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

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• Thalassemia 416
• beta-Thalassemia 305

Thalassemia

416 studies on the registry are indexed under Thalassemia; 67 are open to participants now.

This study's enrollment of 66 is below the median of 100 across 120 observational studies indexed under Thalassemia.

Lead sponsor

bluebird bio is the lead sponsor of 12 studies on the registry; 2 are open to participants now.

Study population

Groups and cohorts

• 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

• OtherSafety and efficacy assessments

  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.

Primary outcomes

1. The number of subjects with malignancies

   Time frame: Up to 15 years post-drug product infusion

2. The number of subjects with immune-related AEs

   Time frame: Up to 15 years post-drug product infusion

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

   Time frame: Up to 15 years post-drug product infusion

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

   Time frame: Up to 15 years post-drug product infusion

Secondary outcomes

1. βA-T87Q-globin expression

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

   Time frame: 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

   Time frame: 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

   Time frame: 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)

   Time frame: Up to 15 years post-drug product infusion

5. Duration of Transfusion Independence

   Time frame: Up to 15 years post-drug product infusion

6. Weighted average Hb during Transfusion Independence

   Time frame: 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

   Time frame: 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

   Time frame: 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

   Time frame: 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)

    Time frame: 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

    Time frame: 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

    Time frame: 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.

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: Up to 15 years post-drug product infusion

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

    Time frame: 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

    Time frame: Up to 15 years post-drug product infusion

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

    Time frame: 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

    Time frame: 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.

    Time frame: 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

    Time frame: 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.

    Time frame: Up to 15 years post-drug product infusion

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

    Time frame: 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.

    Time frame: Up to 15 years post-drug product infusion

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

    Time frame: 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.

    Time frame: 15 years post-drug product infusion

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

    Time frame: 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

    Time frame: 5 years post-drug product infusion

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

    Time frame: 5 years post-drug product infusion

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

    Time frame: 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

    Time frame: 5 years post-drug product infusion

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

    Time frame: 5 years post-drug product infusion

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. PubMed 35075288 ↗

Related links

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

Individual participant data

Plan to share: 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.