Follicular LymphomaPhase 2NCT06350318
Rituximab and Zanubrutinib in Patients With Indolent B-cell Lymphomas
A Phase 2 study testing Zanubrutinib and Rituximab in people with Follicular Lymphoma and Marginal Zone Lymphoma, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.
Trial summary
The purpose of the study is to establish the safety and efficacy of zanubrutinib in combination with rituximab for people with untreated B-cell lymphomas (marginal zone lymphoma and follicular lymphomas). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Follicular Lymphoma, Marginal Zone Lymphoma, B-Cell Lymphoma
- What is being tested?
- Zanubrutinib and Rituximab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Apr 2024to Mar 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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
- Cohort A: Previously untreated MZL. Prior therapy with H. Pylori antibiotic therapy or hepatitis C antiviral therapy are allowed on Cohort A.
- Cohort B: Previously untreated FL
- Pathological confirmation of lymphoma: availability of archival tissue confirming diagnosis of MZL (cohort A) or FL (cohort B). Availability of formalin-fixed, paraffin-embedded (FFPE) archival tumor specimens from within past 18 months from screening and pathological diagnosis confirmed by a pathologist at the participating site or willingness of the participant to undergo a fresh tumor biopsy if adequate archival tissue not available is required. This includes:
- MZL (Cohort A):
- Nodal MZL requiring systemic therapy
- Splenic MZL requiring systemic therapy
Show all 25Show fewer
- Extra-nodal marginal zone lymphoma:
- Non-gastric/non-cutaneous MZL requiring systemic therapy.
- Cutaneous MZL will be eligible only if they have pathologically confirmed extra-cutaneous disease.
- Gastric MZL only if advanced stage disease requiring systemic therapy (e.g., stage IIE, II2, IV- supradiaphragmatic nodal or disseminated extranodal disease such as bone marrow or additional extra nodal sites.
- FL (Cohort B):
- Pathological grade 1, 2, or 3a based on the World Health Organization (WHO 2008) classification of tumors of hematopoietic and lymphoid tissue.
- 1. Please note, grade 3B are excluded.
- All participants must have disease requiring systemic therapy rather than local radiation (ie, stage II only if not eligible for radiation therapy or with stage III/IV).
- All participants should have measurable disease. Measurable disease is defined as a lymph node or tumor mass that is ≥ 1.5 cm in at least one dimension by CT or the CT portion of the PET/CT.
- Documentation of CD20+ status.
- All participants must have an indication for therapy such as: symptoms attributable to lymphoma, threatened end-organ function, or cytopenia secondary to lymphoma.
- All participants must be 18 years of age or older.
- All participants must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.
- All participants must be able to swallow whole pills.
- All participants must have the ability and willingness to comply with the requirements of the study protocol.
- All female participants who are of non-reproductive potential (i.e., post-menopausal by history - no menses for ≥1 year; OR history of hysterectomy; OR history of bilateral tubal ligation; OR history of bilateral oophorectomy).
- All female participants of childbearing potential must have a negative serum pregnancy test upon study entry.
- All male and female participants of reproductive potential who agree to use both a highly effective method of birth control (e.g., implants, injectables, combined oral contraceptives, some intrauterine devices [IUDs], complete abstinence, or sterilized partner) and a barrier method (e.g., condoms, vaginal ring, sponge, etc) during the period of therapy. Female participants of reproductive potential who are not surgically sterile must practice adequate birth control for a minimum of 30 days after last dose of zanubrutinib or 12 months after last dose of rituximab, whichever is longer. Male participants are eligible if abstinent, vasectomized, or if they agree to the use of barrier contraception in combination with other methods described above during the study treatment period and for ≥ 30 days after the last dose of zanubrutinib, or 12 months after the last dose of rituximab, whichever is longer.
- All participants must have adequate organ function.
Who cannot join
- Prior therapy for lymphoma including chemotherapy or immunotherapy. Participant may have received corticosteroids but should be off them 5 days prior to study entry.
- Prior exposure to a BTK inhibitor.
- Known prior significant hypersensitivity to rituximab (not including infusion reactions).
- Prior history of malignancies unless the patient has been disease free for ≥ 2 years. Exceptions include basal cell carcinoma or squamous cell carcinoma of the skin; carcinoma in situ of cervix; carcinoma in situ of breast, localized prostate cancer, or superficial bladder cancer that has undergone curative therapy.
