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

July 19, 2026 updated by: Zhao Weili, Ruijin Hospital
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).

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

652

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Shanghai Municipality
      • Shanghai, Shanghai Municipality, China, 20025
        • Ruijin Hosiptal

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: RO2

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: Lenalidomide
Lenalidomide PO will be administered as per the schedule specified in the respective arm.
Drug: Orelabrutinib
Orelabrutinib PO will be administered as per the schedule specified in the respective arm.
Drug: obinutuzumab
Obinutuzumab IV infusion will be administered as per the schedule specified in the respective arm.
Active Comparator: O-Chemo

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: Cyclophosphamide
Cyclophosphamide IV infusion will be administered as per the schedule specified in the respective arm.
Drug: Doxorubicin
Doxorubicin IV infusion will be administered as per the schedule specified in the respective arm.
Drug: Prednisone
Prednisone PO will be administered as per the schedule specified in the respective arm.
Drug: obinutuzumab
Obinutuzumab IV infusion will be administered as per the schedule specified in the respective arm.
Drug: Vincristine
Vincristine infusion will be administered as per the schedule specified in the respective arm.
Drug: Bendamustine
Bendamustine infusion will be administered as per the schedule specified in the respective arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival
Time Frame: 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
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete response rate
Time Frame: 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)
End of treatment visit (6-8 weeks after last dose on Day 1 of Cycle 6 [Cycle length=21 days]
Objective response rate
Time Frame: 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)
End of treatment visit (6-8 weeks after last dose on Day 1 of Cycle 6 [Cycle length=21 days]
Overall survival
Time Frame: up to approximately 6 years
OS defined as the time from diagnosis to death from any cause
up to approximately 6 years
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v6.0
Time Frame: From enrollment to study completion, a maximum of 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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ruijin Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

July 1, 2026

Primary Completion (Estimated)

July 1, 2030

Study Completion (Estimated)

December 1, 2033

Study Registration Dates

First Submitted

July 10, 2026

First Submitted That Met QC Criteria

July 19, 2026

First Posted (Actual)

July 22, 2026

Study Record Updates

Last Update Posted (Actual)

July 22, 2026

Last Update Submitted That Met QC Criteria

July 19, 2026

Last Verified

July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Future

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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