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

Long-term Follow-up of Subjects With Transfusion-Dependent β-Thalassemia (TDT) Treated With Ex Vivo Gene Therapy Using Autologous Hematopoietic Stem Cells Transduced With a Lentiviral Vector

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 study (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.

Study Overview

• Status: Active, not recruiting
• Conditions: Transfusion-dependent Beta-Thalassemia
• Intervention / Treatment: Other: Safety and efficacy assessments

• Study Type: Observational
• Enrollment (Actual): 66

Contacts and Locations

Study Locations

• Australia
  • Sydney, Australia
• France
  • Marseille, France
  • Paris, France
• Germany
  • Hannover, Germany
  • Heidelberg, Germany
• Greece
  • Thessaloníki, Greece
• Italy
  • Rome, Italy
• Thailand
  • Bangkok, Thailand
• United Kingdom
  • London, United Kingdom
• United States
  • California
    • Oakland, California, United States
  • Illinois
    • Chicago, Illinois, United States
  • Maryland
    • Bethesda, Maryland, United States
  • New York
    • New York, New York, United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States
  • South Carolina
    • Charleston, South Carolina, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 50 years (Child, Adult)
• Accepts Healthy Volunteers: No

• 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

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• There are no exclusion criteria for this study

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Subjects with Transfusion-Dependent β-Thalassemia; Subjects treated with ex vivo gene therapy product in an applicable bluebird bio-sponsored clinical trial who agree to participate in this long-term follow-up study	Other: Safety and efficacy assessments; Vector copy number (VCN) measurement, safety evaluations, disease-specific assessments, and assessments to monitor for long-term effects of autologous transplant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
βA-T87Q-globin expression	Median (min, max) βA-T87Q-globin expression	Up to 15 years post-drug product infusion
Proportion of subjects treated with beti-cel who achieved Transfusion Independence (TI)	Proportion of subjects who achieved TI, defined as a weighted average Hb ≥ 9 g/dL without any packed red blood cell (pRBC) transfusions for a continuous period of ≥ 12 months at any time after drug product infusion in parent study and/or Study LTF-303	Up to 15 years post-drug product infusion
Proportion of subjects treated with beti-cel who achieved Transfusion Independence at yearly timepoints	Proportion of subjects treated with beti-cel who achieved TI at yearly timepoints including Year 5, Year 10, and Year 15 post-drug product infusion, and at last follow-up	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
Weighted average Hb during Transfusion Independence		Up to 15 years post-drug product infusion
Time from drug product infusion to last pRBC transfusion (in parent study or Study LTF-303)		Up to 15 years post-drug product infusion
Time from last pRBC transfusion (in parent study or Study LTF-303) to last follow-up		Up to 15 years post-drug product infusion
Weighted average nadir Hb from 6 months post-drug product infusion (parent study) through last follow-up	Weighted average nadir Hb from 6 months post-drug product infusion (parent study) through last follow-up as compared to the weighted average nadir Hb during the 2 years prior to parent study enrollment	Up to 15 years post-drug product infusion
Unsupported total Hb levels over time through last follow-up	Unsupported total Hb level is defined as the total Hb measurement level without any acute or chronic pRBC transfusions within 60 days prior to the measurement date.	Up to 15 years post-drug product infusion
Proportion of subjects with unsupported total Hb levels ≥ 10 g/dL over time through last follow-up, including Year 5, Year 10, and Year 15		Up to 15 years post-drug product infusion
Proportion of subjects with unsupported total Hb levels ≥ 11 g/dL over time through last follow-up, including Year 5, Year 10, and Year 15		Up to 15 years post-drug product infusion
Proportion of subjects with unsupported total Hb levels ≥ 12 g/dL over time through last follow-up, including Year 5, Year 10, and Year 15		Up to 15 years post-drug product infusion
Proportion of subjects with unsupported total Hb levels ≥ 13 g/dL over time through last follow-up, including Year 5, Year 10, and Year 15		Up to 15 years post-drug product infusion
Proportion of subjects with unsupported total Hb levels ≥ 14 g/dL over time through last follow-up, including Year 5, Year 10, and Year 15		Up to 15 years post-drug product infusion
Liver iron content (LIC) by magnetic resonance imaging (MRI)/Superconducting Quantum Interference Device (SQUID) over time at yearly timepoints through last follow-up		Up to 15 years post-drug product infusion
Change from parent study baseline in LIC by MRI/SQUID over time at yearly timepoints through last follow-up		Up to 15 years post-drug product infusion
