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

Phase 1

Completed

• Conditions: Relapsed/Refractory B-cell Malignancies
• Interventions: Drug: Tirabrutinib

• Registration Number: NCT02457559
• Lead Sponsor: Gilead Sciences

Brief 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 (NCT01659255). The dosing regimen will be based on the prior dosing regimen from the parent study.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-05-27
• Study First Submitted QC: 2015-05-27
• Study First Posted: 2015-05-29
• Study Start: 2015-09-10
• Primary Completion: 2020-12-30
• Study Completion: 2020-12-30
• Results First Submitted: 2021-12-08
• Status Verified: 2022-03
• Results First Submitted QC: 2022-03-23
• Last Update Submitted: 2022-03-23
• Results First Posted: 2022-03-24
• Last Update Posted: 2022-03-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 29

Inclusion Criteria

• 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
• 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

Key

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Exclusion Criteria

• Known hypersensitivity to tirabrutinib, its metabolites, or formulation excipients

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Tirabrutinib 80 mg once daily (CLL)	Tirabrutinib	Participants with relapsed/refractory CLL received tirabrutinib 80 mg once daily for up to 96 months from first dose in the parent study.
Tirabrutinib 320 mg once daily (CLL)	Tirabrutinib	Participants with relapsed/refractory CLL received tirabrutinib 320 mg once daily for up to 96 months from first dose in the parent study.
Tirabrutinib 600 mg once daily (CLL)	Tirabrutinib	Participants with relapsed/refractory CLL received tirabrutinib 600 mg once daily for up to 96 months from first dose in the parent study.
Tirabrutinib 400 mg once daily (CLL)	Tirabrutinib	Participants with relapsed/refractory CLL received tirabrutinib 400 mg once daily for up to 96 months from first dose in the parent study.
Tirabrutinib 500 mg once daily (CLL)	Tirabrutinib	Participants with relapsed/refractory CLL received tirabrutinib 500 mg once daily for up to 96 months from first dose in the parent study.
Tirabrutinib 160 mg once daily (NHL)	Tirabrutinib	Participants 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.
Tirabrutinib 300 mg twice daily (CLL)	Tirabrutinib	Participants with relapsed/refractory CLL received tirabrutinib 300 mg twice daily for up to 96 months from first dose in the parent study.
Tirabrutinib 320 mg once daily (NHL)	Tirabrutinib	Participants with relapsed/refractory NHL received tirabrutinib 320 mg once daily for up to 96 months from first dose in the parent study.
Tirabrutinib 480 mg once daily (NHL)	Tirabrutinib	Participants with relapsed/refractory NHL received tirabrutinib 480 mg once daily for up to 96 months from first dose in the parent study.
Tirabrutinib 160 mg once daily (CLL)	Tirabrutinib	Participants with relapsed/refractory CLL received tirabrutinib 160 mg once daily for up to 96 months from first dose in the parent study.
Tirabrutinib 40 mg once daily (CLL)	Tirabrutinib	Participants 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.
Tirabrutinib 600 mg once daily (NHL)	Tirabrutinib	Participants with relapsed/refractory NHL received tirabrutinib 600 mg once daily for up to 96 months from first dose in the parent study.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (AEs)	First dose of tirabrutinib up to 36 months in the parent study and up to 61 months in the rollover study	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.
Percentage of Participants Who Experienced Treatment-Emergent Marked Laboratory Abnormalities	First dose of tirabrutinib up to 36 months in the parent study and up to 61 months in the rollover study	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.

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	From first dose of tirabrutinib in the parent study (NCT01659255) until death from any cause up to 99 months	OS is defined as the interval from date of the first dose of tirabrutinib on the parent study until death from any cause.
Progression-free Survival (PFS)	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	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.
Overall Response Rate (ORR)	Up to 39 months in parent study and up to 60 months in rollover study	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.
Duration of Response (DOR)	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	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.

Trial Locations

Locations (6)

Hopital Saint Eloi; 🇫🇷 Montpellier, France

Centre Hospitalier Lyon Sud; 🇫🇷 Pierre Benite, France

Leicester Royal Infirmary; 🇬🇧 Leicester, United Kingdom

Derriford Hospital; 🇬🇧 Plymouth, United Kingdom

University Hospital of Wales; 🇬🇧 Cardiff, United Kingdom

CHRU de Lille; 🇫🇷 Lille, Nord, France