Long-term Follow-up of Subjects With Transfusion-Dependent β-Thalassemia (TDT) Treated With Ex Vivo Gene Therapy

NCT02633943 | Active Not Recruiting FDA Drug

• 1 other identifier: LTF-303
• Study Type: observational
• Target: 66
• Locations: 8 countries
• Sites: 15

Brief Summary

This is a multi-center, long-term safety and efficacy follow-up study for subjects with transfusion-dependent β-thalassemia (TDT) who have been treated with ex vivo gene therapy drug product in bluebird bio-sponsored parent clinical studies. After completing the parent clinical studies (approximately 2 years), eligible subjects will be followed for an additional 13 years for a total of 15 years post-drug product infusion. No investigational drug product will be administered in this study.

Conditions

Transfusion-dependent Beta-Thalassemia

Outcome Measures

Primary Outcomes (4)

• The number of subjects with malignancies

  Up to 15 years post-drug product infusion

• The number of subjects with immune-related AEs

  Up to 15 years post-drug product infusion

• The number of subjects with new or worsening hematologic disorders

  Up to 15 years post-drug product infusion

• The number of subjects with new or worsening neurologic disorders

  Up to 15 years post-drug product infusion

Secondary Outcomes (37)

• βA-T87Q-globin expression

  Up to 15 years post-drug product infusion

• Proportion of subjects treated with beti-cel who achieved Transfusion Independence (TI)

  Up to 15 years post-drug product infusion

• Proportion of subjects treated with beti-cel who achieved Transfusion Independence at yearly timepoints

  Up to 15 years post-drug product infusion

• Time from drug product infusion to achievement of Transfusion Independence (in parent study or Study LTF-303)

  Up to 15 years post-drug product infusion

• Duration of Transfusion Independence

  Up to 15 years post-drug product infusion

Study Arms (1)

Subjects with Transfusion-Dependent β-Thalassemia

Long-term follow-up for participants treated with ex vivo gene therapy product in applicable bluebird bio-sponsored parent clinical trials and who agreed to participate in this study. Participants will be followed in this study for 13 years (for a total of 15 years of follow-up after drug product infusion in the parent studies)

Other: Safety and efficacy assessments

Interventions

Safety and efficacy assessments OTHER

Genetic: No interventional drug product utilized in this follow-up study Participants received a single IV infusion of LentiGlobin BB305 Drug Product in the parent studies. Vector copy number (VCN) measurement, safety evaluations, disease-specific assessments, and assessments to monitor for long-term effects of autologous transplant are conducted in this study.

Subjects with Transfusion-Dependent β-Thalassemia

Eligibility Criteria

• Age: 0 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Subjects with transfusion-dependent β-thalassemia who have been treated with ex vivo gene therapy product in bluebird bio-sponsored clinical studies

You may qualify if:

• Provision of written informed consent for this study by subjects, or as applicable, subject's parent(s)/legal guardian(s)
• Treated with drug product for therapy of transfusion-dependent β-thalassemia in a bluebird bio-sponsored clinical study

Sponsors & Collaborators

• Genetix Biotherapeutics Inc.: lead

Study Sites (15)

Unknown Facility

Oakland, California, United States

Location

Unknown Facility

Chicago, Illinois, United States

Location

Unknown Facility

Bethesda, Maryland, United States

Location

Unknown Facility

New York, New York, United States

Location

Unknown Facility

Philadelphia, Pennsylvania, United States

Location

Unknown Facility

Charleston, South Carolina, United States

Location

Unknown Facility

Sydney, Australia

Location

Unknown Facility

Marseille, France

Location

Unknown Facility

Paris, France

Location

Unknown Facility

Hanover, Germany

Location

Unknown Facility

Heidelberg, Germany

Location

Unknown Facility

Thessaloniki, Greece

Location

Unknown Facility

Rome, Italy

Location

Unknown Facility

Bangkok, Thailand

Location

Unknown Facility

London, United Kingdom

Location

Related Publications (3)

• Kwiatkowski JL, Thompson AA, Schneiderman J, Thuret I, Kulozik AE, Yannaki E, Cavazzana M, Hongeng S, Olson TS, Sauer MG, Thrasher AJ, Lal A, Rasko JE, Kunz JB, Kinney MA, Chawla A, Ali S, Tao G, Thakar H, Paramore C, Witthuhn N, Walters MC, Locatelli F. Long-term efficacy and safety results of betibeglogene autotemcel gene therapy for transfusion-dependent beta-thalassemia. Blood. 2026 Jan 12:blood.2025029196. doi: 10.1182/blood.2025029196. Online ahead of print.

  PMID: 41525466 DERIVED

• Kwiatkowski JL, Walters MC, Hongeng S, Yannaki E, Kulozik AE, Kunz JB, Sauer MG, Thrasher AJ, Thuret I, Lal A, Tao G, Ali S, Thakar HL, Elliot H, Lodaya A, Lee J, Colvin RA, Locatelli F, Thompson AA. Betibeglogene autotemcel gene therapy in patients with transfusion-dependent, severe genotype beta-thalassaemia (HGB-212): a non-randomised, multicentre, single-arm, open-label, single-dose, phase 3 trial. Lancet. 2024 Nov 30;404(10468):2175-2186. doi: 10.1016/S0140-6736(24)01884-1. Epub 2024 Nov 8.

  PMID: 39527960 DERIVED

• Magrin E, Semeraro M, Hebert N, Joseph L, Magnani A, Chalumeau A, Gabrion A, Roudaut C, Marouene J, Lefrere F, Diana JS, Denis A, Neven B, Funck-Brentano I, Negre O, Renolleau S, Brousse V, Kiger L, Touzot F, Poirot C, Bourget P, El Nemer W, Blanche S, Treluyer JM, Asmal M, Walls C, Beuzard Y, Schmidt M, Hacein-Bey-Abina S, Asnafi V, Guichard I, Poiree M, Monpoux F, Touraine P, Brouzes C, de Montalembert M, Payen E, Six E, Ribeil JA, Miccio A, Bartolucci P, Leboulch P, Cavazzana M. Long-term outcomes of lentiviral gene therapy for the beta-hemoglobinopathies: the HGB-205 trial. Nat Med. 2022 Jan;28(1):81-88. doi: 10.1038/s41591-021-01650-w. Epub 2022 Jan 24.

  PMID: 35075288 DERIVED

Related Links

• HGB-204 Clinicaltrials.gov
• HGB-205 Clinicaltrials.gov
• HGB-207 Clinicaltrials.gov
• HGB-212 Clinicaltrials.gov

MeSH Terms

Interventions

Safety

Intervention Hierarchy (Ancestors)

Accident Prevention; Accidents; Public Health; Environment and Public Health

Study Officials

• Himal L Thakar, MD

  bluebird bio, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 30, 2015
• First Posted: December 17, 2015
• Study Start: January 1, 2014
• Primary Completion (Estimated): November 1, 2035
• Study Completion (Estimated): November 1, 2035
• Last Updated: April 9, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share

Locations

GB (1); DE (2); GR (1); TH (1); FR (2); AU (1); IT (1); US (6)