heterozygous beta 0-thalassemia and hemoglobin E transfusion-dependent beta-thalassemia (TDT) TDT, Beta 0/Beta E TDT
Conditions
Interventions
The day of BG1 infusion will be defined as Day 0. A single dose of BG1 will be administered at least 48 hours after the completion of busulfan administration. On Day 0, the participant will receive th
Transplantation of Autologous CD34+ Human Hematopoietic Stem Cells Transduced Ex Vivo with a beta A-T87Q-Globin Lentiviral Vector (BG1 Gene Therapy Product)
Sponsors
Program Management Unit Competitiveness
Eligibility
Sex/Gender
All
Age
13 Years to 35 Years
Inclusion criteria
Inclusion criteria: 1. Age between 13 and 35 years, inclusive of the date of informed consent 2. Able to sign written informed consent or assent, when applicable 3. Diagnosis of beta0/betaE transfusion-dependent beta-thalassemia (TDT) as defined by 3.1Documented compound heterozygous beta0-thalassemia and hemoglobin E (beta0/betaE) Patients may be enrolled based on a medical record, but confirmation of the genotypes using the study central laboratory are required before myeloablative conditioning. Mutations causing beta0-thalassemia are defined using the HbVar database. A mutation causing HbE is codon 26 (G>A) mutation (HBB:c.79G>A). Patients with TDT caused by the combination of a severe beta+-thalassemia (IVS-II-654 (C>T) mutation; HBB:c.316-197C>T) with a HbE (severe beta+/betaE), will also be included. 3.2 A history of at least 100 mL/kg/year or 10 units/year of packed RBC transfusions in the prior 2 years before signing written informed consent 4. Karnofsky performance status of greater than or equal to 80% for patients aged greater than or equal to 16 years, or Lansky performance status of greater than or equal to 80% for those aged <16 years 5. Eligible for an autologous stem cell transplant as judged by the investigator 6. Baseline average pre-transfusion Hb levels of greater than or equal to 9 g/dL for at least 6 months 7. Agree to use an acceptable contraceptive method(s) through at least 6 months after BG1 infusion in both male participants and female participants of childbearing potential. Female participants of childbearing potential are defined as those who have an intact uterus and at least 1 ovary and have menstruation at least once in the last 12 months.
Exclusion criteria
Exclusion criteria: 1. Available 10/10 HLA-matched related donor 2. Prior allo-HSCT 3. Have alfa-thalassemia and >1 alfa-chain deletion or alfa-multiplications 4. Have a beta 0/beta 0 thalassemia genotype or homozygous severe beta+-thalassemia (IVS-I-110 (G>A)) mutation or sickle cell beta-thalassemia variant 5. Clinically significant and active bacterial, viral, fungal, or parasitic infection as determined by the investigator 6. White blood cell count of platelet of less than three billion per liter or platelet count of less than 50 billion per liter not related to hypersplenism based on the investigator's judgment 7. History of a significant bleeding disorder 8. History of any illness(es) or any clinical condition(s) that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering the investigational product to the patient. This may include, but is not limited to, an immediate family member with a known family cancer syndrome, a history of cardiovascular or central nervous system disease, a history or a presence of clinically significant pathology, a history of uncontrolled seizure disorders, or a history of clinically significant psychiatric disorders.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| sustained production of HbAT87Q 6 months between Month 18 and Month 24 post-BG1 infusion HbAT87Q,successful neutrophil engraftment within 28 days after BG1 infusion ANC,Time to neutrophil engraftment After BG1 infusion first day of 3 consecutive days with ANC greater than or equal to 500/microliter after BG1 infusion,Time to platelet engraftment After BG1 infusion first day of 3 consecutive days with platelet greater than or equal to 20,000/microliter after BG1 infusion,,adverse events After BG1 infusion clinical laboratory values, and vital signs,Incidence of transplant-related mortality within 100 days and within 1 year post-BG1 infusion death possibly related to the transplantation procedure,All-cause mortality (or overall survival) After BG1 infusion death ,Detection of vector-derived RCL and Incidence of insertional oncogenesis After BG1 infusion insertional mutagenesis resulting in oncogenesis | — |
Secondary
| Measure | Time frame |
|---|---|
| Change in transfusion requirements per month and per year post-BG1 infusion red-cell volume [mL/kg] and number of transfusion,Proportion of the participants achieving sustained transfusion reduction a period of at least 6 months (sustained TR6) at the time of analysis starting 3 months after BG1 infusion annualized volume of packed RBC transfusion,Proportion of the participants achieving sustained transfusion independence a period of at least 6 months (sustained TI6) at the time of analysis starting 3 months after BG1 infusion absence of transfusions,Proportion of the participants achieving sustained transfusion reduction a period of at least 12 months (sustained TR12) at the time of analysis starting 3 months after BG1 infusion annualized volume of packed RBC transfusion,Proportion of the participants achieving sustained transfusion independence a period of at least 12 months (sustained TI12) at the time of analysis starting 3 months after BG1 infusion absence of transfusions,Change in pre-transfusion total hemoglobin (Hb) concentration from baseline over time Hb,Change in the production (concentration) of HbAT87Q from baseline over time HbAT87Q,Change in biological markers of iron metabolism, hemolysis, and dyserythropoiesis from baseline overtime iron study and Hb,Change in parameters of iron overload from baseline overtime, on months 12 and 24 Liver iron concentration (LIC) and Cardiac iron content (CIC) as assessed by T2* magnetic resonance imaging (MRI), Serum ferritin level,Proportion of the participants receiving iron chelation therapy over time receiving iron chelation therapy,Change in patient-reported outcomes (PROs) from baseline over time EQ-5D-5L, EQ-5D-Y, FACT-BMT, PedsQL | — |
Countries
Thailand
Contacts
Public ContactSuradej Hongeng
Ramathibodi Hospital, Mahidol University
Outcome results
None listed