Back to resultsStudy to Evaluate the Safety and Tolerability of Tirabrutinib (ONO/GS-4059) Given as Monotherapy in Participants With Relapsed/Refractory NHL and CLL
Primary Purpose
Non Hodgkins Lymphoma, Chronic Lymphocytic Leukaemia
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Tirabrutinib
Sponsored by
About this trial
This is an interventional treatment trial for Non Hodgkins Lymphoma
Eligibility Criteria
Key Inclusion Criteria:
- 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.
- Age ≥ 18 years.
- Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
Key Exclusion Criteria:
- Central nervous system (CNS) lymphoma.
- Women who are pregnant or lactating.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Sites / Locations
- CHRU - Hopital Claude HURIEZ
- Centre hospitalier Lyon Sud
- CHU St Eloi
- University Hospital of Wales
- Leicester Royal Infirmary
- Derriford Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm 9
Arm 10
Arm 11
Arm 12
Arm 13
Arm 14
Arm 15
Arm 16
Arm 17
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
Tirabrutinib 20 mg Once Daily (CLL)
Tirabrutinib 40 mg Once Daily (CLL)
Tirabrutinib 80 mg Once Daily (CLL)
Tirabrutinib 160 mg Once Daily (CLL)
Tirabrutinib 320 mg Once Daily (CLL)
Tirabrutinib 400 mg Once Daily (CLL)
Tirabrutinib 500 mg Once Daily (CLL)
Tirabrutinib 600 mg Once Daily (CLL)
Tirabrutinib 300 mg Twice Daily (CLL)
Tirabrutinib 20 mg Once Daily (NHL)
Tirabrutinib 40 mg Once Daily (NHL)
Tirabrutinib 80 mg Once Daily (NHL)
Tirabrutinib 160 mg Once Daily (NHL)
Tirabrutinib 320 mg Once Daily (NHL)
Tirabrutinib 480 mg Once Daily (NHL)
Tirabrutinib 600 mg Once Daily (NHL)
Tirabrutinib 240 mg Twice Daily (NHL)
Arm Description
Participants with relapsed/refractory chronic lymphocytic leukaemia (CLL) received tirabrutinib 20 mg once daily.
Participants with relapsed/refractory CLL received tirabrutinib 40 mg once daily.
Participants with relapsed/refractory CLL received tirabrutinib 80 mg once daily.
Participants with relapsed/refractory CLL received tirabrutinib 160 mg once daily.
Participants with relapsed/refractory CLL received tirabrutinib 320 mg once daily.
Participants with relapsed/refractory CLL received tirabrutinib 400 mg once daily.
Participants with relapsed/refractory CLL received tirabrutinib 500 mg once daily.
Participants with relapsed/refractory CLL received tirabrutinib 600 mg once daily.
Participants with relapsed/refractory CLL received tirabrutinib 300 mg twice daily.
Participants with relapsed/refractory non-Hodgkin's lymphoma (NHL) received tirabrutinib 20 mg once daily.
Participants with relapsed/refractory NHL received tirabrutinib 40 mg once daily.
Participants with relapsed/refractory NHL received tirabrutinib 80 mg once daily.
Participants with relapsed/refractory NHL received tirabrutinib 160 mg once daily.
Participants with relapsed/refractory NHL received tirabrutinib 320 mg once daily.
Participants with relapsed/refractory NHL received tirabrutinib 480 mg once daily.
Participants with relapsed/refractory NHL received tirabrutinib 600 mg once daily.
Participants with relapsed/refractory NHL received tirabrutinib 240 mg twice daily.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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
Pharmacokinetic (PK) Parameter: Cmax of Tirabrutinib
Cmax is defined as the maximum concentration of drug.
PK Parameter: AUCtau of Tirabrutinib
AUCtau is defined as concentration of drug over dosing interval.
Full Information
NCT ID
NCT01659255
First Posted
July 6, 2012
Last Updated
February 22, 2021
Sponsor
Gilead Sciences
Collaborators
Ono Pharmaceutical Co. Ltd
1. Study Identification
Unique Protocol Identification Number
NCT01659255
Brief Title
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
2. Study Status
Record Verification Date
February 2021
Overall Recruitment Status
Completed
Study Start Date
August 17, 2012 (Actual)
Primary Completion Date
February 23, 2015 (Actual)
Study Completion Date
January 11, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gilead Sciences
Collaborators
Ono Pharmaceutical Co. Ltd
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non Hodgkins Lymphoma, Chronic Lymphocytic Leukaemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
90 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Tirabrutinib 20 mg Once Daily (CLL)
Arm Type
Experimental
Arm Description
Participants with relapsed/refractory chronic lymphocytic leukaemia (CLL) received tirabrutinib 20 mg once daily.
Arm Title
Tirabrutinib 40 mg Once Daily (CLL)
Arm Type
Experimental
Arm Description
Participants with relapsed/refractory CLL received tirabrutinib 40 mg once daily.
Arm Title
Tirabrutinib 80 mg Once Daily (CLL)
Arm Type
Experimental
Arm Description
Participants with relapsed/refractory CLL received tirabrutinib 80 mg once daily.
