immunodeficiency disorder. - Immediate family member with a known or suspected Familial Cancer Syndrome (including but not limited to hereditary breast and ovarian cancer syndrome, hereditary non-polyposis colorectal cancer syndrome and familial adenomatous polyposis). - Receipt of an allogeneic transplant. - Advanced liver disease, including persistent aspartate transaminase (AST), alanine transaminase (ALT), or total bilirubin value >3 × the upper limit of normal, liver biopsy demonstrating cirrhosis, extensive bridging fibrosis, or active hepatitis. - Kidney disease with a calculated creatinine clearance <30% normal value. - Uncontrolled seizure disorder. - Diffusion capacity of carbon monoxide (DLco) <50% of predicted (corrected for hemoglobin). - A cardiac T2* <10 ms by magnetic resonance imaging (MRI). - Any other evidence of severe iron overload that, in the Investigator's opinion, warrants exclusion. - Clinically significant pulmonary hypertension, as defined by the requirement for ongoing pharmacologic treatment or the consistent or intermittent use of supplemental home oxygen. - Participation in another clinical study with an investigational drug within 30 days of Screening. - Any prior or current malignancy or myeloproliferative disorder. - Prior receipt of gene therapy.
|Official title||A Phase 1/2 Open Label Study Evaluating the Safety and Efficacy of Gene Therapy in Subjects With β-Thalassemia Major by Transplantation of Autologous CD34+ Cells Transduced Ex Vivo With a Lentiviral β-A(T87Q)-Globin Vector (LentiGlobin® BB305 Drug Product)|
|Description||Subject participation for this study will be 2 years. Subjects who enroll in this study will be asked to participate in a subsequent long-term follow up study that will monitor the safety and efficacy of the treatment they receive for up to 13 years post-transplant.|
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