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

February 22, 2021 updated by: Gilead Sciences

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)

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

90

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Lille, France, 59037
        • CHRU - Hôpital Claude Huriez
      • Lyon, France, 69495
        • Centre Hospitalier Lyon Sud
      • Montpellier, France, 34295
        • CHU St Eloi
  • United Kingdom
      • Cardiff, United Kingdom, CF14 4XW
        • University Hospital of Wales
      • Leicester, United Kingdom, LE1 5WW
        • Leicester Royal Infirmary
      • Plymouth, United Kingdom, PL6 8DH
        • Derriford Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Tirabrutinib 20 mg Once Daily (CLL)
Participants with relapsed/refractory chronic lymphocytic leukaemia (CLL) received tirabrutinib 20 mg once daily.
Drug: Tirabrutinib
Capsules administered orally
Other Names:
  • ONO/GS-4059
Experimental: Tirabrutinib 40 mg Once Daily (CLL)
Participants with relapsed/refractory CLL received tirabrutinib 40 mg once daily.
Drug: Tirabrutinib
Capsules administered orally
Other Names:
  • ONO/GS-4059
Experimental: Tirabrutinib 80 mg Once Daily (CLL)
Participants with relapsed/refractory CLL received tirabrutinib 80 mg once daily.
Drug: Tirabrutinib
Capsules administered orally
Other Names:
  • ONO/GS-4059
Experimental: Tirabrutinib 160 mg Once Daily (CLL)
Participants with relapsed/refractory CLL received tirabrutinib 160 mg once daily.
Drug: Tirabrutinib
Capsules administered orally
Other Names:
  • ONO/GS-4059
Experimental: Tirabrutinib 320 mg Once Daily (CLL)
Participants with relapsed/refractory CLL received tirabrutinib 320 mg once daily.
Drug: Tirabrutinib
Capsules administered orally
Other Names:
  • ONO/GS-4059
Experimental: Tirabrutinib 400 mg Once Daily (CLL)
Participants with relapsed/refractory CLL received tirabrutinib 400 mg once daily.
Drug: Tirabrutinib
Capsules administered orally
Other Names:
  • ONO/GS-4059
Experimental: Tirabrutinib 500 mg Once Daily (CLL)
Participants with relapsed/refractory CLL received tirabrutinib 500 mg once daily.
Drug: Tirabrutinib
Capsules administered orally
Other Names:
  • ONO/GS-4059
Experimental: Tirabrutinib 600 mg Once Daily (CLL)
Participants with relapsed/refractory CLL received tirabrutinib 600 mg once daily.
Drug: Tirabrutinib
Capsules administered orally
Other Names:
  • ONO/GS-4059
Experimental: Tirabrutinib 300 mg Twice Daily (CLL)
Participants with relapsed/refractory CLL received tirabrutinib 300 mg twice daily.
Drug: Tirabrutinib
Capsules administered orally
Other Names:
  • ONO/GS-4059
Experimental: Tirabrutinib 20 mg Once Daily (NHL)
Participants with relapsed/refractory non-Hodgkin's lymphoma (NHL) received tirabrutinib 20 mg once daily.
Drug: Tirabrutinib
Capsules administered orally
Other Names:
  • ONO/GS-4059
Experimental: Tirabrutinib 40 mg Once Daily (NHL)
Participants with relapsed/refractory NHL received tirabrutinib 40 mg once daily.
Drug: Tirabrutinib
Capsules administered orally
Other Names:
  • ONO/GS-4059
Experimental: Tirabrutinib 80 mg Once Daily (NHL)
Participants with relapsed/refractory NHL received tirabrutinib 80 mg once daily.
Drug: Tirabrutinib
Capsules administered orally
Other Names:
  • ONO/GS-4059
Experimental: Tirabrutinib 160 mg Once Daily (NHL)
Participants with relapsed/refractory NHL received tirabrutinib 160 mg once daily.
Drug: Tirabrutinib
Capsules administered orally
Other Names:
  • ONO/GS-4059
Experimental: Tirabrutinib 320 mg Once Daily (NHL)
Participants with relapsed/refractory NHL received tirabrutinib 320 mg once daily.
Drug: Tirabrutinib
Capsules administered orally
Other Names:
  • ONO/GS-4059
Experimental: Tirabrutinib 480 mg Once Daily (NHL)
Participants with relapsed/refractory NHL received tirabrutinib 480 mg once daily.
Drug: Tirabrutinib
Capsules administered orally
Other Names:
  • ONO/GS-4059
Experimental: Tirabrutinib 600 mg Once Daily (NHL)
Participants with relapsed/refractory NHL received tirabrutinib 600 mg once daily.
Drug: Tirabrutinib
Capsules administered orally
Other Names:
  • ONO/GS-4059
Experimental: Tirabrutinib 240 mg Twice Daily (NHL)
Participants with relapsed/refractory NHL received tirabrutinib 240 mg twice daily.
Drug: Tirabrutinib
Capsules administered orally
Other Names:
  • ONO/GS-4059

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants Experiencing Dose-Limiting Toxicities
Time Frame: 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.
Day 1 through Day 28

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Response Rate
Time Frame: 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
Up to Cycle 37 (28 days for each cycle) plus 6-month intervals thereafter until disease progression (maximum: up to 39 months)
Pharmacokinetic (PK) Parameter: Cmax of Tirabrutinib
Time Frame: 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.
Pre-dose, then 30 minutes, 1, 2, 3, 4, 6, 8, 12 hours post-dose at Cycle 1, Day 28
PK Parameter: AUCtau of Tirabrutinib
Time Frame: 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.
Pre-dose, then 30 minutes, 1, 2, 3, 4, 6, 8, 12 hours post-dose at Cycle 1, Day 28

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Gilead Sciences

Collaborators

Ono Pharmaceutical Co. Ltd

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 17, 2012

Primary Completion (Actual)

February 23, 2015

Study Completion (Actual)

January 11, 2016

Study Registration Dates

First Submitted

July 6, 2012

First Submitted That Met QC Criteria

August 6, 2012

First Posted (Estimate)

August 7, 2012

Study Record Updates

Last Update Posted (Actual)

March 16, 2021

Last Update Submitted That Met QC Criteria

February 22, 2021

Last Verified

February 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ONO-4059POE001
  • 2011-005033-39 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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