Study to Evaluate the Safety and Tolerability of Tirabrutinib (ONO/GS-4059) Given as Monotherapy in Participants With Relapsed/Refractory NHL and CLL

Chronic Lymphocytic Leukaemia Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01659255
• Other study ID #: ONO-4059POE001
• Secondary ID: 2011-005033-39
• Status: Completed
• Phase: Phase 1
• Start date: August 17, 2012
• Est. completion date: January 11, 2016

Study information

• Verified date: February 2021
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: January 11, 2016
• Est. primary completion date: February 23, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukaemia
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Lymphoma
• Lymphoma, Non-Hodgkin
• Non Hodgkins Lymphoma

Intervention

Drug:
• Tirabrutinib
Capsules administered orally

Locations

Country	Name	City	State
France	CHRU - Hopital Claude HURIEZ	Lille
France	Centre hospitalier Lyon Sud	Lyon
France	CHU St Eloi	Montpellier
United Kingdom	University Hospital of Wales	Cardiff
United Kingdom	Leicester Royal Infirmary	Leicester
United Kingdom	Derriford Hospital	Plymouth

Sponsors (2)

Lead Sponsor	Collaborator
Gilead Sciences	Ono Pharmaceutical Co. Ltd

Countries where clinical trial is conducted

France,  United Kingdom, 

References & Publications (4)

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 H

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.

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 — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Experiencing Dose-Limiting Toxicities	Dose Limiting Toxicities (DLT) were defined as follows: All Common Terminology Criteria (CTC) Grade 4 tirabrutinib related adverse events; All CTC Grade 3 tirabrutinib related adverse events, with the exception of the following: CTC Grade 3 lymphocytosis considered an expected outcome of therapy; Any toxicity which in the opinion of the Investigator is attributed to a participant's underlying disease was not considered a DLT.	Day 1 through Day 28
Secondary	Overall Response Rate	Overall response rate (ORR) was defined as the percentage of participants who achieve a best overall response of complete remission (CR, unconfirmed complete response (CRu), complete response with incomplete marrow recovery (CRi)) or partial remission (PR, nodal PR) during study as assessed by the investigator.; ORR assessment was defined per following standardized criteria: NHL: Cheson, 1999; CLL: International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008	Up to Cycle 37 (28 days for each cycle) plus 6-month intervals thereafter until disease progression (maximum: up to 39 months)
Secondary	Pharmacokinetic (PK) Parameter: Cmax of Tirabrutinib	Cmax is defined as the maximum concentration of drug.	Pre-dose, then 30 minutes, 1, 2, 3, 4, 6, 8, 12 hours post-dose at Cycle 1, Day 28
Secondary	PK Parameter: AUCtau of Tirabrutinib	AUCtau is defined as concentration of drug over dosing interval.	Pre-dose, then 30 minutes, 1, 2, 3, 4, 6, 8, 12 hours post-dose at Cycle 1, Day 28