A study of the Combination of Ibrutinib plus Venetoclax versus Chlorambucil plus Obinutuzumab for the First-line Treatment of Patients with Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)

A Randomized, Open-label, Phase 3 study of the Combination of Ibrutinib plus Venetoclax versus Chlorambucil plus Obinutuzumab for the First-line Treatment of Subjects with Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)

Status

Not yet recruiting

Phases

Phase 3

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2017-004699-77-GB

Enrollment

200

Registered

2018-02-01

Start date

2018-06-04

Completion date

Unknown

Last updated

2020-02-01

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL) MedDRA version: 21.0 Level: LLT Classification code 10008976 Term: Chronic lymphocytic leukemia System Organ Class: 100000004864

Interventions

Product Name: Ibrutinib Product Code: JNJ-54179060-AAA Pharmaceutical Form: Capsule, hard INN or Proposed INN: Ibrutinib CAS Number: 936

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1. Adult subjects who are: a. =65 years old or, b. 18 to 64 years old and have at least 1 of the following: - Cumulative Illness Rating Scale (CIRS) score >6 - Creatinine clearance (CrCl) estimated 1.5 cm in longest diameter. 5. ECOG Performance Status Grade =2. 6. Adequate organ function defined as follows: a. Absolute neutrophil count (ANC) =750 cells/µL independent of growth factor support; b. Platelets =50,000 cells/µL independent of transfusion support for at least 7 days prior to randomization; c. Hemoglobin >8.0 g/dL independent of transfusion support for at least 7 days prior to randomization; d. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =3.0 x upper limit of normal (ULN); e. Total bilirubin =1.5 x ULN (unless due to Gilbert’s syndrome); f. Estimated CrCl =30 mL/min (Cockcroft-Gault equation). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 180 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20

Exclusion criteria

Exclusion criteria: 1. Prior anti-leukemic therapy for CLL or SLL. 2. Presence of del17p or known TP53 mutation detected at a threshold of >10% variable allele frequency (VAF). 3. Major surgery within 4 weeks of first dose of study treatment. 4. Known bleeding disorders (eg, von Willebrand’s disease or hemophilia). 5. Central nervous system (CNS) involvement or suspected Richter’s syndrome. 6. An individual organ/system impairment score of 4 as assessed by CIRS, except for the eyes, ears, nose, throat, and larynx system, limiting the ability to receive treatment in this study. 7. Uncontrolled autoimmune hemolytic anemia or autoimmune thrombocytopenia (Coombs positivity in the absence of hemolysis is not an exclusion). 8. Chronic use of corticosteroids more than 20 mg/day of prednisone or its equivalent within 7 days of initiation of study treatment. 9. History of prior malignancy, except: a. Malignancy treated with curative intent and with no known active disease present for =24 months before randomization; b. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease; c. Adequately treated cervical carcinoma in situ without evidence of disease; d. Malignancy, which is considered cured with minimal risk of recurrence. 10. Received live, attenuated vaccine within 4 weeks of randomization. 11. History of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, or hepatic condition that in the opinion of the investigator would adversely affect a subject’s participation in the study. 12. Currently active, clinically significant Child-Pugh Class B or C hepatic impairment according to the Child Pugh classification (see Attachment 4 Child-Pugh classification) 13. Uncontrolled active systemic infection or any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator’s opinion, could compromise the subject’s safety or put the study outcomes at undue risk. 14. Inability or difficulty swallowing capsules/tablets, malabsorption syndrome, or any disease or medical condition significantly affecting gastrointestinal function.

