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A Phase 2 Study combining BGB-3111 with Obinutuzumab compared with Obinutuzumab Monotherapy in Relapsed/Refractory Follicular Lymphoma
EU CTIS ID: 2023-509975-17-00
What this study is testing
To evaluate efficacy of zanubrutinib plus obinutuzumab versus obinutuzumab monotherapy, as measured by overall response rate determined by independent central review.
- Therapeutic exploratory (Phase II)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- ≥ 18 years of age at the time of informed consent
- Adequate organ function defined as: a. Absolute neutrophil count (ANC) > 750/mm3 (without growth factor support within 7 days) b. Platelet > 50,000/mm3 (without growth factor support or transfusion within 7 days) c. Creatinine clearance ≥ 30 mL/min (as estimated by the CockcroftGault or MDRD equation or as measured by nuclear medicine scan or 24hour urine collection) d. Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase, and alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase ≤ 3.0 × upper limit of normal (ULN) e. Serum total bilirubin < 2.0 × ULN (unless documented Gilbert's syndrome)
- 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, or 18 months after the last dose of obinutuzumab, whichever is longer. Highly effective contraceptive methods include the following: a. Combined (estrogen and progestogen containing) hormonal contraception associated with the inhibition of ovulation - Oral, intravaginal or transdermal b. Progestogen-only hormonal contraception associated with the inhibition of ovulation - Oral, injectable, implantable c. An intrauterine device d. Intrauterine hormone-releasing system e. Bilateral tubal occlusion f. Vasectomized partner g. Sexual abstinence (defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatment, starting the day prior to first dose of study drug, for the duration of the study, and for ≥ 90 days after the last dose of zanubrutinib, or 18 months after the last dose of obinutuzumab, whichever is longer). Total sexual abstinence should only be used as a contraceptive method if it is in line with the patients' usual and preferred lifestyle. Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of exposure to investigational medicinal product, and withdrawal are not acceptable methods of contraception. Of note, barrier contraception (including male and female condoms with or without spermicide) is not considered a highly effective method of contraception and if used, this method must be used in combination with another acceptable method listed above. For patients using hormonal contraceptives such as birth control pills or devices, a second barrier method of contraception (eg, condoms) must be used.
- Male patients if abstinent (as defined above), are eligible if vasectomized or if they agree to the use of barrier contraception in combination with other methods described above during the study treatment period and for ≥ 90 days after the last dose of zanubrutinib or 18 months after the last dose of obinutuzumab, whichever is longer.
- Ability to provide written informed consent and can understand and comply with the requirements of the study.
- Histologically confirmed diagnosis of B-cell follicular lymphoma (grade 1, 2 or 3a) based on the WHO 2008 classification of tumors of hematopoietic and lymphoid tissue
You likely can't join if
- Known central nervous system involvement by leukemia or lymphoma
- 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
- Active fungal, bacterial and/or viral infection requiring systemic therapy
- Underlying medical conditions that, in the investigator's opinion, will render the administration of study drug hazardous or obscure the interpretation of safety or efficacy results
- Known infection with HIV, or serologic status reflecting active hepatitis B or C infection as follows: a. Presence of hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb). Patients with presence of HBcAb, but absence of HBsAg, are eligible if hepatitis B virus (HBV) DNA is undetectable (< 20 IU/mL), and if they are willing to undergo monthly monitoring for HBV reactivation. b. Presence of hepatitis C virus (HCV) antibody. Patients with presence of HCV antibody are eligible if HCV RNA is undetectable (<15 IU/mL).
- Major surgery within 4 weeks of the first dose of study drug
See the full eligibility criteria
Who can join
- ≥ 18 years of age at the time of informed consent
- Adequate organ function defined as: a. Absolute neutrophil count (ANC) > 750/mm3 (without growth factor support within 7 days) b. Platelet > 50,000/mm3 (without growth factor support or transfusion within 7 days) c. Creatinine clearance ≥ 30 mL/min (as estimated by the CockcroftGault or MDRD equation or as measured by nuclear medicine scan or 24hour urine collection) d. Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase, and alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase ≤ 3.0 × upper limit of normal (ULN) e. Serum total bilirubin < 2.0 × ULN (unless documented Gilbert's syndrome)
- 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, or 18 months after the last dose of obinutuzumab, whichever is longer. Highly effective contraceptive methods include the following: a. Combined (estrogen and progestogen containing) hormonal contraception associated with the inhibition of ovulation - Oral, intravaginal or transdermal b. Progestogen-only hormonal contraception associated with the inhibition of ovulation - Oral, injectable, implantable c. An intrauterine device d. Intrauterine hormone-releasing system e. Bilateral tubal occlusion f. Vasectomized partner g. Sexual abstinence (defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatment, starting the day prior to first dose of study drug, for the duration of the study, and for ≥ 90 days after the last dose of zanubrutinib, or 18 months after the last dose of obinutuzumab, whichever is longer). Total sexual abstinence should only be used as a contraceptive method if it is in line with the patients' usual and preferred lifestyle. Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of exposure to investigational medicinal product, and withdrawal are not acceptable methods of contraception. Of note, barrier contraception (including male and female condoms with or without spermicide) is not considered a highly effective method of contraception and if used, this method must be used in combination with another acceptable method listed above. For patients using hormonal contraceptives such as birth control pills or devices, a second barrier method of contraception (eg, condoms) must be used.
