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Relapsed/Refractory B-cell MalignanciesPhase 1NCT02457559

Study to Assess the Long-term Safety and Efficacy of Tirabrutinib in Adults With Relapsed/Refractory B-cell Malignancies

A Phase 1 study testing Tirabrutinib in people with Relapsed/Refractory B-cell Malignancies, run by Gilead Sciences at 6 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The primary objective of this study is to determine the long-term safety and tolerability of tirabrutinib in adults with relapsed/refractory B-cell malignancy who have tolerated and achieved stable disease or improved with tirabrutinib treatment while enrolled in a prior (parent study) tirabrutinib study… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Relapsed/Refractory B-cell Malignancies
What is being tested?
Tirabrutinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
29 participants
Where
6 sitesin 2 countries
Study dates
10 Sep 2015to 30 Dec 2020
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Currently enrolled in a prior tirabrutinib study
  • Did not discontinue treatment with tirabrutinib for any reason other than to enroll in this study
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 at enrollment in this study
  • Any Grade 3 or 4 non-hematologic toxicity that the investigator considers related to previous tirabrutinib use must have resolved, reverted to Grade 1, or reverted to the baseline of the prior study prior to Day 1 of this study
  • Negative serum and urine pregnancy test is required for female individuals (unless surgically sterile or greater than 2 years post menopausal)
  • Male and female individuals of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception as described in the protocol
Show all 9Show fewer
  • Lactating females must agree to discontinue nursing before the study drug is administered
  • Ability and agreement to attend protocol-specified visits at the study site
  • Able to comprehend and willing to sign the informed consent form

Who cannot join

  • Known hypersensitivity to tirabrutinib, its metabolites, or formulation excipients
  • Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial locations and contacts

6 sites in 2 countries.

6 sites in 2 countries

France3 sites

  • CHRU de Lille

    Lille, Nord, 59037

  • Hopital Saint Eloi

    Montpellier, 34295

  • Centre Hospitalier Lyon Sud

    Pierre-Bénite, 69310

Other trials in France

United Kingdom3 sites

  • University Hospital of Wales

    Cardiff, CF14 4XW

  • Leicester Royal Infirmary

    Leicester, LE1 5WW

  • Derriford Hospital

    Plymouth, PL68DH

Other trials in United Kingdom

About this study

Official title: An Open-label Study to Assess the Long-term Safety and Efficacy of ONO/GS-4059 in Subjects With Relapsed/Refractory B-cell Malignancies

The primary objective of this study is to determine the long-term safety and tolerability of tirabrutinib in adults with relapsed/refractory B-cell malignancy who have tolerated and achieved stable disease or improved with tirabrutinib treatment while enrolled in a prior (parent study) tirabrutinib study (NCT01659255). The dosing regimen will be based on the prior dosing regimen from the parent study.

Being tested
Tirabrutinib
Medical subject headings
Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TirabrutinibDrug

    Also called ONO/GS-4059

    Tablets or capsules administered orally

Study groups in NCT02457559
Study groupRoleWhat they receive
Tirabrutinib 40 mg once daily (CLL)ExperimentalParticipants with relapsed/refractory chronic lymphocytic leukemia (CLL) received tirabrutinib 40 mg once daily for up to 96 months from first dose in the parent study.
Receives: Drug: Tirabrutinib
Tirabrutinib 80 mg once daily (CLL)ExperimentalParticipants with relapsed/refractory CLL received tirabrutinib 80 mg once daily for up to 96 months from first dose in the parent study.
Receives: Drug: Tirabrutinib
Tirabrutinib 160 mg once daily (CLL)ExperimentalParticipants with relapsed/refractory CLL received tirabrutinib 160 mg once daily for up to 96 months from first dose in the parent study.
Receives: Drug: Tirabrutinib
Tirabrutinib 320 mg once daily (CLL)ExperimentalParticipants with relapsed/refractory CLL received tirabrutinib 320 mg once daily for up to 96 months from first dose in the parent study.
Receives: Drug: Tirabrutinib
Tirabrutinib 400 mg once daily (CLL)ExperimentalParticipants with relapsed/refractory CLL received tirabrutinib 400 mg once daily for up to 96 months from first dose in the parent study.
Receives: Drug: Tirabrutinib
Tirabrutinib 500 mg once daily (CLL)ExperimentalParticipants with relapsed/refractory CLL received tirabrutinib 500 mg once daily for up to 96 months from first dose in the parent study.
Receives: Drug: Tirabrutinib
Tirabrutinib 600 mg once daily (CLL)ExperimentalParticipants with relapsed/refractory CLL received tirabrutinib 600 mg once daily for up to 96 months from first dose in the parent study.
Receives: Drug: Tirabrutinib
Tirabrutinib 300 mg twice daily (CLL)ExperimentalParticipants with relapsed/refractory CLL received tirabrutinib 300 mg twice daily for up to 96 months from first dose in the parent study.
Receives: Drug: Tirabrutinib
Tirabrutinib 160 mg once daily (NHL)ExperimentalParticipants with relapsed/refractory non-Hodgkin's lymphoma (NHL) received tirabrutinib 160 mg once daily for up to 96 months from first dose in the parent study.
Receives: Drug: Tirabrutinib
Tirabrutinib 320 mg once daily (NHL)ExperimentalParticipants with relapsed/refractory NHL received tirabrutinib 320 mg once daily for up to 96 months from first dose in the parent study.
Receives: Drug: Tirabrutinib
Tirabrutinib 480 mg once daily (NHL)ExperimentalParticipants with relapsed/refractory NHL received tirabrutinib 480 mg once daily for up to 96 months from first dose in the parent study.
Receives: Drug: Tirabrutinib
Tirabrutinib 600 mg once daily (NHL)ExperimentalParticipants with relapsed/refractory NHL received tirabrutinib 600 mg once daily for up to 96 months from first dose in the parent study.
Receives: Drug: Tirabrutinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (AEs)

    Treatment-emergent AEs were defined as one or both of the following:

    • Any AEs with an onset date on or after the study drug start date of parent study and no later than 30 days after permanent discontinuation of study drug in this rollover study;
    • Any AEs leading to premature discontinuation of study drug.

    Measured: First dose of tirabrutinib up to 36 months in the parent study and up to 61 months in the rollover study

  2. Percentage of Participants Who Experienced Treatment-Emergent Marked Laboratory Abnormalities

    Treatment-emergent marked laboratory abnormalities were defined as values that increase from baseline by at least 3 toxicity grades at any postbaseline time point, up to and including the date of the last dose of study drug plus 30. If the relevant baseline laboratory value is missing, any Grade 3 or 4 values observed within the timeframe specified above will be considered treatment-emergent marked abnormalities. Laboratory assessments included tests for Chemistry, Hematology, Coagulation and Urinalysis.

    Measured: First dose of tirabrutinib up to 36 months in the parent study and up to 61 months in the rollover study

Secondary outcomes (4)

  1. Overall Response Rate (ORR)

    ORR was defined per Modified International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria for CLL and Cheson, 2007 criteria for NHL as percentage of participants who achieve partial response (PR) or complete response (CR) in either parent or roll-over study. CLL:CR: lymphocytes (Ly) <4*10^9/L, no lymphadenopathy,normal spleen and liver size,absence of disease, absolute neutrophil count (ANC) >1.5*10^9/L,platelets ≥100*10^9/L, hemoglobin (Hb) >110 g/L,bone marrow at least normocellular for age; PR: ≥2 of these: ≥50% decrease in Ly, lymphadenopathy,size of liver and spleen, bone marrow infiltrates;and ≥1 of these: ANC >1500/μL, platelets ≥100,000/µL, Hb >11g/dL. NHL:CR: complete resolution of all disease-related radiological abnormalities; PR: ≥50% reduction in sum of products (SPD) of the longest diameters (LD) of all index lesions,no new lesions;no increase in size of liver or spleen;persistence of bone marrow involvement in participant who meets other criteria for CR.

