A Multicenter, Prospective, Open-Label, Randomized Controlled Clinical Study of Orelabrutinib Combined With Obinutuzumab and Lenalidomide Versus Obinutuzumab Plus Chemotherapy for Treatment-Naive Follicular Lymphoma

Обзор

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).

Вмешательства

• Препарат Orelabrutinib
  Orelabrutinib PO will be administered as per the schedule specified in the respective arm.
• Препарат obinutuzumab
  Obinutuzumab IV infusion will be administered as per the schedule specified in the respective arm.
• Препарат Lenalidomide
  Lenalidomide PO will be administered as per the schedule specified in the respective arm.
• Препарат Cyclophosphamide
  Cyclophosphamide IV infusion will be administered as per the schedule specified in the respective arm.
• Препарат Doxorubicin
  Doxorubicin IV infusion will be administered as per the schedule specified in the respective arm.
• Препарат Prednisone
  Prednisone PO will be administered as per the schedule specified in the respective arm.
• Препарат Vincristine
  Vincristine infusion will be administered as per the schedule specified in the respective arm.
• Препарат Bendamustine
  Bendamustine infusion will be administered as per the schedule specified in the respective arm.

Первичные конечные точки

• Progression-free survival [Срок оценки: From enrollment to the first occurrence of disease progression or relapse, or death from any cause, whichever occurs earlier (a maximum of 6 years)]

Вторичные конечные точки (4)

• Complete response rate [Срок оценки: End of treatment visit (6-8 weeks after last dose on Day 1 of Cycle 6 [Cycle length=21 days]]
• Objective response rate [Срок оценки: End of treatment visit (6-8 weeks after last dose on Day 1 of Cycle 6 [Cycle length=21 days]]
• Overall survival [Срок оценки: up to approximately 6 years]
• Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v6.0 [Срок оценки: From enrollment to study completion, a maximum of 6 years]

Критерии участия

Критерии включения

• Subjects with histopathologically confirmed follicular lymphoma (FL) Grade 1-3A;
• Subjects who have never received prior anti-lymphoma therapy;
• Age ≥ 18 years old;
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2;
• Adequate bone marrow, hepatic and renal function, defined as:

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.

Критерии исключения

• Uncontrolled cardiovascular and cerebrovascular diseases, coagulation disorders, connective tissue diseases, severe infectious diseases, etc.
• Abnormal laboratory parameters at screening (unless attributed to follicular lymphoma):

• Absolute neutrophil count < 1.5 × 10⁹/L
• Platelet count < 80 × 10⁹/L; if bone marrow involvement is present, platelet count < 50 × 10⁹/L
• Alanine transaminase (ALT) or aspartate transaminase (AST) > 2 × upper limit of normal (ULN); alkaline phosphatase (AKP) or bilirubin > 1.5 × ULN
• Serum creatinine > 1.5 × ULN OR estimated glomerular filtration rate (eGFR) < 40 mL/min/1.73 m² (calculated via the Cockcroft-Gault equation or Modification of Diet in Renal Disease \[MDRD\] equation)
• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Ruijin Hosiptal — Шанхай

Идентификаторы

NCT: NCT07719855 · Future

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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