A Phase 3 Study of BGB-3111 Compared with Bendamustine plus Rituximab in Patients with Previously Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
- Conditions
- ntreated Chronic Lymphocytic Leukemia or Small Lymphocytic LymphomaMedDRA version: 21.0Level: LLTClassification code 10003946Term: B-Lymphocytic, CLL (Kiel Classification)System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.1Level: LLTClassification code 10041152Term: Small lymphocytic lymphoma, consistent with CLL (Working Formulation)System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-001551-31-PL
- Lead Sponsor
- BeiGene, Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 740
1.Patients must be unsuitable for treatment with FCR defined as: = 65 years of age at the time of informed consent, OR 18 - 64 years of age and have one or more of the following factors:
a.Cumulative Illness Rating Scale (CIRS) score > 6. A CIRS is not required, it may be used to meet this inclusion requirement.
b.Creatinine clearance < 70 mL/min
c.History of previous serious infection or multiple infections in the past 2 years
NOTE: For Arm D only:
-Patients without del17p: must meet one of the above criteria for unsuitability for FCR.
-Patients with del17p/TP53 variant:central laboratory confirmation of del17p-positive CLL/SLL will fulfill the requirement for unsuitability for FCR.For patients with a central FISH test result other than del17p-positive CLL/SLL, a local laboratory test result documenting pathogenic TP53 variant may meet this requirement (refer to Appendix 18 of PA5).
2. Confirmed diagnosis of CD20-positive CLL or SLL that meets the CLL criteria (Hallek et al, 2008)
3. Measurable disease by CT/MRI. Measurable disease is defined as = 1 lymph node > 1.5 cm in longest diameter and measurable in 2 perpendicular diameters.
4. CLL/SLL requiring treatment
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
6. Life expectancy = 6 months
7. Adequate bone marrow function
8. Patient must have adequate organ function
9. Female patients of childbearing potential must practice highly effective methods of contraception initiated prior to first dose of study drug, for the duration of the study, and for = 90 days after the last dose of zanubrutinib, = 30 days after the last dose of venetoclax, 3 months after the last dose of bendamustine, or 12 months after the last dose of rituximab, whichever is longer.
10. Male patients are eligible if vasectomized or if they agree to the use of barrier contraception with other methods described above during the study treatment period and for = 90 days after the last dose of zanubrutinib or 3 months after the last dose of bendamustine whichever is longer.
11. Ability to provide written informed consent and can understand and comply with the requirements of the study
12.Must have FISH results from the study-specified central laboratory confirming the presence or absence of del17p.For Arm D only: Patients must have a central laboratory FISH test for del17p performed. A patient with a result other than with del17p may be eligible for enrollment into the del17p-positive subset only if the patient has a pathogenic TP53 variant previously documented per local laboratory test meeting the criteria specified in Appendix 18. Approval for enrollment by the medical monitor is required.
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 185
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 555
1. Previous systemic treatment for CLL/SLL
2. Requires ongoing need for corticosteroid treatment. NOTE: Systemic corticosteroids must be fully tapered off/stopped at least 5 days before day of first study drug
3. Known prolymphocytic leukemia or history of, or currently suspected, Richter's transformation
4. Clinically significant cardiovascular disease
5. Prior malignancy within the past 3 years, except for curatively treated basal or squamous cell skin cancer, non-muscle-invasive superficial bladder cancer, or carcinoma in situ of the cervix or breast, or localized Gleason score 6 prostate cancer.
6. History of severe bleeding disorder
7. History of stroke or intracranial hemorrhage within 6 months before first dose of study drug
8. Severe or debilitating pulmonary disease
9. Unable to swallow capsules or disease significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, bariatric surgery procedures, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction
10. Active fungal, bacterial and/or viral infection requiring systemic therapy
11. Known central nervous system involvement by leukemia or lymphoma
12. Underlying medical conditions that, in the investigator's opinion, will render the administration of study drug hazardous or obscure the interpretation of toxicity or AEs
13. Known infection with HIV, or serologic status reflecting active hepatitis B or C infection
14. Major surgery within 4 weeks of the first dose of study drug
15. Pregnant or lactating women
16. Vaccination with a live vaccine within 35 days prior to the first dose of study drug
17. Ongoing alcohol or drug addiction
18. Hypersensitivity to zanubrutinib, bendamustine, or rituximab or venetoclax (as applicable) or any of the other ingredients of the applicable study drugs
19. Requires ongoing treatment with a strong CYP3A inhibitor or inducer
20. Concurrent participation in another therapeutic clinical stdy
21. Active and/or ongoing autoimmune anemia and/or autoimmune thrombocytopenia (eg, idiopathic thrombocytopenia purpura).
22. Arm D only: requires ongoing treatment with warfarin or warfarin derivatives.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method