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STATUS Recruitment Complete

Dose Escalation and Dose Expansion Study of Tirabrutinib in Combination With Other Targeted Anti-cancer Therapies in Adults With B-cell Malignancies

LAST UPDATED

December 13, 2023

Clinicaltrials.gov ID

NCT02457598

EudraCT ID

2015-000834-30

OVERVIEW

A Phase 1b Dose Escalation and Dose Expansion Study of Tirabrutinib (ONO/GS-4059) in Combination With Other Targeted Anti-cancer Therapies in Subjects With B-cell Malignancies

PROTOCOL SUMMARY

The primary objectives of this study are to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy of tirabrutinib (ONO/GS-4059) in combination with other targeted anti-cancer therapies and to evaluate the long-term safety of tirabrutinib as a monotherapy and in combination with other targeted anti-cancer therapies in adults with relapsed or refractory B-cell lymphoproliferative malignancies. This study consists of three parts: Dose Escalation, Dose Expansion, and Long-term Safety Monitoring. During the Dose Escalation phase, participants will be sequentially enrolled in a standard 3 + 3 dose escalation study design, to receive oral tirabrutinib combined with idelalisib entospletinib +/- obinutuzumab. The Dose Expansion Phase will enroll additional participants with a single B-cell lymphoproliferative malignancy disease type to further evaluate efficacy, safety, tolerability, PK, and pharmacodynamics. The Long-term Safety Monitoring phase will evaluate the long-term safety of tirabrutinib both as a monotherapy and in combination with other anti-cancer therapies. As of Amendment 9, all participants currently on the study who have no clinical evidence of disease progression will transition into long-term safety monitoring. Participants from the ongoing Study GS-US-401-1787 and participants who came off Study GS-US-401-1757 and Study GS-US-401-1787 but continued to receive treatment via named patient use (or individual expanded use) will be enrolled into the long-term safety monitoring group (Group VI). Participants enrolled in Group VI will continue the same treatment regimen in Study GS-US-401-1787 or named patient use (or individual expanded use). As of Protocol Amendment 8, the maximum treatment duration for any participant is an additional 6 years from the date of this amendment (ie. until November 2025). As of Amendment 9, entospletinib will be provided until 31 December 2020 to participants who are currently receiving entospletinib. Participants treated with entospletinib as part of a combination regimen with tirabrutinib will stop receiving entospletinib by 31 December 2020 but may continue to be treated with tirabrutinib monotherapy. Idelalisib will be provided as 50 mg tablets until 31 December 2020 and 100 mg tablets until study completion. Participants assigned to the 50 mg tablet will be given the option, at the investigator's discretion, to switch to 100 mg once daily idelalisib dose.

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Participation Requirements

Calendar

Age

18 Years +

Condition

Sex

All

Healthy Icon

Healthy Volunteers

No

Study Details

Medical Condition

B-cell Malignancies

Gender

N/A

Date

June 2015 - December 2025

Study Type

Interventional

Study Phase

Phase 1

Product

Tirabrutinib, Idelalisib, Entospletinib, Obinutuzumab

Eligibility Information

Inclusion

Inclusion Criteria

  • Diagnosis of follicular lymphoma (FL), marginal zone lymphoma (MZL), small lymphocytic lymphoma (SLL), chronic lymphocytic leukemia (CLL) (meeting International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Criteria 2008), mantle cell lymphoma (MCL), Waldenstrom's macroglobulinemia (WM), or non-germinal center B-cell lymphoma (GCB) diffuse large B-cell lymphoma (DLBCL) as documented by medical records on World Health Organization (WHO) criteria
  • Prior treatment for FL, MZL, SLL, MCL, WM with ≥ 2 or for CLL or non-GCB DLBCL ≥ 1 chemotherapy-based or immunotherapy-based regimen, and not transplant eligible and have had either progressive disease (PD) or no response to previous treatment
  • For diseases other than Waldenstrom's macroglobulinemia (WM), presence of radiographically measurable presence of ≥ 1 lesion that measures ≥ 2.0 cm in the longest dimension (LD) and ≥ 1.0 cm in the longest perpendicular dimension (LPD)
  • Eastern Cooperative Oncology Group (ECOG) ≤ 2
  • Platelets ≥ 50 x 10^9/L; Hb ≥ 8.0 g/dL; absolute neutrophil count (ANC) ≥ 1.0 x 10^9/L
  • Without transfusion and growth factors within 7 days
  • Aspartate transaminase/alanine transaminase (AST/ALT) ≤ 2.5 x upper limit of normal (ULN)
  • Total bilirubin ≤ 1.5 x ULN
  • Creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 60 mL/min
  • Not pregnant
  • Willingness and ability to comply with protocol-specified Pneumocystis jirovecii pneumonia (PJP) prophylaxis
  • Long-term Safety Monitoring group only (Group VI):
  • Currently enrolled in Study GS-US-401-1787 or previously enrolled in Study GS-US-401-1757 or Study GS-US-401-1787 and currently receiving continued treatment via named patient use
  • Continuing to benefit from the current treatment regimen in the opinion of the investigator/treating physician
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Exclusion

Exclusion Criteria

  • Hepatitis B surface antigen (HBsAG) positive or hepatitis B core antibody positive
  • Hepatitis C virus (HCV) antibody positive
  • History of long QT syndrome or whose corrected QT(QTc) interval measured (Fridericia method) at screening is prolonged (>450 ms)
  • Long-term Safety Monitoring group only (Group VI):
  • Evidence of clinical or radiological disease progression
  • Note: Other protocol defined Inclusion/Exclusion criteria may apply.
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Locations

Locations (15)
Other

Georgetown University Medical Center

Washington, District of Columbia, United States, 20007

Other

Indiana University Health Goshen Center for Cancer Care

Goshen, Indiana, United States, 46506

Other

Oregon Health and Science University

Portland, Oregon, United States, 97239

Other

CHRU de Lille, Hopital Claude Huriez

Lille, France, 59037

Other

Hopital Saint Eloi

Montpellier, France, 34295

Other

Chu Haut Leveque

Pessac, France, 33604

Other

Centre Hospitalier de Lyon Sud

Pierre Benite, France, 69310

Other

Institut Universitaire du Cancer-Oncopole I.U.C.T-O

Toulouse, France, 3110

Other

Cambridge University Hospitals NHS Foundation Trust

Cambridge, United Kingdom, CB20QQ

Other

Cardiff and Vale Health Board, Clinical Research Facility

Cardiff, United Kingdom, CF14 4XW

Other

Leeds Teaching Hosptials NHS Trust, Dept of Haematology

Leeds, United Kingdom, LS9 7TF

Other

University Hospitals of Leicester NHS Trust

Leicester, United Kingdom, LE1 5WW

Other

The Christie NHS Foundation Trust

Manchester, United Kingdom, M20 4BX

Other

Plymouth Hospitals NHS Trust

Plymouth, United Kingdom, PL68DH

Other

University Hospital Southampton NHS Foundation Trust

Southampton, United Kingdom, SO16 6YD