Cardiac T2* by MRI over time at yearly timepoints through last follow-up		Up to 15 years post-drug product infusion
Change from parent study baseline in cardiac T2* by MRI over time at yearly timepoints through last follow-up		Up to 15 years post-drug product infusion
Serum ferritin over time at yearly timepoints through last follow-up		Up to 15 years post-drug product infusion
Change from parent study baseline in serum ferritin over time at yearly timepoints through last follow-up		Up to 15 years post-drug product infusion
Number of subjects who stopped iron chelation post-DP infusion	Defined as subjects who stopped iron chelation or never restarted chelation after DP infusion.	Up to 15 years post-drug product infusion
Number of subjects who stopped iron chelation for at least 6 months post-drug product infusion		Up to 15 years post-drug product infusion
Time from stopping chelation to last follow-up	Among subjects that never restart chelation after DP infusion.	Up to 15 years post-drug product infusion
Proportion of subjects using phlebotomy therapy post-drug product infusion		Up to 15 years post-drug product infusion
Annualized frequency of phlebotomy therapy usage	Annualized frequency of phlebotomy therapy usage is defined as the number of procedures per year, calculated from DP infusion through last follow-up.	Up to 15 years post-drug product infusion
Reticulocyte counts over time at yearly timepoints through last follow-up		Up to 15 years post-drug product infusion
Change from Baseline in reticulocyte counts at yearly timepoints through last follow-up	Baseline defined as value closest, but prior to, conditioning in parent study.	15 years post-drug product infusion
Proportion of subject with nucleated RBC over time at yearly timepoints through last follow-up		Up to 15 years post-drug product infusion
Change from Baseline in patient reported outcome (PRO) as assessed by Pediatric Quality of Life Inventory (PedsQL) Generic Core Scale (GCS) Score		5 years post-drug product infusion
Change from Baseline in PRO as assessed by EuroQol-5D Youth version (EQ-5D-Y)		5 years post-drug product infusion
Change from Baseline in PRO as assessed by EuroQol-5D (EQ-5D-3L)		5 years post-drug product infusion
Change From Baseline in PRO as assessed by Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) Questionnaire Score		5 years post-drug product infusion
Change from Baseline in PRO as assessed by Short Form-36 Health Survey (SF-36)		5 years post-drug product infusion
Change in annualized pRBC transfusion volume (among subjects who achieved TI), from 6 months post-drug product infusion (parent study) through last follow-up	Reduction in annualized pRBC transfusion volume (mL/kg/year) from 6 months post-drug product infusion (parent study) through last follow-up of at least 50%, 60%, 75%, 90%, or 100% as compared to the annualized pRBC transfusion volume during the 2 years prior to parent study enrollment	Up to 15 years post-drug product infusion
Annualized pRBC transfusion volume, from 6 months post-drug product infusion (parent study) through last follow-up	Annualized pRBC transfusion volume (mL/kg/year from 6 months post-drug product infusion (parent study) through last follow-up as compared to the annualized pRBC transfusion requirements during the 2 years prior to parent study enrollment	Up to 15 years post-drug product infusion
pRBC transfusion frequency, from 6 months post-drug product infusion (parent study) through last follow-up	Annualized pRBC frequency (number/year) from 6 months post-drug product infusion (parent study) through last follow-up as compared to the annualized pRBC transfusion requirements during the 2 years prior to parent study enrollment	Up to 15 years post-drug product infusion

Collaborators and Investigators

• Sponsor: bluebird bio
• Investigators: Study Director: Himal L Thakar, MD, bluebird bio, Inc.

Publications and helpful links

General Publications

• 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.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2014
• Primary Completion (Estimated): November 1, 2035
• Study Completion (Estimated): November 1, 2035

Study Registration Dates

• First Submitted: November 30, 2015
• First Submitted That Met QC Criteria: December 15, 2015
• First Posted (Estimated): December 17, 2015

Study Record Updates

• Last Update Posted (Actual): March 26, 2024
• Last Update Submitted That Met QC Criteria: March 25, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Thalassemia; beta-Thalassemia
• Other Study ID Numbers: LTF-303

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Bluebird bio is committed to transparency and appropriately de-identified subject-level datasets and supporting documents may be shared after all participants have completed study participation and following attainment of applicable marketing approvals associated with a given study and consistent with criteria established by bluebird bio and/or industry best practices to maintain the privacy of study participants. For enquiries, please contact us at datasharing@bluebirdbio.com.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No