Follicular Lymphoma ( FL)Phase 3NCT07719855
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
A Phase 3 study testing Orelabrutinib, obinutuzumab and Lenalidomide in people with Follicular Lymphoma ( FL), run by Ruijin Hospital at 1 site in China.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Follicular Lymphoma ( FL)
- What is being tested?
- Orelabrutinib, obinutuzumab and Lenalidomide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 652 participants
- Where
- 1 siteChina
- Study dates
- Jul 2026to Dec 2033
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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)
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
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)
- Being tested
- Orelabrutinib, obinutuzumab, Lenalidomide, Cyclophosphamide, Doxorubicin
- Keywords
- Follicular Lymphoma
- Medical subject headings
- Lymphoma, Follicular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OrelabrutinibDrug
Orelabrutinib PO will be administered as per the schedule specified in the respective arm.
obinutuzumabDrug
Obinutuzumab IV infusion will be administered as per the schedule specified in the respective arm.
LenalidomideDrug
Lenalidomide PO will be administered as per the schedule specified in the respective arm.
CyclophosphamideDrug
Cyclophosphamide IV infusion will be administered as per the schedule specified in the respective arm.
DoxorubicinDrug
Doxorubicin IV infusion will be administered as per the schedule specified in the respective arm.
PrednisoneDrug
Prednisone PO will be administered as per the schedule specified in the respective arm.
VincristineDrug
Vincristine infusion will be administered as per the schedule specified in the respective arm.
BendamustineDrug
Bendamustine infusion will be administered as per the schedule specified in the respective arm.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: obinutuzumab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Prednisone; Drug: Vincristine; Drug: Bendamustine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
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)
Measured: End of treatment visit (6-8 weeks after last dose on Day 1 of Cycle 6 [Cycle length=21 days]
Objective response rate
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)
Measured: End of treatment visit (6-8 weeks after last dose on Day 1 of Cycle 6 [Cycle length=21 days]
Overall survival
OS defined as the time from diagnosis to death from any cause
Measured: up to approximately 6 years
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v6.0
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v6.0
Measured: From enrollment to study completion, a maximum of 6 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2026
- Study startJul 2026 (estimated)
- Primary completionJul 2030 (estimated)
- Study completionDec 2033 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Follicular Lymphoma ( FL)Studies of the same condition, open and under way.
- More trials run by Ruijin HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 652 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ruijin Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Zhao Weili, Ruijin Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07719855
- Sponsor's protocol ID
- Future
- Status last verified
- Jul 2026
- First submitted
- 10 Jul 2026
- Last updated
- 22 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No