- Participants with evidence of large B cell transformation or other aggressive histology (such as large cells seen on biopsy or high PET avidity in a single node seen on PET scan) are not eligible.
- Known central nervous system (CNS) involvement by lymphoma.
Show all 22Show fewer
- Known bleeding disorders (e.g., von Willebrand's disease or hemophilia).
- Concomitant use of warfarin or other Vitamin K antagonists.
- Requires ongoing treatment with a moderate or strongCYP3A inhibitor or inducer.
- Known active bacterial, viral, fungal, mycobacterial, or other infection (excluding fungal infections of nail beds) or any major episode of infection requiring treatment with IV antibiotics or hospitalization (related to the completion of the course of antibiotics) within 4 weeks before the start of Cycle 1.
- Known infection with human immunodeficiency virus (HIV).
- Viral Hepatitis:
- Participants with active hepatitis B defined by hepatitis B surface antigen positivity or core antibody positivity in the presence of detectable serum hepatitis B DNA viremia are not eligible for this study.
- Participants with a positive hepatitis B core antibody but with negative hepatitis B DNA may be considered for participation, but must agree to receive appropriate hepatitis B antiviral therapy while on rituximab and have hepatitis B DNA monitored with real-time PCR by the treating physician. These patients should be referred to a hepatologist or gastroenterologist for appropriate monitoring and management.
- Hepatitis C: Patients with positive hepatitis C serology unless HCV RNA is confirmed negative by PCR.
- Vaccination with a live vaccine ≤ 28 days prior to the start of treatment.
- Participants should not have a history of uncontrolled seizures.
- Currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or Class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification; or a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to enrollment on the study.
- Uncontrolled hypertension as indicated by a minimum of 2 consecutive blood pressure measurements showing systolic blood pressure > 170 mmHg and diastolic blood pressure > 105 mmHg at screening.
- Participants should not have a stroke or intracranial hemorrhage within last 6 months.
- Participants may not have had major surgery within 28 days of enrollment, or minor surgery within 7 days of enrollment. Examples of minor surgery include dental surgery, insertion of a venous access device, skin biopsy, or aspiration of a joint. The decision about whether a surgery is major or minor can be made at the discretion of the treating physician.
- Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator's opinion, could compromise the subject's safety or put the study outcomes at undue risk.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Moffitt Cancer Center
Tampa, Florida, 33612
Richard Corona, 813-745-3465, Richard.Corona@moffitt.org
Sameh Gaballa, MD
About this study
Official title: A Phase 2 Open-Label, Multicenter Study of Rituximab and Zanubrutinib in Patients With Indolent B-cell Lymphomas
The purpose of the study is to establish the safety and efficacy of zanubrutinib in combination with rituximab for people with untreated B-cell lymphomas (marginal zone lymphoma and follicular lymphomas).
- Conditions
- Follicular Lymphoma, Marginal Zone Lymphoma, B-Cell Lymphoma
- Being tested
- Zanubrutinib, Rituximab
- Keywords
- B-Cell Lymphoma, Follicular Lymphoma, Marginal Zone Lymphoma
- Medical subject headings
- Lymphoma, Follicular, Lymphoma, B-Cell, Marginal Zone, Lymphoma, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZanubrutinibDrug
Also called Brukinsa
Zanubrutinib is an anti-cancer medication administered orally.
RituximabDrug
Also called Rituxin
Rituximab is a biologic medication administered intravenously or subcutaneously.
| Study group | Role | What they receive |
|---|---|---|
| Cohort A: Untreated Marginal Zone Lymphoma | Experimental | Rituximab (Standard of Care) will be administered for up to 6 cycles (28-day cycles).
Cycle 1: Days 1, 8, 15, and 22. Cycle 2-6: Day 1, every 28 days.
Rituximab: Intravenous rituximab formulations (IV rituximab or IV rituximab biosimilars will be administered by IV infusion at a dose of 375 mg/m2 per local institutional guidelines) or subcutaneous rituximab formulations (RITUXAN HYCELA) 1,400 mg/23,400 Units (1,400 mg rituximab and 23,400 Units hyaluronidase human) subcutaneously at a fixed dose per local institutional guidelines.
Zanubrutinib 320 mg will be administered orally once daily starting on day 1 of cycle 1.
Zanubrutinib will be continued once daily for up to 24 cycles or until disease progression or unacceptable toxicity occurs. Receives: Drug: Zanubrutinib; Drug: Rituximab |
| Cohort B: Untreated Follicular Lymphoma | Experimental | Rituximab (Standard of Care) will be administered for up to 6 cycles (28-day cycles).
Cycle 1: Days 1, 8, 15, and 22. Cycle 2-6: Day 1, every 28 days.
Rituximab: Intravenous rituximab formulations (IV rituximab or IV rituximab biosimilars will be administered by IV infusion at a dose of 375 mg/m2 per local institutional guidelines) or subcutaneous rituximab formulations (RITUXAN HYCELA) 1,400 mg/23,400 Units (1,400 mg rituximab and 23,400 Units hyaluronidase human) subcutaneously at a fixed dose per local institutional guidelines.
Zanubrutinib 320 mg will be administered orally once daily starting on day 1 of cycle 1.
Zanubrutinib will be continued once daily for up to 24 cycles or until disease progression or unacceptable toxicity occurs. Receives: Drug: Zanubrutinib; Drug: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate: Cohort A
Overall response rate will be determined using a 5 point scale per the Lugano criteria.
Measured: Up to 6 Months
Overall Response Rate: Cohort B
Overall response rate will be determined using a 5 point scale per the Lugano criteria.
Measured: Up to 6 Months
Secondary outcomes (2)
Efficacy of Zanubrutinib and Rituximab
Time to event endpoints (Progression free survival, Overall survival, duration of response, time to next anti-lymphoma therapy) will be summarized by Kaplan-Meier method for each cohort.
Measured: Up to 24 months
Safety and tolerability of combination Zanubrutinib and Rituximab
Safety and tolerability of the combination use of zanubrutinib and rituximab will be summarized descriptively by frequencies and percentages. Statistics will be given on type, severity, frequency, and attribution of adverse events.
Measured: Up to 24 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Apr 2024
- Study start19 Apr 2024
- Primary completionMar 2029 (estimated)
- Study completionMar 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Follicular LymphomaStudies of the same condition, open and under way.
- More trials run by H. Lee Moffitt Cancer Center and Research InstituteThe 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 43 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- BeOne Medicines
- Responsible party
- Sponsor
- Investigators
- Sameh Gaballa, MD, Principal investigator, Moffitt Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06350318
- Sponsor's protocol ID
- MCC-22005
- Status last verified
- Sep 2026
- First submitted
- 1 Apr 2024
- Last updated
- 28 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Open-Label, Multicenter Study of Rituximab and Zanubrutinib in Patients With Indolent B-cell Lymphomas
- ClinicalTrials.gov ID
- NCT06350318
- Acronym / sponsor ID
- MCC-22005
- Conditions
- Follicular Lymphoma, Marginal Zone Lymphoma, B-Cell Lymphoma
- Keywords
- B-Cell Lymphoma, Follicular Lymphoma, Marginal Zone Lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 43 participants (estimated)
- Lead sponsor
- H. Lee Moffitt Cancer Center and Research InstituteUniversity, hospital or other
- Collaborators
- BeOne Medicines
- Study start
- 19 Apr 2024 (actual)
- Primary completion
- Mar 2029 (estimated)
- Study completion
- Mar 2029 (estimated)
- First posted
- 5 Apr 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of the study is to establish the safety and efficacy of zanubrutinib in combination with rituximab for people with untreated B-cell lymphomas (marginal zone lymphoma and follicular lymphomas).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort A: Untreated Marginal Zone Lymphoma | Experimental | Drug: Zanubrutinib, Drug: RituximabRituximab (Standard of Care) will be administered for up to 6 cycles (28-day cycles). Cycle 1: Days 1, 8, 15, and 22. Cycle 2-6: Day 1, every 28 days. Rituximab: Intravenous rituximab formulations (IV rituximab or IV rituximab biosimilars will be administered by IV infusion at a dose of 375 mg/m2 per local institutional guidelines) or subcutaneous rituximab formulations (RITUXAN HYCELA) 1,400 mg/23,400 Units (1,400 mg rituximab and 23,400 Units hyaluronidase human) subcutaneously at a fixed dose per local institutional guidelines. Zanubrutinib 320 mg will be administered orally once daily starting on day 1 of cycle 1. Zanubrutinib will be continued once daily for up to 24 cycles or until disease progression or unacceptable toxicity occurs. |
| Cohort B: Untreated Follicular Lymphoma | Experimental | Drug: Zanubrutinib, Drug: RituximabRituximab (Standard of Care) will be administered for up to 6 cycles (28-day cycles). Cycle 1: Days 1, 8, 15, and 22. Cycle 2-6: Day 1, every 28 days. Rituximab: Intravenous rituximab formulations (IV rituximab or IV rituximab biosimilars will be administered by IV infusion at a dose of 375 mg/m2 per local institutional guidelines) or subcutaneous rituximab formulations (RITUXAN HYCELA) 1,400 mg/23,400 Units (1,400 mg rituximab and 23,400 Units hyaluronidase human) subcutaneously at a fixed dose per local institutional guidelines. Zanubrutinib 320 mg will be administered orally once daily starting on day 1 of cycle 1. Zanubrutinib will be continued once daily for up to 24 cycles or until disease progression or unacceptable toxicity occurs. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- Cohort A: Previously untreated MZL. Prior therapy with H. Pylori antibiotic therapy or hepatitis C antiviral therapy are allowed on Cohort A.
- Cohort B: Previously untreated FL
- Pathological confirmation of lymphoma: availability of archival tissue confirming diagnosis of MZL (cohort A) or FL (cohort B). Availability of formalin-fixed, paraffin-embedded (FFPE) archival tumor specimens from within past 18 months from screening and pathological diagnosis confirmed by a pathologist at the participating site or willingness of the participant to undergo a fresh tumor biopsy if adequate archival tissue not available is required. This includes:
- MZL (Cohort A):
- FL (Cohort B):
Key exclusion criteria (22 listed)
- Prior therapy for lymphoma including chemotherapy or immunotherapy. Participant may have received corticosteroids but should be off them 5 days prior to study entry.
- Prior exposure to a BTK inhibitor.
- Known prior significant hypersensitivity to rituximab (not including infusion reactions).
- Prior history of malignancies unless the patient has been disease free for ≥ 2 years. Exceptions include basal cell carcinoma or squamous cell carcinoma of the skin; carcinoma in situ of cervix; carcinoma in situ of breast, localized prostate cancer, or superficial bladder cancer that has undergone curative therapy.
- Participants with evidence of large B cell transformation or other aggressive histology (such as large cells seen on biopsy or high PET avidity in a single node seen on PET scan) are not eligible.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ZanubrutinibAlso: BrukinsaZanubrutinib is an anti-cancer medication administered orally. | Drug | Cohort A: Untreated Marginal Zone Lymphoma, Cohort B: Untreated Follicular Lymphoma |
| RituximabAlso: RituxinRituximab is a biologic medication administered intravenously or subcutaneously. | Drug | Cohort A: Untreated Marginal Zone Lymphoma, Cohort B: Untreated Follicular Lymphoma |
Primary outcome
Overall Response Rate: Cohort A
Time frame: Up to 6 Months
Overall response rate will be determined using a 5 point scale per the Lugano criteria.
Overall Response Rate: Cohort B
Time frame: Up to 6 Months
Overall response rate will be determined using a 5 point scale per the Lugano criteria.
2 secondary outcomes
Efficacy of Zanubrutinib and Rituximab
Time frame: Up to 24 months
Safety and tolerability of combination Zanubrutinib and Rituximab
Time frame: Up to 24 Months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2026.
Related trials for Follicular Lymphoma
RecruitingPhase 1/2
A Platform Trial Evaluating New Drugs or Combination in R/R Peripheral T-cell Lymphomas
Peripheral T Cells Lymphoma (PTCL), Follicular Helper T-Cell Lymphoma
Active, not recruiting
EXHIT ENTRE Implementation Trial of High Intensity Versus Low Intensity Strategy
Substance Use Disorders, Opioid Use Disorder, Severe
RecruitingPhase 1/2
Dose Escalation and Dose Expansion Study of MDX2003 in Patients With Different Types of Lymphoma
Lymphoma, Waldenström Macroglobulinemia (WM)
Active, not recruitingPhase 1
A Rollover Study of CC-122
Non-Hodgkin Lymphoma
Recruiting
STEpwise Research Program to Promote INGeniouS ONline Supportive Solutions in the Relief of Cancer-related Fatigue
Cancer Diagnosis, Moderate or Severe Score of Cancer-related Fatigue (CRF)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Sameh Gaballa, MD principal investigator
Moffitt Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Zanubrutinib and Rituximab in people with Follicular Lymphoma and Marginal Zone Lymphoma, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 28 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Richard Corona (813-745-3465, Richard.Corona@moffitt.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Response Rate: Cohort A (time frame: Up to 6 Months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Sep 2026.