Arm Title
Tirabrutinib 160 mg Once Daily (CLL)
Arm Type
Experimental
Arm Description
Participants with relapsed/refractory CLL received tirabrutinib 160 mg once daily.
Arm Title
Tirabrutinib 320 mg Once Daily (CLL)
Arm Type
Experimental
Arm Description
Participants with relapsed/refractory CLL received tirabrutinib 320 mg once daily.
Arm Title
Tirabrutinib 400 mg Once Daily (CLL)
Arm Type
Experimental
Arm Description
Participants with relapsed/refractory CLL received tirabrutinib 400 mg once daily.
Arm Title
Tirabrutinib 500 mg Once Daily (CLL)
Arm Type
Experimental
Arm Description
Participants with relapsed/refractory CLL received tirabrutinib 500 mg once daily.
Arm Title
Tirabrutinib 600 mg Once Daily (CLL)
Arm Type
Experimental
Arm Description
Participants with relapsed/refractory CLL received tirabrutinib 600 mg once daily.
Arm Title
Tirabrutinib 300 mg Twice Daily (CLL)
Arm Type
Experimental
Arm Description
Participants with relapsed/refractory CLL received tirabrutinib 300 mg twice daily.
Arm Title
Tirabrutinib 20 mg Once Daily (NHL)
Arm Type
Experimental
Arm Description
Participants with relapsed/refractory non-Hodgkin's lymphoma (NHL) received tirabrutinib 20 mg once daily.
Arm Title
Tirabrutinib 40 mg Once Daily (NHL)
Arm Type
Experimental
Arm Description
Participants with relapsed/refractory NHL received tirabrutinib 40 mg once daily.
Arm Title
Tirabrutinib 80 mg Once Daily (NHL)
Arm Type
Experimental
Arm Description
Participants with relapsed/refractory NHL received tirabrutinib 80 mg once daily.
Arm Title
Tirabrutinib 160 mg Once Daily (NHL)
Arm Type
Experimental
Arm Description
Participants with relapsed/refractory NHL received tirabrutinib 160 mg once daily.
Arm Title
Tirabrutinib 320 mg Once Daily (NHL)
Arm Type
Experimental
Arm Description
Participants with relapsed/refractory NHL received tirabrutinib 320 mg once daily.
Arm Title
Tirabrutinib 480 mg Once Daily (NHL)
Arm Type
Experimental
Arm Description
Participants with relapsed/refractory NHL received tirabrutinib 480 mg once daily.
Arm Title
Tirabrutinib 600 mg Once Daily (NHL)
Arm Type
Experimental
Arm Description
Participants with relapsed/refractory NHL received tirabrutinib 600 mg once daily.
Arm Title
Tirabrutinib 240 mg Twice Daily (NHL)
Arm Type
Experimental
Arm Description
Participants with relapsed/refractory NHL received tirabrutinib 240 mg twice daily.
Intervention Type
Drug
Intervention Name(s)
Tirabrutinib
Other Intervention Name(s)
ONO/GS-4059
Intervention Description
Capsules administered orally
Primary Outcome Measure Information:
Title
Percentage of Participants Experiencing Dose-Limiting Toxicities
Description
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.
Time Frame
Day 1 through Day 28
Secondary Outcome Measure Information:
Title
Overall Response Rate
Description
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
Time Frame
Up to Cycle 37 (28 days for each cycle) plus 6-month intervals thereafter until disease progression (maximum: up to 39 months)
Title
Pharmacokinetic (PK) Parameter: Cmax of Tirabrutinib
Description
Cmax is defined as the maximum concentration of drug.
Time Frame
Pre-dose, then 30 minutes, 1, 2, 3, 4, 6, 8, 12 hours post-dose at Cycle 1, Day 28
Title
PK Parameter: AUCtau of Tirabrutinib
Description
AUCtau is defined as concentration of drug over dosing interval.
Time Frame
Pre-dose, then 30 minutes, 1, 2, 3, 4, 6, 8, 12 hours post-dose at Cycle 1, Day 28
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
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.
Age ≥ 18 years.
Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
Key Exclusion Criteria:
Central nervous system (CNS) lymphoma.
Women who are pregnant or lactating.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gilead Study Director
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
Facility Name
CHRU - Hopital Claude HURIEZ
City
Lille
ZIP/Postal Code
59037
Country
France
Facility Name
Centre hospitalier Lyon Sud
City
Lyon
ZIP/Postal Code
69495
Country
France
Facility Name
CHU St Eloi
City
Montpellier
ZIP/Postal Code
34295
Country
France
Facility Name
University Hospital of Wales
City
Cardiff
ZIP/Postal Code
CF14 4XW
Country
United Kingdom
Facility Name
Leicester Royal Infirmary
City
Leicester
ZIP/Postal Code
LE1 5WW
Country
United Kingdom
Facility Name
Derriford Hospital
City
Plymouth
ZIP/Postal Code
PL6 8DH
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
27248633
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.
Results Reference
result
PubMed Identifier
26542378
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.
Results Reference
result
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.
Results Reference
result
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.
Results Reference
result
Learn more about this trial
Study to Evaluate the Safety and Tolerability of Tirabrutinib (ONO/GS-4059) Given as Monotherapy in Participants With Relapsed/Refractory NHL and CLL
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