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

NCT07719855 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: Future
• Study Type: interventional
• Target: 652
• Locations: 1 country
• Sites: 1

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).

Conditions

Follicular Lymphoma ( FL)

Keywords

Follicular Lymphoma

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  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

  From enrollment to the first occurrence of disease progression or relapse, or death from any cause, whichever occurs earlier (a maximum of 6 years)

Secondary Outcomes (4)

• Complete response rate

  End of treatment visit (6-8 weeks after last dose on Day 1 of Cycle 6 [Cycle length=21 days]

• Objective response rate

  End of treatment visit (6-8 weeks after last dose on Day 1 of Cycle 6 [Cycle length=21 days]

• Overall survival

  up to approximately 6 years

• Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v6.0

  From enrollment to study completion, a maximum of 6 years

Study Arms (2)

RO2

EXPERIMENTAL

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.

Drug: Orelabrutinib; Drug: obinutuzumab; Drug: Lenalidomide

O-Chemo

ACTIVE COMPARATOR

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.

Drug: obinutuzumab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Prednisone; Drug: Vincristine; Drug: Bendamustine

Interventions

Orelabrutinib DRUG

Orelabrutinib PO will be administered as per the schedule specified in the respective arm.

RO2

obinutuzumab DRUG

Obinutuzumab IV infusion will be administered as per the schedule specified in the respective arm.

O-Chemo; RO2

Lenalidomide DRUG

Lenalidomide PO will be administered as per the schedule specified in the respective arm.

RO2

Vincristine DRUG

Vincristine infusion will be administered as per the schedule specified in the respective arm.

O-Chemo

Bendamustine DRUG

Bendamustine infusion will be administered as per the schedule specified in the respective arm.

O-Chemo

Cyclophosphamide DRUG

Cyclophosphamide IV infusion will be administered as per the schedule specified in the respective arm.

O-Chemo

Doxorubicin DRUG

Doxorubicin IV infusion will be administered as per the schedule specified in the respective arm.

O-Chemo

Prednisone DRUG

Prednisone PO will be administered as per the schedule specified in the respective arm.

O-Chemo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• ）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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ruijin Hospital: lead

Study Sites (1)

Ruijin Hosiptal

Shanghai, Shanghai Municipality, 20025, China

Location

MeSH Terms

Conditions

Lymphoma, Follicular

Interventions

orelabrutinib; obinutuzumab; Lenalidomide; Cyclophosphamide; Doxorubicin; Prednisone; Vincristine; Bendamustine Hydrochloride

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines; Butyrates; Acids, Acyclic; Benzimidazoles

Central Study Contacts

Peng-Peng Xu

CONTACT

+862164370045 Ext. 610707; pengpeng_xu@126.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice President, Ruijin Hospital

Study Record Dates

• First Submitted: July 10, 2026
• First Posted: July 22, 2026
• Study Start: July 1, 2026
• Primary Completion (Estimated): July 1, 2030
• Study Completion (Estimated): December 1, 2033
• Last Updated: July 22, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)