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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02633943




Registration number
NCT02633943
Ethics application status
Date submitted
30/11/2015
Date registered
17/12/2015
Date last updated
9/04/2025

Titles & IDs
Public title
Long-term Follow-up of Subjects With Transfusion-Dependent ß-Thalassemia (TDT) Treated With Ex Vivo Gene Therapy
Scientific title
Long-term Follow-up of Subjects With Transfusion-Dependent ß-Thalassemia (TDT) Treated With Ex Vivo Gene Therapy Using Autologous Hematopoietic Stem Cells Transduced With a Lentiviral Vector
Secondary ID [1] 0 0
LTF-303
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Transfusion-dependent Beta-Thalassemia 0 0
Condition category
Condition code
Blood 0 0 0 0
Haematological diseases
Blood 0 0 0 0
Other blood disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Observational
Patient registry
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Other interventions - Safety and efficacy assessments

Subjects with Transfusion-Dependent ß-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 interventions: Safety 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.
Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
The number of subjects with malignancies
Assessment method [1] 0 0
Timepoint [1] 0 0
Up to 15 years post-drug product infusion
Primary outcome [2] 0 0
The number of subjects with immune-related AEs
Assessment method [2] 0 0
Timepoint [2] 0 0
Up to 15 years post-drug product infusion
Primary outcome [3] 0 0
The number of subjects with new or worsening hematologic disorders
Assessment method [3] 0 0
Timepoint [3] 0 0
Up to 15 years post-drug product infusion
Primary outcome [4] 0 0
The number of subjects with new or worsening neurologic disorders
Assessment method [4] 0 0
Timepoint [4] 0 0
Up to 15 years post-drug product infusion
Secondary outcome [1] 0 0
ßA-T87Q-globin expression
Assessment method [1] 0 0
Median (min, max) ßA-T87Q-globin expression
Timepoint [1] 0 0
Up to 15 years post-drug product infusion
Secondary outcome [2] 0 0
Proportion of subjects treated with beti-cel who achieved Transfusion Independence (TI)
Assessment method [2] 0 0
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
Timepoint [2] 0 0
Up to 15 years post-drug product infusion
Secondary outcome [3] 0 0
Proportion of subjects treated with beti-cel who achieved Transfusion Independence at yearly timepoints
Assessment method [3] 0 0
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
Timepoint [3] 0 0
Up to 15 years post-drug product infusion
Secondary outcome [4] 0 0
Time from drug product infusion to achievement of Transfusion Independence (in parent study or Study LTF-303)
Assessment method [4] 0 0
Timepoint [4] 0 0
Up to 15 years post-drug product infusion
Secondary outcome [5] 0 0
Duration of Transfusion Independence
Assessment method [5] 0 0
Timepoint [5] 0 0
Up to 15 years post-drug product infusion
Secondary outcome [6] 0 0
Weighted average Hb during Transfusion Independence
Assessment method [6] 0 0
Timepoint [6] 0 0
Up to 15 years post-drug product infusion
Secondary outcome [7] 0 0
Change in annualized pRBC transfusion volume (among subjects who achieved TI), from 6 months post-drug product infusion (parent study) through last follow-up
Assessment method [7] 0 0
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
Timepoint [7] 0 0
Up to 15 years post-drug product infusion
Secondary outcome [8] 0 0
Annualized pRBC transfusion volume, from 6 months post-drug product infusion (parent study) through last follow-up
Assessment method [8] 0 0
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
Timepoint [8] 0 0
Up to 15 years post-drug product infusion
Secondary outcome [9] 0 0
pRBC transfusion frequency, from 6 months post-drug product infusion (parent study) through last follow-up
Assessment method [9] 0 0
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
Timepoint [9] 0 0
Up to 15 years post-drug product infusion
Secondary outcome [10] 0 0
Time from drug product infusion to last pRBC transfusion (in parent study or Study LTF-303)
Assessment method [10] 0 0
Timepoint [10] 0 0
Up to 15 years post-drug product infusion
Secondary outcome [11] 0 0
Time from last pRBC transfusion (in parent study or Study LTF-303) to last follow-up
Assessment method [11] 0 0
Timepoint [11] 0 0
Up to 15 years post-drug product infusion
Secondary outcome [12] 0 0
Weighted average nadir Hb from 6 months post-drug product infusion (parent study) through last follow-up
Assessment method [12] 0 0
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
Timepoint [12] 0 0
Up to 15 years post-drug product infusion
Secondary outcome [13] 0 0
Unsupported total Hb levels over time through last follow-up
Assessment method [13] 0 0
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.
Timepoint [13] 0 0
Up to 15 years post-drug product infusion
Secondary outcome [14] 0 0
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
Assessment method [14] 0 0
Timepoint [14] 0 0
Up to 15 years post-drug product infusion
Secondary outcome [15] 0 0
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
Assessment method [15] 0 0
Timepoint [15] 0 0
Up to 15 years post-drug product infusion
Secondary outcome [16] 0 0
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
Assessment method [16] 0 0
Timepoint [16] 0 0
Up to 15 years post-drug product infusion
Secondary outcome [17] 0 0
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
Assessment method [17] 0 0
Timepoint [17] 0 0
Up to 15 years post-drug product infusion
Secondary outcome [18] 0 0
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
Assessment method [18] 0 0
Timepoint [18] 0 0
Up to 15 years post-drug product infusion
Secondary outcome [19] 0 0
Liver iron content (LIC) by magnetic resonance imaging (MRI)/Superconducting Quantum Interference Device (SQUID) over time at yearly timepoints through last follow-up
Assessment method [19] 0 0
Timepoint [19] 0 0
Up to 15 years post-drug product infusion
Secondary outcome [20] 0 0
Change from parent study baseline in LIC by MRI/SQUID over time at yearly timepoints through last follow-up
Assessment method [20] 0 0
Timepoint [20] 0 0
Up to 15 years post-drug product infusion
Secondary outcome [21] 0 0
Cardiac T2* by MRI over time at yearly timepoints through last follow-up
Assessment method [21] 0 0
Timepoint [21] 0 0
Up to 15 years post-drug product infusion
Secondary outcome [22] 0 0
Change from parent study baseline in cardiac T2* by MRI over time at yearly timepoints through last follow-up
Assessment method [22] 0 0
Timepoint [22] 0 0
Up to 15 years post-drug product infusion
Secondary outcome [23] 0 0
Serum ferritin over time at yearly timepoints through last follow-up
Assessment method [23] 0 0
Timepoint [23] 0 0
Up to 15 years post-drug product infusion
Secondary outcome [24] 0 0
Change from parent study baseline in serum ferritin over time at yearly timepoints through last follow-up
Assessment method [24] 0 0
Timepoint [24] 0 0
Up to 15 years post-drug product infusion
Secondary outcome [25] 0 0
Number of subjects who stopped iron chelation post-DP infusion
Assessment method [25] 0 0
Defined as subjects who stopped iron chelation or never restarted chelation after DP infusion.
Timepoint [25] 0 0
Up to 15 years post-drug product infusion
Secondary outcome [26] 0 0
Number of subjects who stopped iron chelation for at least 6 months post-drug product infusion
Assessment method [26] 0 0
Timepoint [26] 0 0
Up to 15 years post-drug product infusion
Secondary outcome [27] 0 0
Time from stopping chelation to last follow-up
Assessment method [27] 0 0
Among subjects that never restart chelation after DP infusion.
Timepoint [27] 0 0
Up to 15 years post-drug product infusion
Secondary outcome [28] 0 0
Proportion of subjects using phlebotomy therapy post-drug product infusion
Assessment method [28] 0 0
Timepoint [28] 0 0
Up to 15 years post-drug product infusion
Secondary outcome [29] 0 0
Annualized frequency of phlebotomy therapy usage
Assessment method [29] 0 0
Annualized frequency of phlebotomy therapy usage is defined as the number of procedures per year, calculated from DP infusion through last follow-up.
Timepoint [29] 0 0
Up to 15 years post-drug product infusion
Secondary outcome [30] 0 0
Reticulocyte counts over time at yearly timepoints through last follow-up
Assessment method [30] 0 0
Timepoint [30] 0 0
Up to 15 years post-drug product infusion
Secondary outcome [31] 0 0
Change from Baseline in reticulocyte counts at yearly timepoints through last follow-up
Assessment method [31] 0 0
Baseline defined as value closest, but prior to, conditioning in parent study.
Timepoint [31] 0 0
15 years post-drug product infusion
Secondary outcome [32] 0 0
Proportion of subject with nucleated RBC over time at yearly timepoints through last follow-up
Assessment method [32] 0 0
Timepoint [32] 0 0
Up to 15 years post-drug product infusion
Secondary outcome [33] 0 0
Change from Baseline in patient reported outcome (PRO) as assessed by Pediatric Quality of Life Inventory (PedsQL
Assessment method [33] 0 0
Timepoint [33] 0 0
5 years post-drug product infusion
Secondary outcome [34] 0 0
Change from Baseline in PRO as assessed by EuroQol-5D Youth version (EQ-5D-Y)
Assessment method [34] 0 0
Timepoint [34] 0 0
5 years post-drug product infusion
Secondary outcome [35] 0 0
Change from Baseline in PRO as assessed by EuroQol-5D (EQ-5D-3L)
Assessment method [35] 0 0
Timepoint [35] 0 0
5 years post-drug product infusion
Secondary outcome [36] 0 0
Change From Baseline in PRO as assessed by Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) Questionnaire Score
Assessment method [36] 0 0
Timepoint [36] 0 0
5 years post-drug product infusion
Secondary outcome [37] 0 0
Change from Baseline in PRO as assessed by Short Form-36 Health Survey (SF-36)
Assessment method [37] 0 0
Timepoint [37] 0 0
5 years post-drug product infusion