    Measured: Up to 39 months in parent study and up to 60 months in rollover study

  2. Duration of Response (DOR)

    DOR was defined per IWCLL 2008 criteria for CLL and Cheson, 2007 criteria for NHL as the interval from first documentation of CR or PR to the earlier of the first documentation of definitive disease progression as assessed by the investigator, or death from any cause in subjects who achieve a response. CLL:CR: Ly <4*10^9/L, no lymphadenopathy, normal spleen and liver size, absence of disease, ANC >1.5*10^9/L, platelets ≥100*10^9/L, Hb >110 g/L, bone marrow at least normocellular for age; PR: ≥2 of these: ≥50% decrease in Ly, lymphadenopathy, size of liver and spleen, bone marrow infiltrates; and ≥1 of these: ANC >1500/μL, platelets ≥100,000/µL, Hb >11 g/dL. NHL:CR: complete resolution of all disease-related radiological abnormalities; PR: ≥50% reduction in SPD of the LD of all index lesions, no new lesions; no increase in size of liver or spleen; persistence of bone marrow involvement in participant who meets other criteria for CR.

    Measured: From first documentation of CR or PR to the first documentation of disease progression or death from any cause up to 39 months in parent study and up to 60 months in the rollover study

  3. Progression-free Survival (PFS)

    PFS was defined per IWCLL 2008 criteria for CLL and Cheson 2007 criteria for NHL as the interval from date of the first dose of tirabrutinib on the parent study to the earlier of the first documentation of definitive disease progression as assessed by the investigator, or death from any cause.

    Progressive disease (PD) in CLL: Lymphadenopathy, or appearance of any new lesion/organomegaly, > 50% increase in the size of the liver and/or spleen, Decrease in platelet count or hemoglobin attributable to CLL per IWCLL, Transformation to a more aggressive histology (eg, Richter syndrome).

    PD in NHL: Cheson, 2007: Appearance of new lesion or increase by >50% of previously involved sites from nadir, Transformation to a more aggressive NHL histology.

    Measured: From first dose of tirabrutinib in the parent study (NCT01659255) to the first documentation of disease progression or death from any cause up to 99 months

  4. Overall Survival (OS)

    OS is defined as the interval from date of the first dose of tirabrutinib on the parent study until death from any cause.

    Measured: From first dose of tirabrutinib in the parent study (NCT01659255) until death from any cause up to 99 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 May 2015 (estimated)
  2. Study start10 Sep 2015
  3. Primary completion30 Dec 2020
  4. Study completion30 Dec 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
29 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02457559
Sponsor's protocol ID
GS-US-401-1787
Other IDs
2015-001404-58, 2015
Status last verified
Mar 2022
First submitted
27 May 2015
Last updated
24 Mar 2022
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Yu H, Truong H, Mitchell SA, Liclican A, Gosink JJ, Li W, Lin J, Feng JY, Jurgensmeier JM, Billin A, Xu R, Patterson S, Pagratis N. Homogeneous BTK Occupancy Assay for Pharmacodynamic Assessment of Tirabrutinib (GS-4059/ONO-4059) Target Engagement. SLAS Discov. 2018 Oct;23(9):919-929. doi: 10.1177/2472555218786165. Epub 2018 Jul 16.

    PubMed 30011241

  • Rule SA, Cartron G, Fegan C, Morschhauser F, Han L, Mitra S, Salles G, Dyer MJS. Long-term follow-up of patients with mantle cell lymphoma (MCL) treated with the selective Bruton's tyrosine kinase inhibitor tirabrutinib (GS/ONO-4059). Leukemia. 2020 May;34(5):1458-1461. doi: 10.1038/s41375-019-0658-7. Epub 2019 Dec 11. No abstract available.

    PubMed 31827243

  • Walter HS, Jayne S, Rule SA, Cartron G, Morschhauser F, Macip S, Karlin L, Jones C, Herbaux C, Quittet P, Shah N, Hutchinson CV, Fegan C, Yang Y, Mitra S, Salles G, Dyer MJS. Long-term follow-up of patients with CLL treated with the selective Bruton's tyrosine kinase inhibitor ONO/GS-4059. Blood. 2017 May 18;129(20):2808-2810. doi: 10.1182/blood-2017-02-765115. Epub 2017 Apr 4. No abstract available.

    PubMed 28377400

  • 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.

    PubMed 26542378

  • 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.

    PubMed 27248633

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Tirabrutinib in people with Relapsed/Refractory B-cell Malignancies, run by Gilead Sciences at 6 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in France, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Mar 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (AEs) (time frame: First dose of tirabrutinib up to 36 months in the parent study and up to 61 months in the rollover study). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02457559, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Mar 2022.

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