AzTrials
AzTrials

Transfusion-dependent Beta-ThalassemiaNCT02633943

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

An observational study of Transfusion-dependent Beta-Thalassemia, run by Genetix Biotherapeutics Inc. at 15 sites in 8 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 0 to 50 years
Conditions the study is for
Transfusion-dependent Beta-Thalassemia
What is being tested?
Safety and efficacy assessments
Type of treatment
Injection or infusion
How many people
66 participants
Where
15 sitesin 8 countries
Study dates
Jan 2014to Nov 2035
Phase
Observational
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 0 to 50 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

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

Who may be able to join

  • 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

Who cannot join

  • There are no exclusion criteria for this study

Trial locations and contacts

15 sites in 8 countries.

15 sites in 8 countries

United States6 sites
  • Study site

    Bethesda, Maryland

  • Study site

    Charleston, South Carolina

  • Study site

    Chicago, Illinois

  • Study site

    New York, New York

  • Study site

    Oakland, California

  • Study site

    Philadelphia, Pennsylvania

Other trials in United States

France2 sites
  • Study site

    Marseille

  • Study site

    Paris

Other trials in France

Germany2 sites
  • Study site

    Hanover

  • Study site

    Heidelberg

Other trials in Germany

Australia1 site
  • Study site

    Sydney

Other trials in Australia

Greece1 site
  • Study site

    Thessaloniki

Other trials in Greece

Italy1 site
  • Study site

    Rome

Other trials in Italy

Thailand1 site
  • Study site

    Bangkok

Other trials in Thailand

United Kingdom1 site
  • Study site

    London

Other trials in United Kingdom

About this study

Official title: 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 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.

Being tested
Safety and efficacy assessments

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Safety and efficacy assessmentsOther

    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.

Study groups in NCT02633943
Study groupRoleWhat they receive
Subjects with Transfusion-Dependent β-ThalassemiaLong-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)
Receives: Other: Safety and efficacy assessments

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The number of subjects with malignancies

    Measured: Up to 15 years post-drug product infusion

  2. The number of subjects with immune-related AEs

    Measured: Up to 15 years post-drug product infusion

  3. The number of subjects with new or worsening hematologic disorders

    Measured: Up to 15 years post-drug product infusion

  4. The number of subjects with new or worsening neurologic disorders

    Measured: Up to 15 years post-drug product infusion

Secondary outcomes (37)
  1. βA-T87Q-globin expression

    Median (min, max) βA-T87Q-globin expression

    Measured: Up to 15 years post-drug product infusion

  2. 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

    Measured: Up to 15 years post-drug product infusion

  3. 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

    Measured: Up to 15 years post-drug product infusion

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

    Measured: Up to 15 years post-drug product infusion

  5. Duration of Transfusion Independence

    Measured: Up to 15 years post-drug product infusion

  6. Weighted average Hb during Transfusion Independence

    Measured: Up to 15 years post-drug product infusion

  7. 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

    Measured: Up to 15 years post-drug product infusion

  8. 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

    Measured: Up to 15 years post-drug product infusion

  9. 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

    Measured: Up to 15 years post-drug product infusion

  10. Time from drug product infusion to last pRBC transfusion (in parent study or Study LTF-303)

    Measured: Up to 15 years post-drug product infusion

  11. Time from last pRBC transfusion (in parent study or Study LTF-303) to last follow-up

    Measured: Up to 15 years post-drug product infusion

  12. 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

    Measured: Up to 15 years post-drug product infusion

  13. 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.

    Measured: Up to 15 years post-drug product infusion

  14. 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

    Measured: Up to 15 years post-drug product infusion

  15. 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

    Measured: Up to 15 years post-drug product infusion

  16. 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

    Measured: Up to 15 years post-drug product infusion

  17. 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

    Measured: Up to 15 years post-drug product infusion

  18. 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

    Measured: Up to 15 years post-drug product infusion

  19. Liver iron content (LIC) by magnetic resonance imaging (MRI)/Superconducting Quantum Interference Device (SQUID) over time at yearly timepoints through last follow-up

    Measured: Up to 15 years post-drug product infusion

  20. Change from parent study baseline in LIC by MRI/SQUID over time at yearly timepoints through last follow-up

    Measured: Up to 15 years post-drug product infusion

  21. Cardiac T2* by MRI over time at yearly timepoints through last follow-up

    Measured: Up to 15 years post-drug product infusion

  22. Change from parent study baseline in cardiac T2* by MRI over time at yearly timepoints through last follow-up

    Measured: Up to 15 years post-drug product infusion

  23. Serum ferritin over time at yearly timepoints through last follow-up

    Measured: Up to 15 years post-drug product infusion

  24. Change from parent study baseline in serum ferritin over time at yearly timepoints through last follow-up

    Measured: Up to 15 years post-drug product infusion

  25. Number of subjects who stopped iron chelation post-DP infusion

    Defined as subjects who stopped iron chelation or never restarted chelation after DP infusion.

    Measured: Up to 15 years post-drug product infusion

  26. Number of subjects who stopped iron chelation for at least 6 months post-drug product infusion

    Measured: Up to 15 years post-drug product infusion

  27. Time from stopping chelation to last follow-up

    Among subjects that never restart chelation after DP infusion.

    Measured: Up to 15 years post-drug product infusion

  28. Proportion of subjects using phlebotomy therapy post-drug product infusion

    Measured: Up to 15 years post-drug product infusion

  29. 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.

    Measured: Up to 15 years post-drug product infusion

  30. Reticulocyte counts over time at yearly timepoints through last follow-up

    Measured: Up to 15 years post-drug product infusion

  31. 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.

    Measured: 15 years post-drug product infusion

  32. Proportion of subject with nucleated RBC over time at yearly timepoints through last follow-up

    Measured: Up to 15 years post-drug product infusion

  33. Change from Baseline in patient reported outcome (PRO) as assessed by Pediatric Quality of Life Inventory (PedsQL

    Measured: 5 years post-drug product infusion

  34. Change from Baseline in PRO as assessed by EuroQol-5D Youth version (EQ-5D-Y)

    Measured: 5 years post-drug product infusion

  35. Change from Baseline in PRO as assessed by EuroQol-5D (EQ-5D-3L)

    Measured: 5 years post-drug product infusion

  36. Change From Baseline in PRO as assessed by Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) Questionnaire Score

    Measured: 5 years post-drug product infusion

  37. Change from Baseline in PRO as assessed by Short Form-36 Health Survey (SF-36)

    Measured: 5 years post-drug product infusion

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Dec 2015 (estimated)
  2. Study startJan 2014
  3. Primary completionNov 2035 (estimated)
  4. Study completionNov 2035 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Case only
Time perspective
Prospective
Enrolment
66 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02633943
Sponsor's protocol ID
LTF-303
Status last verified
Apr 2025
First submitted
30 Nov 2015
Last updated
9 Apr 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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.

Publications

  • 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 JEJ, Kunz JB, Kinney MA, Chawla A, Ali S, Tao G, Thakar HL, 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 May 7;147(19):2203-2214. doi: 10.1182/blood.2025029196.

    PubMed 41525466
  • 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.

    PubMed 39527960
  • 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.

    PubMed 35075288

Questions about this trial

What is this clinical trial studying?

An observational study of Transfusion-dependent Beta-Thalassemia, run by Genetix Biotherapeutics Inc. at 15 sites in 8 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 9 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in United States, France, Germany, Australia, Greece and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The number of subjects with malignancies (time frame: Up to 15 years post-drug product infusion). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02633943, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Apr 2025.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in