Chronic Lymphocytic Leukemia Clinical Trial

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

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.

View Eligibility Criteria

Eligibility Criteria

Key Inclusion Criteria:

Diagnosis of follicular lymphoma (FL), marginal zone lymphoma (MZL), small lymphocytic lymphoma (SLL), leukemia-cll/" >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

Key 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.

Study is for people with:

Chronic Lymphocytic Leukemia

Phase:

Phase 1

Estimated Enrollment:

202

Study ID:

NCT02457598

Recruitment Status:

Active, not recruiting

Sponsor:

Gilead Sciences

Check Your Eligibility

Let’s see if you might be eligible for this study.

What is your age and gender ?

Submit

There are 15 Locations for this study

See Locations Near You

Georgetown University Medical Center
Washington District of Columbia, 20007, United States
Indiana University Health Goshen Center for Cancer Care
Goshen Indiana, 46506, United States
Oregon Health and Science University
Portland Oregon, 97239, United States
CHRU de Lille, Hopital Claude Huriez
Lille , 59037, France
Hopital Saint Eloi
Montpellier , 34295, France
Chu Haut Leveque
Pessac , 33604, France
Centre Hospitalier de Lyon Sud
Pierre Benite , 69310, France
Institut Universitaire du Cancer-Oncopole I.U.C.T-O
Toulouse , 3110, France
Cambridge University Hospitals NHS Foundation Trust
Cambridge , CB20Q, United Kingdom
Cardiff and Vale Health Board, Clinical Research Facility
Cardiff , CF14 , United Kingdom
Leeds Teaching Hosptials NHS Trust, Dept of Haematology
Leeds , LS9 7, United Kingdom
University Hospitals of Leicester NHS Trust
Leicester , LE1 5, United Kingdom
The Christie NHS Foundation Trust
Manchester , M20 4, United Kingdom
Plymouth Hospitals NHS Trust
Plymouth , PL68D, United Kingdom
University Hospital Southampton NHS Foundation Trust
Southampton , SO16 , United Kingdom

How clear is this clinincal trial information?

Study is for people with:

Chronic Lymphocytic Leukemia

Phase:

Phase 1

Estimated Enrollment:

202

Study ID:

NCT02457598

Recruitment Status:

Active, not recruiting

Sponsor:


Gilead Sciences

How clear is this clinincal trial information?

×

Introducing, the Journey Bar

Use this bar to access information about the steps in your cancer journey.