Clinical trial NCT02457559: Study to Assess the Long-term Safety and Efficacy of Tirabrutinib in Adults With Relapsed/Refractory B-cell Malignancies
Official title: An Open-label Study to Assess the Long-term Safety and Efficacy of ONO/GS-4059 in Subjects With Relapsed/Refractory B-cell Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Relapsed/Refractory B-cell Malignancies
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2015-05-29
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to determine the long-term safety and tolerability of tirabrutinib in adults with relapsed/refractory B-cell malignancy who have tolerated and achieved stable disease or improved with tirabrutinib treatment while enrolled in a prior (parent study) tirabrutinib study (NCT01659255). The dosing regimen will be based on the prior dosing regimen from the parent study.


Eligibility criteria: Key Inclusion Criteria:

* Currently enrolled in a prior tirabrutinib study
* Did not discontinue treatment with tirabrutinib for any reason other than to enroll in this study
* Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 at enrollment in this study
* Any Grade 3 or 4 non-hematologic toxicity that the investigator considers related to previous tirabrutinib use must have resolved, reverted to Grade 1, or reverted to the baseline of the prior study prior to Day 1 of this study
* Negative serum and urine pregnancy test is required for female individuals (unless surgically sterile or greater than 2 years post menopausal)
* Male and female individuals of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception as described in the protocol
* Lactating females must agree to discontinue nursing before the study drug is administered
* Ability and agreement to attend protocol-specified visits at the study site
* Able to comprehend and willing to sign the informed consent form

Key Exclusion Criteria:

* Known hypersensitivity to tirabrutinib, its metabolites, or formulation excipients

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (AEs)
timeFrame: First dose of tirabrutinib up to 36 months in the parent study and up to 61 months in the rollover study
measure: Percentage of Participants Who Experienced Treatment-Emergent Marked Laboratory Abnormalities
timeFrame: First dose of tirabrutinib up to 36 months in the parent study and up to 61 months in the rollover study
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Up to 39 months in parent study and up to 60 months in rollover study
measure: Duration of Response (DOR)
timeFrame: From first documentation of CR or PR to the first documentation of disease progression or death from any cause up to 39 months in parent study and up to 60 months in the rollover study
measure: Progression-free Survival (PFS)
timeFrame: From first dose of tirabrutinib in the parent study (NCT01659255) to the first documentation of disease progression or death from any cause up to 99 months
measure: Overall Survival (OS)
timeFrame: From first dose of tirabrutinib in the parent study (NCT01659255) until death from any cause up to 99 months
Other outcomes:
Locations:
city: Lille
country: France
facility: CHRU de Lille
state: Nord
city: Montpellier
country: France
facility: Hopital Saint Eloi
city: Pierre Benite
country: France
facility: Centre Hospitalier Lyon Sud
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: Yu H, Truong H, Mitchell SA, Liclican A, Gosink JJ, Li W, Lin J, Feng JY, Jurgensmeier JM, Billin A, Xu R, Patterson S, Pagratis N. Homogeneous BTK Occupancy Assay for Pharmacodynamic Assessment of Tirabrutinib (GS-4059/ONO-4059) Target Engagement. SLAS Discov. 2018 Oct;23(9):919-929. doi: 10.1177/2472555218786165. Epub 2018 Jul 16.
citation: Rule SA, Cartron G, Fegan C, Morschhauser F, Han L, Mitra S, Salles G, Dyer MJS. Long-term follow-up of patients with mantle cell lymphoma (MCL) treated with the selective Bruton's tyrosine kinase inhibitor tirabrutinib (GS/ONO-4059). Leukemia. 2020 May;34(5):1458-1461. doi: 10.1038/s41375-019-0658-7. Epub 2019 Dec 11. No abstract available.
citation: Walter HS, Jayne S, Rule SA, Cartron G, Morschhauser F, Macip S, Karlin L, Jones C, Herbaux C, Quittet P, Shah N, Hutchinson CV, Fegan C, Yang Y, Mitra S, Salles G, Dyer MJS. Long-term follow-up of patients with CLL treated with the selective Bruton's tyrosine kinase inhibitor ONO/GS-4059. Blood. 2017 May 18;129(20):2808-2810. doi: 10.1182/blood-2017-02-765115. Epub 2017 Apr 4. No abstract available.
citation: Walter HS, Rule SA, Dyer MJ, Karlin L, Jones C, Cazin B, Quittet P, Shah N, Hutchinson CV, Honda H, Duffy K, Birkett J, Jamieson V, Courtenay-Luck N, Yoshizawa T, Sharpe J, Ohno T, Abe S, Nishimura A, Cartron G, Morschhauser F, Fegan C, Salles G. A phase 1 clinical trial of the selective BTK inhibitor ONO/GS-4059 in relapsed and refractory mature B-cell malignancies. Blood. 2016 Jan 28;127(4):411-9. doi: 10.1182/blood-2015-08-664086. Epub 2015 Nov 5.
citation: Walter HS, Salles GA, Dyer MJ. New Agents to Treat Chronic Lymphocytic Leukemia. N Engl J Med. 2016 Jun 2;374(22):2185-6. doi: 10.1056/NEJMc1602674. No abstract available.