Comparing 3 approaches for large b-cell lymphoma

Exclusion

• −Prior anaphylactic reaction to monoclonal antibody therapy at any time prior to enrollmentEnrolmentThe number of participants a study plans to include, or has included.Read more →
• −Hypersensitivity to zanubrutinib and Tislelizumab or any of the other ingredients of the applicable study drugs
• −Serologic status reflecting active viral hepatitis B or C infection as follows:
• −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 (\< 20IU), and if they are willing to be on appropriate prophylaxis and undergo monitoring for HBV reactivation if clinically indicated.
• −Presence of hepatitis C virus (HCV) antibody. Patients with presence of HCV antibody are eligible if HCV RNA is undetectable.
• −Individuals with known active HIV infection are eligible if CD4 and viral titres are controlled
• −Active autoimmune diseases or history of severe autoimmune diseases; these include but are not limited to a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis, systemic lupus erythematosus, rheumatoid arthritis, connective tissue diseases, scleroderma, inflammatory bowel disease, Crohn's disease, ulcerative colitis, autoimmune hepatitis, toxic epidermal necrolysis, Stevens-Johnson syndrome, or clinically manifest antiphospholipid syndrome. Note: Subjects are permitted to enroll if they have vitiligo, eczema, type I diabetes mellitus, or endocrine deficiencies, including thyroiditis managed with replacement hormones including physiologic doses of corticosteroids. Subjects with Sjögren's syndrome and psoriasis controlled with topical medication and subjects with positive serology, such as antinuclear antibodies or antithyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible.
• −Life expectancy \< 30 days at the time of enrollment
• −Prior exposure to BTK or PD-1 inhibitor at any time prior to enrollment
• −Intervention armArmOne of the groups in a study, each receiving something different.Read more →: On higher than physiologic doses (10mg daily) of prednisone daily at least 7 days prior to initiation of trial treatment. SOCStandard of careThe treatment normally given for a condition outside a study.Read more → arm: On prednisone for symptom management only.
• −Uncontrolled autoimmune disease
• −Known active CNS involvement disease
• −History of prior allogeneic transplant or organ transplant
• −Active bleeding or history of bleeding diathesis including, but not limited to,
• −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 180 days before first dose of study drug
• −Difficulty with or unable to swallow oral medication, or known conditions that would significantly affect gastrointestinal function that would limit absorption of oral medication
• −History of chronic or active, uncontrolled bacterial, viral or fungal infection; human T-cell lymphotropic virus type 1 seropositive status.
• −Any serious intercurrent illness, life threatening condition, organ system dysfunction including:
• −(1) Clinically significant cardiovascular including:
• −prolonged QTc \> 480ms,
• −history of Mobitz II second degree or third degree heart block without a permanent pacemaker in situ,
• −uncontrolled hypertension as indicated by a minimum of 2 consecutive blood pressure reading on 2 separate occasions showing systolic BP \> 170 mmHg and/or diastolic BP \> 105mmHg at screeningScreeningThe checks done before joining, to see whether a study fits.Read more →,
• −uncontrolled or history of symptomatic arrhythmias (ie. sustained ventricular tachycardia, ventricular fibrillation, Torsades de Pointes),
• −congestive heart failure or NYHA class ≥ 3,
• −myocardial infarction within 6 months prior to enrollment;
• −(2) History of significant cerebrovascular events including stroke or intracranial hemorrhage within 6 months prior to enrollment
• −Vaccination with a live vaccine within 28 days prior to the first dose of study drug
• −Patient requires treatment with warfarin or other vitamin K antagonists
• −Severe or debilitating pulmonary disease (dyspnea at rest, significant shortness of breath, congestive obstructive pulmonary disease).
• −Active and symptomatic fungal, bacterial, and/or viral infection; human T-cell lymphotropic virus type 1 seropositive status.
• −Any illness or condition that in the opinion of the investigatorPrincipal investigatorThe doctor or researcher responsible for running the study at a site.Read more → may affect safety of treatment or evaluation of any study endpointEndpointThe specific thing a study measures to answer its question.Read more →.
• −A condition requiring systemic treatment with either corticosteroids (\> 20 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days of study drug administration, except for PCNSL and SCNSL. Note: adrenal replacement doses ≤ 20 mg daily prednisone or equivalents are permitted in the absence of active autoimmune disease; subjects are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption).
• −Patients with contraindications for zanubrutinib and Tislelizumab
• −Patients with toxicities (as a result of prior anticancer therapy) which have not recovered to baselineBaselineYour starting measurements, taken before treatment begins.Read more → or stabilized, except for AEs not constituting a likely safety risk
• −With uncontrolled diabetes or \> Grade 1 laboratory test abnormalities in potassium, sodium, or corrected calcium despite standard medical management or ≥ Grade 3 hypoalbuminemia ≤ 14 days before randomizationRandomisedWhich group you go into is decided by chance, not by you or your doctor.Read more →.
• −Female patients of childbearing potential must practice highly effective methods (Section 6.7.1.1) of contraception initiated prior to first dose of study drug, for the duration of the study, and for ≥ 120 days after the last dose of zanubrutinib or tislelizumab
• −Male patients are eligible if vasectomized or if they agree to the use of barrier contraception with highly effective methods during the study treatment period and for ≥ 120 days after the last dose of zanubrutinib or tislelizumab.
• −Pregnant or lactating women.
• −History of other active malignancies within 2 years prior to enrollment, with the exception of adequately treated in-situ carcinoma of cervix; localized basal cell or squamous cell carcinoma of skin; or previous malignancy confined and treated locally (surgery or other modality) with curative intent.
• −Major surgery within 4 weeks of the first dose of study drug
• −History of interstitial lung disease or non-infectious pneumonitis or pulmonary fibrosis, except for those induced by radiation therapy.
• −Major surgery in the past 4 weeks prior to the first day of screening.