Clinical trial NCT01659255: Study to Evaluate the Safety and Tolerability of Tirabrutinib (ONO/GS-4059) Given as Monotherapy in Participants With Relapsed/Refractory NHL and CLL
Official title: An Open-label, Multi-Center, Non-Randomised Phase I Dose-Escalation Study to Investigate the Safety and Tolerability of ONO-4059 (ONO/GS-4059) Given as Monotherapy in Patients With Relapsed/Refractory Non-Hodgkin's Lymphoma (NHL) and Relapsed/Refractory Chronic Lymphocytic Leukaemia (CLL)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Non Hodgkins Lymphoma
Chronic Lymphocytic Leukaemia
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
Collaborators: name: Ono Pharmaceutical Co. Ltd
First posted: 2012-08-07
Enrollment: 90
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 the study is to evaluate the safety and tolerability of tirabrutinib (formerly ONO/GS-4059) given as monotherapy to participants with relapsed/refractory non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL).


Eligibility criteria: Key Inclusion Criteria:

1. Males or females with a confirmed diagnosis of and documented history of relapsed or refractory malignant disease (B-cell lymphoma and/or CLL) for which no therapy of curative or high priority exists and for whom treatment with a Btk inhibitor may be deemed appropriate.
2. Age ≥ 18 years.
3. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.

Key Exclusion Criteria:

1. Central nervous system (CNS) lymphoma.
2. Women who are pregnant or lactating.

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

Primary outcomes:
measure: Percentage of Participants Experiencing Dose-Limiting Toxicities
timeFrame: Day 1 through Day 28
Secondary outcomes:
measure: Overall Response Rate
timeFrame: Up to Cycle 37 (28 days for each cycle) plus 6-month intervals thereafter until disease progression (maximum: up to 39 months)
measure: Pharmacokinetic (PK) Parameter: Cmax of Tirabrutinib
timeFrame: Pre-dose, then 30 minutes, 1, 2, 3, 4, 6, 8, 12 hours post-dose at Cycle 1, Day 28
measure: PK Parameter: AUCtau of Tirabrutinib
timeFrame: Pre-dose, then 30 minutes, 1, 2, 3, 4, 6, 8, 12 hours post-dose at Cycle 1, Day 28
Other outcomes:
Locations:
city: Lille
country: France
facility: CHRU - Hopital Claude HURIEZ
city: Lyon
country: France
facility: Centre hospitalier Lyon Sud
city: Montpellier
country: France
facility: CHU St Eloi
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: 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.
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: Fegan, C, Bagshawe J, Salles G, et al. The Bruton's tyrosine kinase (BTK) inhibitor ONO-4059: promising single agent activity and well tolerated in patients with high risk chronic lymphocytic leukaemia (CLL). Paper presented at: 56th American Society of Hematology Annual Meeting and Exposition; December 6-9, 2014; San Franscisco, CA.
citation: Morschhauser F, Terriou L, Dyer M, et al. The Bruton's tyrosine kinase (BTK) inhibitor ONO-4059: promising single agent activity in patients with relapsed and refractory NHL. Haematologica. 2014 Jun; 99: 150.