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

Phase 1

Completed

• Conditions: Non Hodgkins Lymphoma; Chronic Lymphocytic Leukaemia
• Interventions: Drug: Tirabrutinib

• Registration Number: NCT01659255
• Lead Sponsor: Gilead Sciences

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2012-07-06
• Study First Submitted QC: 2012-08-06
• Study First Posted: 2012-08-07
• Study Start: 2012-08-17
• Primary Completion: 2015-02-23
• Study Completion: 2016-01-11
• Results First Submitted: 2021-01-06
• Results First Submitted QC: 2021-01-06
• Results First Posted: 2021-01-28
• Status Verified: 2021-02
• Last Update Submitted: 2021-02-22
• Last Update Posted: 2021-03-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 90

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Tirabrutinib 40 mg Once Daily (NHL)	Tirabrutinib	Participants with relapsed/refractory NHL received tirabrutinib 40 mg once daily.
Tirabrutinib 20 mg Once Daily (CLL)	Tirabrutinib	Participants with relapsed/refractory chronic lymphocytic leukaemia (CLL) received tirabrutinib 20 mg once daily.
Tirabrutinib 160 mg Once Daily (CLL)	Tirabrutinib	Participants with relapsed/refractory CLL received tirabrutinib 160 mg once daily.
Tirabrutinib 400 mg Once Daily (CLL)	Tirabrutinib	Participants with relapsed/refractory CLL received tirabrutinib 400 mg once daily.
Tirabrutinib 500 mg Once Daily (CLL)	Tirabrutinib	Participants with relapsed/refractory CLL received tirabrutinib 500 mg once daily.
Tirabrutinib 600 mg Once Daily (CLL)	Tirabrutinib	Participants with relapsed/refractory CLL received tirabrutinib 600 mg once daily.
Tirabrutinib 300 mg Twice Daily (CLL)	Tirabrutinib	Participants with relapsed/refractory CLL received tirabrutinib 300 mg twice daily.
Tirabrutinib 160 mg Once Daily (NHL)	Tirabrutinib	Participants with relapsed/refractory NHL received tirabrutinib 160 mg once daily.
Tirabrutinib 80 mg Once Daily (NHL)	Tirabrutinib	Participants with relapsed/refractory NHL received tirabrutinib 80 mg once daily.
Tirabrutinib 320 mg Once Daily (NHL)	Tirabrutinib	Participants with relapsed/refractory NHL received tirabrutinib 320 mg once daily.
Tirabrutinib 600 mg Once Daily (NHL)	Tirabrutinib	Participants with relapsed/refractory NHL received tirabrutinib 600 mg once daily.
Tirabrutinib 20 mg Once Daily (NHL)	Tirabrutinib	Participants with relapsed/refractory non-Hodgkin's lymphoma (NHL) received tirabrutinib 20 mg once daily.
Tirabrutinib 320 mg Once Daily (CLL)	Tirabrutinib	Participants with relapsed/refractory CLL received tirabrutinib 320 mg once daily.
Tirabrutinib 40 mg Once Daily (CLL)	Tirabrutinib	Participants with relapsed/refractory CLL received tirabrutinib 40 mg once daily.
Tirabrutinib 80 mg Once Daily (CLL)	Tirabrutinib	Participants with relapsed/refractory CLL received tirabrutinib 80 mg once daily.
Tirabrutinib 480 mg Once Daily (NHL)	Tirabrutinib	Participants with relapsed/refractory NHL received tirabrutinib 480 mg once daily.
Tirabrutinib 240 mg Twice Daily (NHL)	Tirabrutinib	Participants with relapsed/refractory NHL received tirabrutinib 240 mg twice daily.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Experiencing Dose-Limiting Toxicities	Day 1 through Day 28	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.

Secondary Outcome Measures

Name	Time	Method
PK Parameter: AUCtau of Tirabrutinib	Pre-dose, then 30 minutes, 1, 2, 3, 4, 6, 8, 12 hours post-dose at Cycle 1, Day 28	AUCtau is defined as concentration of drug over dosing interval.
Overall Response Rate	Up to Cycle 37 (28 days for each cycle) plus 6-month intervals thereafter until disease progression (maximum: up to 39 months)	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
Pharmacokinetic (PK) Parameter: Cmax of Tirabrutinib	Pre-dose, then 30 minutes, 1, 2, 3, 4, 6, 8, 12 hours post-dose at Cycle 1, Day 28	Cmax is defined as the maximum concentration of drug.

Trial Locations

Locations (6)

CHU St Eloi; 🇫🇷 Montpellier, France

CHRU - Hopital Claude HURIEZ; 🇫🇷 Lille, France

Centre hospitalier Lyon Sud; 🇫🇷 Lyon, France

University Hospital of Wales; 🇬🇧 Cardiff, United Kingdom

Leicester Royal Infirmary; 🇬🇧 Leicester, United Kingdom

Derriford Hospital; 🇬🇧 Plymouth, United Kingdom