Clinical trial NCT02633943: Long-term Follow-up of Subjects With Transfusion-Dependent β-Thalassemia (TDT) Treated With Ex Vivo Gene Therapy
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
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Transfusion-dependent Beta-Thalassemia
Lead sponsor: bluebird bio
Sponsor class: INDUSTRY
First posted: 2015-12-17
Enrollment: 66
Sex: ALL
Minimum age (years): 0
Maximum age (years): 50
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Subjects with transfusion-dependent β-thalassemia who have been treated with ex vivo gene therapy product in bluebird bio-sponsored clinical studies

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 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.


Eligibility criteria: 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

Exclusion Criteria:

* There are no exclusion criteria for this study

Primary outcomes:
measure: The number of subjects with malignancies
timeFrame: Up to 15 years post-drug product infusion
measure: The number of subjects with immune-related AEs
timeFrame: Up to 15 years post-drug product infusion
measure: The number of subjects with new or worsening hematologic disorders
timeFrame: Up to 15 years post-drug product infusion
measure: The number of subjects with new or worsening neurologic disorders
timeFrame: Up to 15 years post-drug product infusion
Secondary outcomes:
measure: βA-T87Q-globin expression
timeFrame: Up to 15 years post-drug product infusion
measure: Proportion of subjects treated with beti-cel who achieved Transfusion Independence (TI)
timeFrame: Up to 15 years post-drug product infusion
measure: Proportion of subjects treated with beti-cel who achieved Transfusion Independence at yearly timepoints
timeFrame: Up to 15 years post-drug product infusion
measure: Time from drug product infusion to achievement of Transfusion Independence (in parent study or Study LTF-303)
timeFrame: Up to 15 years post-drug product infusion
measure: Duration of Transfusion Independence
timeFrame: Up to 15 years post-drug product infusion
measure: Weighted average Hb during Transfusion Independence
timeFrame: Up to 15 years post-drug product infusion
measure: Change in annualized pRBC transfusion volume (among subjects who achieved TI), from 6 months post-drug product infusion (parent study) through last follow-up
timeFrame: Up to 15 years post-drug product infusion
measure: Annualized pRBC transfusion volume, from 6 months post-drug product infusion (parent study) through last follow-up
timeFrame: Up to 15 years post-drug product infusion
measure: pRBC transfusion frequency, from 6 months post-drug product infusion (parent study) through last follow-up
timeFrame: Up to 15 years post-drug product infusion
measure: Time from drug product infusion to last pRBC transfusion (in parent study or Study LTF-303)
timeFrame: Up to 15 years post-drug product infusion
measure: Time from last pRBC transfusion (in parent study or Study LTF-303) to last follow-up
timeFrame: Up to 15 years post-drug product infusion
measure: Weighted average nadir Hb from 6 months post-drug product infusion (parent study) through last follow-up
timeFrame: Up to 15 years post-drug product infusion
measure: Unsupported total Hb levels over time through last follow-up
timeFrame: Up to 15 years post-drug product infusion
measure: 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
timeFrame: Up to 15 years post-drug product infusion
measure: 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
timeFrame: Up to 15 years post-drug product infusion
measure: 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
timeFrame: Up to 15 years post-drug product infusion
measure: 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
timeFrame: Up to 15 years post-drug product infusion
measure: 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
timeFrame: Up to 15 years post-drug product infusion
measure: Liver iron content (LIC) by magnetic resonance imaging (MRI)/Superconducting Quantum Interference Device (SQUID) over time at yearly timepoints through last follow-up
timeFrame: Up to 15 years post-drug product infusion
measure: Change from parent study baseline in LIC by MRI/SQUID over time at yearly timepoints through last follow-up
timeFrame: Up to 15 years post-drug product infusion
measure: Cardiac T2* by MRI over time at yearly timepoints through last follow-up
timeFrame: Up to 15 years post-drug product infusion
measure: Change from parent study baseline in cardiac T2* by MRI over time at yearly timepoints through last follow-up
timeFrame: Up to 15 years post-drug product infusion
measure: Serum ferritin over time at yearly timepoints through last follow-up
timeFrame: Up to 15 years post-drug product infusion
measure: Change from parent study baseline in serum ferritin over time at yearly timepoints through last follow-up
timeFrame: Up to 15 years post-drug product infusion
measure: Number of subjects who stopped iron chelation post-DP infusion
timeFrame: Up to 15 years post-drug product infusion
measure: Number of subjects who stopped iron chelation for at least 6 months post-drug product infusion
timeFrame: Up to 15 years post-drug product infusion
measure: Time from stopping chelation to last follow-up
timeFrame: Up to 15 years post-drug product infusion
measure: Proportion of subjects using phlebotomy therapy post-drug product infusion
timeFrame: Up to 15 years post-drug product infusion
measure: Annualized frequency of phlebotomy therapy usage
timeFrame: Up to 15 years post-drug product infusion
measure: Reticulocyte counts over time at yearly timepoints through last follow-up
timeFrame: Up to 15 years post-drug product infusion
measure: Change from Baseline in reticulocyte counts at yearly timepoints through last follow-up
timeFrame: 15 years post-drug product infusion
measure: Proportion of subject with nucleated RBC over time at yearly timepoints through last follow-up
timeFrame: Up to 15 years post-drug product infusion
measure: Change from Baseline in patient reported outcome (PRO) as assessed by Pediatric Quality of Life Inventory (PedsQL
timeFrame: 5 years post-drug product infusion
measure: Change from Baseline in PRO as assessed by EuroQol-5D Youth version (EQ-5D-Y)
timeFrame: 5 years post-drug product infusion
measure: Change from Baseline in PRO as assessed by EuroQol-5D (EQ-5D-3L)
timeFrame: 5 years post-drug product infusion
measure: Change From Baseline in PRO as assessed by Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) Questionnaire Score
timeFrame: 5 years post-drug product infusion
measure: Change from Baseline in PRO as assessed by Short Form-36 Health Survey (SF-36)
timeFrame: 5 years post-drug product infusion
Other outcomes:
Locations:
city: Oakland
country: United States
state: California
city: Chicago
country: United States
state: Illinois
city: Bethesda
country: United States
state: Maryland
city: New York
country: United States
state: New York
city: Philadelphia
country: United States
state: Pennsylvania
city: Charleston
country: United States
state: South Carolina
city: Sydney
country: Australia
city: Marseille
country: France
city: Paris
country: France
city: Hannover
country: Germany
city: Heidelberg
country: Germany
city: Thessaloníki
country: Greece
city: Rome
country: Italy
city: Bangkok
country: Thailand
city: London
country: United Kingdom
Study officials:
affiliation: bluebird bio, Inc.
name: Himal L Thakar, MD
role: STUDY_DIRECTOR
References:
citation: 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.