- Male patients if abstinent (as defined above), are eligible if vasectomized or if they agree to the use of barrier contraception in combination with other methods described above during the study treatment period and for ≥ 90 days after the last dose of zanubrutinib or 18 months after the last dose of obinutuzumab, whichever is longer.
- Ability to provide written informed consent and can understand and comply with the requirements of the study.
- Histologically confirmed diagnosis of B-cell follicular lymphoma (grade 1, 2 or 3a) based on the WHO 2008 classification of tumors of hematopoietic and lymphoid tissue
- ≥ 2 prior systemic treatments for follicular lymphoma
- Previously received an anti-CD20 antibody and an appropriate alkylator-based combination therapy, including a.Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone b.Rituximab, cyclophosphamide, vincristine, and prednisolone c.Bendamustine plus rituximab
- Disease progression after completion of most recent therapy or refractory disease, defined as failure to achieve CR or PR to most recent therapy, and most recent therapy was an appropriate second-line (or later) systemic therapy for follicular lymphoma
- Presence of measurable disease, defined as ≥ 1 nodal lesion that is > 2 cm in longest diameter, or ≥ 1 extranodal lesion that is > 1 cm in longest diameter
- Availability of archival tissue confirming diagnosis of B-cell follicular lymphoma (or if archival tissue is not available, a copy of the pathology report confirming diagnosis of B-cell follicular lymphoma is required)
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
- Life expectancy ≥ 6 months
What rules you out
- Known central nervous system involvement by leukemia or lymphoma
- 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
- Active fungal, bacterial and/or viral infection requiring systemic therapy
- Underlying medical conditions that, in the investigator's opinion, will render the administration of study drug hazardous or obscure the interpretation of safety or efficacy results
- Known infection with HIV, or serologic status reflecting active hepatitis B or C infection as follows: a. Presence of hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb). Patients with presence of HBcAb, but absence of HBsAg, are eligible if hepatitis B virus (HBV) DNA is undetectable (< 20 IU/mL), and if they are willing to undergo monthly monitoring for HBV reactivation. b. Presence of hepatitis C virus (HCV) antibody. Patients with presence of HCV antibody are eligible if HCV RNA is undetectable (<15 IU/mL).
- Major surgery within 4 weeks of the first dose of study drug
- Pregnant or lactating women
- Vaccination with a live vaccine within 35 days prior to the first dose of study drug
- Ongoing alcohol or drug addiction
- Hypersensitivity to zanubrutinib or obinutuzumab or any of the other ingredients of the study drugs
- Requires ongoing treatment with a strong CYP3A inhibitor or inducer
- Evidence of transformation from follicular lymphoma to DLBCL or other aggressive histology (such as large cells seen on biopsy or high PET avidity in a single node seen on PET scan)
- Concurrent participation in another therapeutic clinical trial.
- 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.
- Allogeneic hematopoietic stem cell transplantation within 12 months of study enrollment
- Prior exposure to a BTK inhibitor
- Prior malignancy within the past 2 years, except for curatively treated basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast, or localized Gleason score 6 prostate cancer.
- Clinically significant cardiovascular disease including the following: a. Myocardial infarction within 6 months before screening b. Unstable angina within 3 months before screening c. New York Heart Association Class III or IV congestive heart failure (see Appendix 4) d. History of clinically significant arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes) e. QTcF > 480 milliseconds based on Fridericia's formula f. History of Mobitz II second-degree or third degree heart block without a permanent pacemaker in place g. Uncontrolled hypertension as indicated by a minimum of 2 consecutive blood pressure measurements showing systolic blood pressure > 170 mmHg and diastolic blood pressure > 105 mmHg at screening
- History of severe bleeding disorder such as hemophilia A, hemophilia B, von Willebrand disease, or history of spontaneous bleeding requiring blood transfusion or other medical intervention
- History of stroke or intracranial hemorrhage within 6 months before first dose of study drug
- Severe or debilitating pulmonary disease
The study team makes the final eligibility decision.
Where it's taking place
- Canada
- United Kingdom
- Russian Federation
- China
- New Zealand
- United States
- Taiwan
- Australia
- Belarus
- Korea, Republic of
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 65+ years, 18-64 years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Canada; United Kingdom; Russian Federation; China; New Zealand; United States and 4 more location(s). Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.