This study intends to conduct a prospective, multicenter, open-label, randomized controlled clinical trial to systematically evaluate the efficacy and safety of the orelabrutinib plus obinutuzumab and lenalidomide (RO2) regimen versus the obinutuzumab-combined chemotherapy (O-chemo) regimen in patients with previously untreated follicular lymphoma. The primary observation is whether the RO2 regimen can maintain or improve therapeutic efficacy while significantly reducing hematological toxicities and other related adverse reactions, so as to provide a novel therapeutic option for improving the prognosis and quality of life of patients with follicular lymphoma (FL).
Inclusion Criteria:
1)Absolute neutrophil count (ANC) > 1,000/μL; platelet count > 50,000/mm³; hemoglobin > 80 g/dL; 2)Alanine transaminase (ALT) and aspartate transaminase (AST) < 3 × upper limit of normal (ULN); 3)Total serum bilirubin < 1.5 × ULN (patients with Gilbert syndrome are eligible); serum creatinine < 2 × ULN OR creatinine clearance > 50 mL/min; 6、Tumor tissue available for testing (fresh tissue preferred; archived paraffin-embedded tissue is acceptable); 7、Women of childbearing potential with a negative pregnancy test prior to Day 1 of treatment, who agree to use effective contraception throughout the study period and for at least 1 year after completion of study treatment; 8、Written informed consent obtained from the subject or their legal authorized representative prior to any study-specific examinations or procedures.
Exclusion Criteria:
Uncontrolled cardiovascular and cerebrovascular diseases, coagulation disorders, connective tissue diseases, severe infectious diseases, etc.
Abnormal laboratory parameters at screening (unless attributed to follicular lymphoma):
Human immunodeficiency virus (HIV)-positive subjects.
Left ventricular ejection fraction (LVEF) < 50%.
HBV screening requirements: Subjects with positive hepatitis B surface antigen (HBsAg) must undergo HBV DNA testing; those with HBV DNA < 10³ IU/mL are eligible for enrollment. Subjects with negative HBsAg but positive hepatitis B core antibody (HBcAb) (regardless of hepatitis B surface antibody [HBsAb] status) must also undergo HBV DNA testing; those with HBV DNA < 10³ IU/mL are eligible for enrollment.
Receiving concurrent anti-tumor therapy (for lymphoma or other malignancies).
Subjects with psychiatric disorders, or those with known/suspected poor compliance to the study protocol.
Requiring continuous treatment with strong or moderate CYP3A inhibitors or CYP3A inducers (see Appendix 3). Subjects who have taken strong/moderate CYP3A inhibitors or inducers within 7 days prior to the first dose of study drug (or within less than 5 half-lives of such medications) are excluded.
History of stroke or intracranial hemorrhage within 6 months before the first dose of study drug.
Inability to swallow capsules, or presence of diseases that significantly impair gastrointestinal function, such as malabsorption syndrome, bariatric surgery, inflammatory bowel disease, partial or complete intestinal obstruction.
Other uncontrolled concomitant medical conditions deemed by the investigator to interfere with study participation. Any life-threatening disease, medical condition or organ dysfunction that may compromise subject safety, interfere with the absorption or metabolism of oral targeted agents, or expose study outcomes to excessive risk, as judged by the investigator.
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Patients in the study group will receive six cycles of the RO2 regimen, with each cycle repeated every 21 days. Routine efficacy assessments will be performed upon completion of each cycle during treatment. PET-CT scanning will be used for efficacy evaluation after three cycles of therapy. Patients with stable disease (SD) or progressive disease (PD) will discontinue study treatment, and the investigator will determine the salvage therapy regimen. Patients achieving a complete response (CR) or partial response (PR) will continue the original regimen for cycles 4 to 6. After completion of six cycles of treatment, PET-CT will be conducted for efficacy reassessment. Patients with CR or PR will finish induction therapy and enter the maintenance phase. The study group will receive obinutuzumab maintenance therapy once every three months for a total of two years, combined with lenalidomide maintenance administered for 10 days per month over six months.
Patients in the study group will receive six cycles of the O-chemo regimen, with each cycle repeated every 21 days. Routine efficacy assessments will be performed upon completion of each cycle during treatment. PET-CT scanning will be used for efficacy evaluation after three cycles of therapy. Patients with stable disease (SD) or progressive disease (PD) will discontinue study treatment, and the investigator will determine the salvage therapy regimen. Patients achieving a complete response (CR) or partial response (PR) will continue the original regimen for cycles 4 to 6. After completion of six cycles of treatment, PET-CT will be conducted for efficacy reassessment. Patients with CR or PR will finish induction therapy and enter the maintenance phase. The study group will receive obinutuzumab maintenance therapy once every three months for a total of two years.
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Orelabrutinib Combined With Pola-R-CHP Regimen for the Treatment of Untreated Non-GCB Diffuse Large B-Cell Lymphoma
A Study of Orelabrutinib Plus R-CHOP in Treatment-naïve Patients With MCD Subtype Diffuse Large B-cell Lymphoma
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Orelabrutinib Combined With Obinutuzumab and Lenalidomide (OGL Regimen) as First-line Treatment for Marginal Zone Lymphoma.