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)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Janssen - Cilag International

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

19 Apr 2018 → ongoing

Decision date (initial)

2023-10-23

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2023-503469-49-00

EudraCT number

2017-004699-77

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety, Pharmacokinetic

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)

Conditions and MedDRA coding

Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL)

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

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 <70 mL/min using Cockcroft-Gault equation
2. Diagnosis of CLL or SLL that meets iwCLL criteria
3. Active CLL/SLL requiring treatment per the iwCLL criteria: a. Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia or thrombocytopenia or both; b. Massive (ie, at least 6 cm below the left costal margin) or progressive or symptomatic splenomegaly; c. Massive nodes (ie, at least 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy; d. Progressive lymphocytosis with an increase of more than 50% over a 2-month period or lymphocyte doubling time of less than six months; e. Constitutional symptoms, defined as 1 or more of the following: - Unintentional weight loss ≥10% within the previous 6 months prior to the start of screening; - Significant fatigue (inability to work or perform usual activities); - Fevers higher than 100.5°F or 38.0°C for 2 or more weeks without evidence of infection; - Night sweats for more than 1 month without evidence of infection
4. Measurable nodal disease (by computed tomography [CT]), defined as at least one lymph node >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)

Exclusion criteria 14

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
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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression-free survival (PFS) as assessed by an Independent Review Committee (IRC)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Janssen - Cilag International

Sponsor organisation

Janssen - Cilag International

Address

Turnhoutseweg 30

City

Beerse

Postcode

2340

Country

Belgium

Scientific contact point

Organisation

Janssen - Cilag International

Contact name

CTIS Point of Contact

Public contact point

Organisation

Janssen - Cilag International

Contact name

CTIS Point of Contact

Third parties 7

Locations

8 EU/EEA countries · 25 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 117 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications