Orelabrutinib plus rituximab followed by orelabrutinib maintenance for relapsed or refractory follicular lymphoma

Orelabrutinib Plus Rituximab Followed by Maintenance With Orelabrutinib for Relapsed and Refractory Follicular Lymphoma(RR FL) ：a Single Arm, Open Label, Multi-center Phase II Study

This trial tests whether combining orelabrutinib with rituximab, followed by orelabrutinib alone, helps people whose follicular lymphoma has come back or stopped responding.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 32 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Sun Yat-sen University (Academic / other)
• Drugs / interventions: ibrutinib, chemotherapy, radiation, rituximab, orelabrutinib
• Locations: 3 sites (Guangzhou, Guangdong and 2 other locations)
• Trial ID: NCT04989621 on ClinicalTrials.gov

What this trial studies

This is a phase 2 interventional trial testing a treatment sequence of orelabrutinib combined with rituximab followed by maintenance orelabrutinib in adults with relapsed or refractory follicular lymphoma. Patients must have histologically confirmed grade 1, 2, or 3A disease, prior anti-lymphoma therapy, at least one measurable lesion by 2014 Lugano criteria, and ECOG performance status 0-2. Key exclusions include prior BTK inhibitor therapy, histologic transformation, CNS lymphoma, recent stroke or intracranial hemorrhage, and need for warfarin. The trial will monitor response rates and safety during combination therapy and the subsequent maintenance phase.

Who should consider this trial

Good fit: Adults (18+) with histologically confirmed grade 1–3A follicular lymphoma who have received prior anti-lymphoma treatment, have at least one measurable lesion, ECOG 0–2, and have not received prior BTK inhibitors are ideal candidates.

Not a fit: Patients with histologic transformation, known CNS lymphoma, prior BTK inhibitor exposure, recent stroke or intracranial hemorrhage, or who require warfarin are unlikely to be eligible or to benefit from this protocol.

Why it matters

Potential benefit: If effective, this regimen could deepen or extend responses and delay disease progression for people with relapsed or refractory follicular lymphoma.

How similar studies have performed: Other BTK inhibitors combined with anti-CD20 antibodies have shown activity in some B‑cell lymphomas but results in follicular lymphoma have been mixed, and orelabrutinib is a newer, more selective BTK inhibitor with limited published data in this setting.

Eligibility criteria

Inclusion Criteria:

* Histologically confirmed grade 1, 2, or 3A FL;
* Patients received prior anti-lymphoma treatment;
* At least one evaluable lesion according to 2014 Lugano criteria;
* Age 18 years or older;
* Eastern Cooperative Oncology Group (ECOG) of 0-2;
* Life expectancy \> 3 months;
* Able to participate in all required study procedures;
* Proper functioning of the major organs:

Exclusion Criteria:

* Patients who required warfarin or had a history of stroke or intracranial hemorrhage within 6 months, active transformed disease;
* Histological transformation of follicular lymphoma;
* Known central nervous system lymphoma;
* Received a prior allogeneic hematopoietic stem cell transplant. Prior autologous hematopoietic stem cell transplant is allowed;
* Subjects who have received prior treatment with ibrutinib, or other BTK inhibitors;
* Uncontrolled active infection, with the exception of tumor-related B symptom fever;
* Prior nitrosoureas within 6 weeks, chemotherapy within 3 weeks, therapeutic anticancer antibodies within 4 weeks, radio- or toxin-immunoconjugates within 10 weeks, radiation therapy or other investigational agents within 3 weeks, or major surgery within 4 weeks of first dose of study drug;
* Subjects who progressed or become refractory while on treatment with PI3K inhibitors are excluded. However, subjects who were responding to PI3K inhibitors, but had treatment discontinued due to toxicity, are eligible;
* Patients require treatment with strong CYP3A inhibitors;
* Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of Screening;
* Patients with active hepatitis B or active hepatitis C. Patients who are positive for hepatitis B Surface Antigen (HBsAg) or hepatitis C Virus (HCV) antibodies at screening stage must pass further detection of hepatitis B Virus (HBV) DNA (no more than 1000 IU/mL) and HCV RNA (no more than the lower limit of the detection method) in the row. Hepatitis B carriers, stable hepatitis B (DNA titer should not be higher than 1000 IU/mL) after drug treatment, and cured hepatitis C patients can be enrolled in the group;

Where this trial is running

Guangzhou, Guangdong and 2 other locations

• Guangdong General Hospital — Guangzhou, Guangdong, China (Recruiting)
• Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, — Guangzhou, Guangdong, China (Not_yet_recruiting)
• Sun Yat-sen Universitiy Cancer Center, Sun Yat-Sen University, — Guangzhou, Guangdong, China (Recruiting)

Study contacts

• Study coordinator: Qingqing Cai

Conditions Follicular Lymphoma; Relapsed and Refractory Follicular Lymphoma