Design outcomes

Primary

Measure	Time frame
Main Objective: To assess progression-free survival (PFS) from treatment with ibrutinib plus venetoclax (I+VEN) compared with obinutuzumab plus chlorambucil (G-Clb) as assessed by an Independent Review Committee (IRC).; Secondary Objective: Key secondary objectives are to evaluate the following: - rate of minimal residual disease (MRD)-negative remissions - overall response rate (ORR), including complete response (CR) rate, and response duration as assessed by an IRC - overall survival (OS) - time to next treatment - trough levels of ibrutinib and venetoclax when given in combination - safety ;Primary end point(s): Progression-free survival (PFS) as assessed by an Independent Review Committee (IRC).;Timepoint(s) of evaluation of this end point: From the date of randomization to date of disease progression or death, whichever occurs first.	—

Measure

Time frame

Main Objective: To assess progression-free survival (PFS) from treatment with ibrutinib plus venetoclax (I+VEN) compared with obinutuzumab plus chlorambucil (G-Clb) as assessed by an Independent Review Committee (IRC).; Secondary Objective: Key secondary objectives are to evaluate the following: - rate of minimal residual disease (MRD)-negative remissions - overall response rate (ORR), including complete response (CR) rate, and response duration as assessed by an IRC - overall survival (OS) - time to next treatment - trough levels of ibrutinib and venetoclax when given in combination - safety ;Primary end point(s): Progression-free survival (PFS) as assessed by an Independent Review Committee (IRC).;Timepoint(s) of evaluation of this end point: From the date of randomization to date of disease progression or death, whichever occurs first.

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Secondary

Measure	Time frame
Secondary end point(s): 1 - Proportion of subjects who reach MRD negative disease status (ie, <1 CLL cell per 10,000 leukocytes or <0.01%) in the bone marrow. 2 - Overall response rate, defined as the proportion of subjects who achieve a response ie, CR, CRi, nPR, and PR. 3 - CR rate, defined as the proportion of subjects who achieve CR. 4 - Response duration in days from the date of initial documentation of a response to the date of first documented evidence of PD or death. 5 - Overall survival. 6 - Time to next treatment. 7 - Time to worsening in functional status and fatigue. 8 - Safety. 9 - Hematologic improvement (hemoglobin and platelets). 10 - Descriptive statistics of ibrutinib and venetoclax trough levels in plasma. ; Timepoint(s) of evaluation of this end point: 1 - Evaluated at week 36 and week 84 2 & 3 - Evaluations will be performed every 12 weeks after randomization through Week 60, then every 16 weeks through Week 156, then every 24 weeks thereafter until disease progression or death 4 - From the date of initial documentation of a response to the date of first documented evidence of PD or death 5 - From the date of randomization to the date of death from any cause 6 - From date of randomization to the start date of any anti-leukemic therapy subsequent to the study treatment 7 - Throughout trial 8 - Throughout trial 9 - Improvement lasting for 56 days without transfusions or growth factors 10 - Cycle 2, 3, 5 and 6	—

Measure

Time frame

Secondary end point(s): 1 - Proportion of subjects who reach MRD negative disease status (ie, <1 CLL cell per 10,000 leukocytes or <0.01%) in the bone marrow. 2 - Overall response rate, defined as the proportion of subjects who achieve a response ie, CR, CRi, nPR, and PR. 3 - CR rate, defined as the proportion of subjects who achieve CR. 4 - Response duration in days from the date of initial documentation of a response to the date of first documented evidence of PD or death. 5 - Overall survival. 6 - Time to next treatment. 7 - Time to worsening in functional status and fatigue. 8 - Safety. 9 - Hematologic improvement (hemoglobin and platelets). 10 - Descriptive statistics of ibrutinib and venetoclax trough levels in plasma. ; Timepoint(s) of evaluation of this end point: 1 - Evaluated at week 36 and week 84 2 & 3 - Evaluations will be performed every 12 weeks after randomization through Week 60, then every 16 weeks through Week 156, then every 24 weeks thereafter until disease progression or death 4 - From the date of initial documentation of a response to the date of first documented evidence of PD or death 5 - From the date of randomization to the date of death from any cause 6 - From date of randomization to the start date of any anti-leukemic therapy subsequent to the study treatment 7 - Throughout trial 8 - Throughout trial 9 - Improvement lasting for 56 days without transfusions or growth factors 10 - Cycle 2, 3, 5 and 6

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Countries

Belgium, Canada, Czech Republic, Denmark, France, Israel, Netherlands, Poland, Russian Federation, Spain, Sweden, Turkey, United Kingdom

Contacts

Public ContactClinical Registry Group

Janssen-Cilag International NV

ClinicalTrialsEU@its.jnj.com+31 71 524 21 66

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026