Ibrutinib in Previously Untreated Binet Stage a Chronic Lymphocytic Leukemia with Risk of Disease Progression

NCT02863718 | Completed Phase 3 DMC

• 2 other identifiers: CLL122013-003211-22
• Study Type: interventional
• Target: 515
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, multicenter, randomized, placebo-controlled, double-blind phase III study that compares the efficacy and safety of oral ibrutinib in previously untreated Binet stage A CLL patients without treatment indication according to iwCLL guidelines but risk of early disease progression. For event-free survival (EFS), an improvement from 24 months for untreated intermediate or (very) high risk CLL to 48 months for subjects treated with ibrutinib is considered clinically relevant. Ibrutinib / placebo is administered continuously orally until symptomatic disease progression, unacceptable toxicity, or voluntary treatment withdrawal, whichever occurs first.

Conditions

Chronic Lymphocytic Leukemia

Keywords

CLL

Outcome Measures

Primary Outcomes (1)

• Event-free survival (EFS)

  EFS is defined as the time between the date of completed registration and time point of symptomatic disease progression with treatment indication, initiation of subsequent treatment for CLL or death by any cause, whichever occurs first. These will be counted as event for EFS.

  randomization until progression, initiation of subsequent treatment for CLL or death by any cause, whichever occurs first, assessed for at at least 60 months

Secondary Outcomes (5)

• Treatment-free survival

  time of randomization until the date of initiation of subsequent treatment for CLL or death by any cause assessed for at at least 60 months

• Progression-free survival (PFS)

  the time of randomization until symptomatic disease progression (as defined by the updated iwCLL-guidelines) or death by any cause, whichever occurs first, assessed for at at least 60 months

• Response rates (Overall response rate (ORR); Complete Remission (CR); Partial Remission (PR)

  Overall response rate (ORR) achieved during treatment or within 6 months of end of treatment, complete response (CR) and partial response (PR) rates will be evaluated for at least 60 months or Progression whichever occurs first

• rate of Treatment-related adverse events

  randomization until 28 days after the last dose of study drug

• Overall survival (OS)

  date of randomization to the date of death for at least 60 months

Study Arms (3)

Watch & wait

NO INTERVENTION

Watch \& wait

Placebo 420 mg/d

PLACEBO COMPARATOR

Placebo 420mg/d

Drug: Placebo

Ibrutinib 420mg/d

ACTIVE COMPARATOR

Ibrutinib 420mg/d

Drug: Ibrutinib

Interventions

Ibrutinib DRUG

Bruton's tyrosine kinase Inhibitor Ibrutinib 420mg daily

Also known as: Imbruvica

Ibrutinib 420mg/d

Placebo DRUG

Placebo 420mg daily

Placebo 420 mg/d

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Previously untreated CLL
• Stage Binet A without need for treatment
• Age ≥ 18 years
• Life expectancy ≥ 6 months
• ECOG 0 - 2
• Signed written informed consent
• Patient in the experimental arm is willing to use a highly effective contraceptive method
• Male subjects in the experimental treatment arm (placebo / ibrutinib) must:
• Agree to not donate semen during study drug therapy and for a period after end of study drug therapy.
• For males these restrictions apply for 3 months after the last dose of study medication.
• Agree not to share study medication with another person.
• Be counseled about pregnancy precautions and risks of fetal exposure.
• Willingness to inform the general practitioner

You may not qualify if:

• Any prior CLL specific therapy
• Prior treatment with Ibrutinib or BTK inhibitors
• Chronic use of steroids in excess of prednisone 20mg/day or its equivalent
• Active infections requiring systemic antibiotics
• An life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion could compromise the subject's safety, interfere with the absorption or metabolism of Ibrutinib capsules, or put the study outcomes at undue risk
• Pregnant or lactating females
• Central nervous system (CNS) involvement as documented by spinal fluid cytology or imaging. Subjects who have signs or symptoms suggestive of leukemic meningitis or a history of leukemic meningitis must have a lumbar puncture procedure performed within two weeks prior to randomization
• Known second malignancy that limits survival to less than two years
• Known Human Immunodeficiency Virus (HIV), active Hepatitis B Virus (HBV) and/or active Hepatitis C Virus (HCV) infection.
• Any of the following laboratory abnormalities:
• Serum aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) or alanine transaminase (ALT)/serum glutamate pyruvate transaminase (SGPT) \> 2.5 x upper limit of normal (ULN)
• Serum total bilirubin \> 1.5 ULN (with the exception of Gilbert's Syndrome)
• Creatinine clearance \< 30ml/min
• Requires anticoagulant with warfarin or phenoprocoumon
• Requires anticoagulant with oral direct Xa Inhibitors (rivaroxaban, apixaban, edoxaban)

Sponsors & Collaborators

• German CLL Study Group: lead
• Janssen-Cilag Ltd.: collaborator

Study Sites (1)

German CLL Study Group

Cologne, 50935, Germany

Location

Related Publications (2)

• Langerbeins P, Robrecht S, Nieper P, Cramer P, Furstenau M, Al-Sawaf O, Simon F, Fink AM, Kreuzer KA, Vehling-Kaiser U, Tausch E, Schneider C, Muller L, Eckart MJ, Schlag R, Freier W, Gaska T, Balser C, Reiser M, Stauch M, Zahn MO, Dorfel S, Staib P, Behlendorf T, Hensel M, Hebart H, Klaproth H, Block A, Liersch R, Hauch U, Heinrich B, Wendtner CM, Fischer K, Stilgenbauer S, Eichhorst B, Hallek M. Ibrutinib in Early-Stage Chronic Lymphocytic Leukemia: The Randomized, Placebo-Controlled, Double-Blind, Phase III CLL12 Trial. J Clin Oncol. 2025 Feb;43(4):392-402. doi: 10.1200/JCO.24.00975. Epub 2024 Nov 27.

  PMID: 39602678 BACKGROUND

• Langerbeins P, Zhang C, Robrecht S, Cramer P, Furstenau M, Al-Sawaf O, von Tresckow J, Fink AM, Kreuzer KA, Vehling-Kaiser U, Tausch E, Muller L, Eckart MJ, Schlag R, Freier W, Gaska T, Balser C, Reiser M, Stauch M, Wendtner CM, Fischer K, Stilgenbauer S, Eichhorst B, Hallek M. The CLL12 trial: ibrutinib vs placebo in treatment-naive, early-stage chronic lymphocytic leukemia. Blood. 2022 Jan 13;139(2):177-187. doi: 10.1182/blood.2021010845.

  PMID: 34758069 BACKGROUND

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

ibrutinib

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Petra Langerbeins, MD

  German CLL Study Group

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 10, 2014
• First Posted: August 11, 2016
• Study Start: April 30, 2014
• Primary Completion: March 7, 2019
• Study Completion: July 11, 2022
• Last Updated: December 30, 2024

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)