NCT01659255

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).

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
90

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Aug 2012

Typical duration for phase_1

Geographic Reach
2 countries

6 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 6, 2012

Completed
1 month until next milestone

First Posted

Study publicly available on registry

August 7, 2012

Completed
10 days until next milestone

Study Start

First participant enrolled

August 17, 2012

Completed
2.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 23, 2015

Completed
11 months until next milestone

Study Completion

Last participant's last visit for all outcomes

January 11, 2016

Completed
5.1 years until next milestone

Results Posted

Study results publicly available

January 28, 2021

Completed
Last Updated

March 16, 2021

Status Verified

February 1, 2021

Enrollment Period

2.5 years

First QC Date

July 6, 2012

Results QC Date

January 6, 2021

Last Update Submit

February 22, 2021

Conditions

Non Hodgkins LymphomaChronic Lymphocytic Leukaemia

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (3)

  • 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)

  • 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

  • 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

Study Arms (17)

Tirabrutinib 20 mg Once Daily (CLL)

EXPERIMENTAL

Participants with relapsed/refractory chronic lymphocytic leukaemia (CLL) received tirabrutinib 20 mg once daily.

Drug: Tirabrutinib

Tirabrutinib 40 mg Once Daily (CLL)

EXPERIMENTAL

Participants with relapsed/refractory CLL received tirabrutinib 40 mg once daily.

Drug: Tirabrutinib

Tirabrutinib 80 mg Once Daily (CLL)

EXPERIMENTAL

Participants with relapsed/refractory CLL received tirabrutinib 80 mg once daily.

Drug: Tirabrutinib

Tirabrutinib 160 mg Once Daily (CLL)

EXPERIMENTAL

Participants with relapsed/refractory CLL received tirabrutinib 160 mg once daily.

Drug: Tirabrutinib

Tirabrutinib 320 mg Once Daily (CLL)

EXPERIMENTAL

Participants with relapsed/refractory CLL received tirabrutinib 320 mg once daily.

Drug: Tirabrutinib

Tirabrutinib 400 mg Once Daily (CLL)

EXPERIMENTAL

Participants with relapsed/refractory CLL received tirabrutinib 400 mg once daily.

Drug: Tirabrutinib

Tirabrutinib 500 mg Once Daily (CLL)

EXPERIMENTAL

Participants with relapsed/refractory CLL received tirabrutinib 500 mg once daily.

Drug: Tirabrutinib

Tirabrutinib 600 mg Once Daily (CLL)

EXPERIMENTAL

Participants with relapsed/refractory CLL received tirabrutinib 600 mg once daily.

Drug: Tirabrutinib

Tirabrutinib 300 mg Twice Daily (CLL)

EXPERIMENTAL

Participants with relapsed/refractory CLL received tirabrutinib 300 mg twice daily.

Drug: Tirabrutinib

Tirabrutinib 20 mg Once Daily (NHL)

EXPERIMENTAL

Participants with relapsed/refractory non-Hodgkin's lymphoma (NHL) received tirabrutinib 20 mg once daily.

Drug: Tirabrutinib

Tirabrutinib 40 mg Once Daily (NHL)

EXPERIMENTAL

Participants with relapsed/refractory NHL received tirabrutinib 40 mg once daily.

Drug: Tirabrutinib

Tirabrutinib 80 mg Once Daily (NHL)

EXPERIMENTAL

Participants with relapsed/refractory NHL received tirabrutinib 80 mg once daily.

Drug: Tirabrutinib

Tirabrutinib 160 mg Once Daily (NHL)

EXPERIMENTAL

Participants with relapsed/refractory NHL received tirabrutinib 160 mg once daily.

Drug: Tirabrutinib

Tirabrutinib 320 mg Once Daily (NHL)

EXPERIMENTAL

Participants with relapsed/refractory NHL received tirabrutinib 320 mg once daily.

Drug: Tirabrutinib

Tirabrutinib 480 mg Once Daily (NHL)

EXPERIMENTAL

Participants with relapsed/refractory NHL received tirabrutinib 480 mg once daily.

Drug: Tirabrutinib

Tirabrutinib 600 mg Once Daily (NHL)

EXPERIMENTAL

Participants with relapsed/refractory NHL received tirabrutinib 600 mg once daily.

Drug: Tirabrutinib

Tirabrutinib 240 mg Twice Daily (NHL)

EXPERIMENTAL

Participants with relapsed/refractory NHL received tirabrutinib 240 mg twice daily.

Drug: Tirabrutinib

Interventions

TirabrutinibDRUG

Capsules administered orally

Also known as: ONO/GS-4059
Tirabrutinib 160 mg Once Daily (CLL)Tirabrutinib 160 mg Once Daily (NHL)Tirabrutinib 20 mg Once Daily (CLL)Tirabrutinib 20 mg Once Daily (NHL)Tirabrutinib 240 mg Twice Daily (NHL)Tirabrutinib 300 mg Twice Daily (CLL)Tirabrutinib 320 mg Once Daily (CLL)Tirabrutinib 320 mg Once Daily (NHL)Tirabrutinib 40 mg Once Daily (CLL)Tirabrutinib 40 mg Once Daily (NHL)Tirabrutinib 400 mg Once Daily (CLL)Tirabrutinib 480 mg Once Daily (NHL)Tirabrutinib 500 mg Once Daily (CLL)Tirabrutinib 600 mg Once Daily (CLL)Tirabrutinib 600 mg Once Daily (NHL)Tirabrutinib 80 mg Once Daily (CLL)Tirabrutinib 80 mg Once Daily (NHL)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (6)

CHRU - Hopital Claude HURIEZ

Lille, 59037, France

Location

Centre hospitalier Lyon Sud

Lyon, 69495, France

Location

CHU St Eloi

Montpellier, 34295, France

Location

University Hospital of Wales

Cardiff, CF14 4XW, United Kingdom

Location

Leicester Royal Infirmary

Leicester, LE1 5WW, United Kingdom

Location

Derriford Hospital

Plymouth, PL6 8DH, United Kingdom

Location

Related Publications (4)

  • 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.

    PMID: 27248633RESULT

  • 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.

    PMID: 26542378RESULT

  • 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.

    RESULT

  • 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.

    RESULT

MeSH Terms

Conditions

Lymphoma, Non-HodgkinLeukemia, B-Cell

Interventions

tirabrutinib

Condition Hierarchy (Ancestors)

LymphomaNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesLeukemia, LymphoidLeukemiaHematologic Diseases

Results Point of Contact

Title
Gilead Clinical Study Information Center
Organization
Gilead Sciences
GileadClinicalTrials@gilead.com
1-833-445-3230 (GILEAD-0)

Study Officials

  • Gilead Study Director

    Gilead Sciences

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 6, 2012

First Posted

August 7, 2012

Study Start

August 17, 2012

Primary Completion

February 23, 2015

Study Completion

January 11, 2016

Last Updated

March 16, 2021

Results First Posted

January 28, 2021

Record last verified: 2021-02

Locations

FR(3)GB(3)