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

Active, not recruiting

• Conditions: Transfusion-dependent Beta-Thalassemia
• Interventions: Other: Safety and efficacy assessments

• Registration Number: NCT02633943
• Lead Sponsor: bluebird bio

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 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.

Detailed Description

Not available

Study Timeline

• Study Start: 2014-01
• Study First Submitted: 2015-11-30
• Study First Submitted QC: 2015-12-15
• Study First Posted: 2015-12-17
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-25
• Last Update Posted: 2024-03-26
• Primary Completion: 2035-11
• Study Completion: 2035-11

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 66

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

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Exclusion Criteria

• There are no exclusion criteria for this study

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Subjects with Transfusion-Dependent β-Thalassemia	Safety and efficacy assessments	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)

Primary Outcome Measures

Name	Time	Method
The number of subjects with new or worsening hematologic disorders	Up to 15 years post-drug product infusion
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 neurologic disorders	Up to 15 years post-drug product infusion

Secondary Outcome Measures

Name	Time	Method
Weighted average Hb during Transfusion Independence	Up to 15 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	Up to 15 years post-drug product infusion	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
Proportion of subjects treated with beti-cel who achieved Transfusion Independence (TI)	Up to 15 years post-drug product infusion	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
Annualized pRBC transfusion volume, from 6 months post-drug product infusion (parent study) through last follow-up	Up to 15 years post-drug product infusion	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
pRBC transfusion frequency, from 6 months post-drug product infusion (parent study) through last follow-up	Up to 15 years post-drug product infusion	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
Duration of Transfusion Independence	Up to 15 years post-drug product infusion
βA-T87Q-globin expression	Up to 15 years post-drug product infusion	Median (min, max) βA-T87Q-globin expression
Time from last pRBC transfusion (in parent study or Study LTF-303) to last follow-up	Up to 15 years post-drug product infusion
Unsupported total Hb levels over time through last follow-up	Up to 15 years post-drug product infusion	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.
Proportion of subjects treated with beti-cel who achieved Transfusion Independence at yearly timepoints	Up to 15 years post-drug product infusion	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 from drug product infusion to achievement of Transfusion Independence (in parent study or Study LTF-303)	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
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
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
Time from stopping chelation to last follow-up	Up to 15 years post-drug product infusion	Among subjects that never restart chelation after DP infusion.
Change from Baseline in reticulocyte counts at yearly timepoints through last follow-up	15 years post-drug product infusion	Baseline defined as value closest, but prior to, conditioning in parent study.
Proportion of subject with nucleated RBC over time at yearly timepoints through 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	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 as compared to the weighted average nadir Hb during the 2 years prior to parent study enrollment
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 ≥ 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
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
Number of subjects who stopped iron chelation post-DP infusion	Up to 15 years post-drug product infusion	Defined as subjects who stopped iron chelation or never restarted chelation after DP infusion.
Reticulocyte counts over time at yearly timepoints through last follow-up	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
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
Number of subjects who stopped iron chelation for at least 6 months post-drug product 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	Up to 15 years post-drug product infusion	Annualized frequency of phlebotomy therapy usage is defined as the number of procedures per year, calculated from DP infusion through last follow-up.
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 (EQ-5D-3L)	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 Short Form-36 Health Survey (SF-36)	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