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

Transfusion-dependent Beta-Thalassemia Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02633943
• Other study ID #: LTF-303
• Status: Active, not recruiting
• Start date: January 2014
• Est. completion date: November 2035

Study information

• Verified date: March 2024
• Source: bluebird bio
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical 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. 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 66
• Est. completion date: November 2035
• Est. primary completion date: November 2035
• Accepts healthy volunteers: No
• Gender: All
• Age group: 0 Years to 50 Years

Eligibility

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 ß-thalassemia in a bluebird bio-sponsored clinical study

Exclusion Criteria:

• There are no exclusion criteria for this study

Related Conditions & MeSH terms

• beta-Thalassemia
• Thalassemia
• Transfusion-dependent Beta-Thalassemia

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
bluebird bio

Countries where clinical trial is conducted

United States,  Australia,  France,  Germany,  Greece,  Italy,  Thailand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The number of subjects with malignancies		Up to 15 years post-drug product infusion
Primary	The number of subjects with immune-related AEs		Up to 15 years post-drug product infusion
Primary	The number of subjects with new or worsening hematologic disorders		Up to 15 years post-drug product infusion
Primary	The number of subjects with new or worsening neurologic disorders		Up to 15 years post-drug product infusion
Secondary	ßA-T87Q-globin expression	Median (min, max) ßA-T87Q-globin expression	Up to 15 years post-drug product infusion
Secondary	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
Secondary	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
Secondary	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
Secondary	Duration of Transfusion Independence		Up to 15 years post-drug product infusion
Secondary	Weighted average Hb during Transfusion Independence		Up to 15 years post-drug product infusion
Secondary	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
Secondary	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
Secondary	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
Secondary	Time from drug product infusion to last pRBC transfusion (in parent study or Study LTF-303)		Up to 15 years post-drug product infusion
Secondary	Time from last pRBC transfusion (in parent study or Study LTF-303) to last follow-up		Up to 15 years post-drug product infusion
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Cardiac T2* by MRI over time at yearly timepoints through last follow-up		Up to 15 years post-drug product infusion
Secondary	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
Secondary	Serum ferritin over time at yearly timepoints through last follow-up		Up to 15 years post-drug product infusion
Secondary	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
Secondary	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
Secondary	Number of subjects who stopped iron chelation for at least 6 months post-drug product infusion		Up to 15 years post-drug product infusion
Secondary	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
Secondary	Proportion of subjects using phlebotomy therapy post-drug product infusion		Up to 15 years post-drug product infusion
Secondary	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
Secondary	Reticulocyte counts over time at yearly timepoints through last follow-up		Up to 15 years post-drug product infusion
Secondary	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
Secondary	Proportion of subject with nucleated RBC over time at yearly timepoints through last follow-up		Up to 15 years post-drug product infusion
Secondary	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
Secondary	Change from Baseline in PRO as assessed by EuroQol-5D Youth version (EQ-5D-Y)		5 years post-drug product infusion
Secondary	Change from Baseline in PRO as assessed by EuroQol-5D (EQ-5D-3L)		5 years post-drug product infusion
Secondary	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
Secondary	Change from Baseline in PRO as assessed by Short Form-36 Health Survey (SF-36)		5 years post-drug product infusion

External Links

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