Eligibility
Key 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
Minimum age
0 Years
Maximum age
50 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* There are no exclusion criteria for this study

Study design
Purpose
Duration
Selection
Timing
Prospective
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/01/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/11/2035
Actual
Sample size
Target
Accrual to date
Final
66
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
- Sydney
Recruitment postcode(s) [1] 0 0
- Sydney
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Illinois
Country [3] 0 0
United States of America
State/province [3] 0 0
Maryland
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
United States of America
State/province [5] 0 0
Pennsylvania
Country [6] 0 0
United States of America
State/province [6] 0 0
South Carolina
Country [7] 0 0
France
State/province [7] 0 0
Marseille
Country [8] 0 0
France
State/province [8] 0 0
Paris
Country [9] 0 0
Germany
State/province [9] 0 0
Hannover
Country [10] 0 0
Germany
State/province [10] 0 0
Heidelberg
Country [11] 0 0
Greece
State/province [11] 0 0
Thessaloníki
Country [12] 0 0
Italy
State/province [12] 0 0
Rome
Country [13] 0 0
Thailand
State/province [13] 0 0
Bangkok
Country [14] 0 0
United Kingdom
State/province [14] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
bluebird bio
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Himal L Thakar, MD
Address 0 0
bluebird bio, Inc.
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT02633943