Follicular Lymphoma ( FL)
Conditions
Keywords
Follicular Lymphoma
Brief summary
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).
Interventions
DRUGOrelabrutinib
Orelabrutinib PO will be administered as per the schedule specified in the respective arm.
DRUGobinutuzumab
Obinutuzumab IV infusion will be administered as per the schedule specified in the respective arm.
DRUGLenalidomide
Lenalidomide PO will be administered as per the schedule specified in the respective arm.
DRUGCyclophosphamide
Cyclophosphamide IV infusion will be administered as per the schedule specified in the respective arm.
DRUGDoxorubicin
Doxorubicin IV infusion will be administered as per the schedule specified in the respective arm.
DRUGPrednisone
Prednisone PO will be administered as per the schedule specified in the respective arm.
DRUGVincristine
Vincristine infusion will be administered as per the schedule specified in the respective arm.
DRUGBendamustine
Bendamustine infusion will be administered as per the schedule specified in the respective arm.
Sponsors
Ruijin Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subjects with histopathologically confirmed follicular lymphoma (FL) Grade 1-3A; 2. Subjects who have never received prior anti-lymphoma therapy; 3. Age ≥ 18 years old; 4. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2; 5. 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.
Exclusion criteria
1. Uncontrolled cardiovascular and cerebrovascular diseases, coagulation disorders, connective tissue diseases, severe infectious diseases, etc. 2. Abnormal laboratory parameters at screening (unless attributed to follicular lymphoma): 1. Absolute neutrophil count \< 1.5 × 10⁹/L 2. Platelet count \< 80 × 10⁹/L; if bone marrow involvement is present, platelet count \< 50 × 10⁹/L 3. Alanine transaminase (ALT) or aspartate transaminase (AST) \> 2 × upper limit of normal (ULN); alkaline phosphatase (AKP) or bilirubin \> 1.5 × ULN 4. 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) 3. Human immunodeficiency virus (HIV)-positive subjects. 4. Left ventricular ejection fraction (LVEF) \< 50%. 5. 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. 6. Receiving concurrent anti-tumor therapy (for lymphoma or other malignancies). 7. Subjects with psychiatric disorders, or those with known/suspected poor compliance to the study protocol. 8. 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. 9. History of stroke or intracranial hemorrhage within 6 months before the first dose of study drug. 10. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival | From enrollment to the first occurrence of disease progression or relapse, or death from any cause, whichever occurs earlier (a maximum of 6 years) | PFS, defined as the time from diagnosis to the first occurrence of disease progression or relapse using the 2014 Lugano Response Criteria or death due to any cause, whichever occurs first; as determined by the investigator |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete response rate | End of treatment visit (6-8 weeks after last dose on Day 1 of Cycle 6 [Cycle length=21 days] | CR rate at the end of treatment by FDG-PET defined as the proportion of participants with CR at the end of treatment according to the 2014 Lugano Response Criteria; as determined by the investigator and IRC (separately) |
| Objective response rate | End of treatment visit (6-8 weeks after last dose on Day 1 of Cycle 6 [Cycle length=21 days] | ORR at treatment completion or discontinuation defined as the proportion of participants with CR or partial response (PR) at the end of treatment according to the 2014 Lugano Response Criteria; as determined by the investigator and IRC(separately) |
| Overall survival | up to approximately 6 years | OS defined as the time from diagnosis to death from any cause |
| Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v6.0 | From enrollment to study completion, a maximum of 6 years | Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v6.0 |
Countries
China
Contacts
CONTACTPeng-Peng Xu
Outcome results
None listed