Safety and Efficacy of Zanubrutinib in Combination With Rituximab and Venetoclax in Previously Untreated Follicular Lymphoma: An Open Label, Phase 2 Study
Combination of Zanubrutinib, Rituximab and Venetoclax in Patients With Previously Untreated Follicular Lymphoma
Sponsors
Source
Chinese PLA General Hospital
Oversight Info
Has Dmc
Yes
Is Fda Regulated Drug
No
Is Fda Regulated Device
No
Brief Summary
This is a single center, open label, single arm phase II clinical trial. The objective of
this study is to assess the feasibility and efficacy of zanubrutinib combined with
venetoclax and Rituximab in patients with previously untreated follicular lymphoma (FL) .
Detailed Description
Follicular lymphoma (FL)is the most common inert non Hodgkin's lymphoma (iNHL). Their
natural courses are slow but highly variable. The standard first-line treatment of
advanced FL is based on rituximab. Whether combined with chemotherapy or not, it can
induce lasting remission, but it is usually incurable. Although the first-line
immunochemotherapy regimen has high efficacy, it also has high toxicity. Cytotoxic
chemotherapy is related to many side effects, including bone marrow suppression and
immunosuppression, gastrointestinal and cardiac toxicity, neurotoxicity and the
occurrence of secondary tumors. About 20% of FL patients relapse within 2 years after
first-line chemotherapy. The overall prognosis of these patients is poor. This clinical
trial aims to evaluate the feasibility and efficacy of free-chemotherapy regimen
(zanubrutinib combined with venetoclax and Rituximab) in patients with previously
untreated follicular lymphoma.
Overall Status
Recruiting
Start Date
2024-07-10
Completion Date
2027-06-01
Primary Completion Date
2026-12-30
Phase
Phase 2
Study Type
Interventional
Primary Outcome
Measure |
Time Frame |
|
CR rate |
Within 6 months of therapy completion |
Secondary Outcome
Measure |
Time Frame |
|
Overall response rate (ORR) |
Within 6 months of therapy completion |
|
Progression-free survival |
up to two years |
|
Overall survival |
up to two years |
|
Incidence of Treatment-Emergent Adverse Events |
Up to 90 days after the last dose of study drugs |
Enrollment
30
Conditions
Intervention
Intervention Type
Drug
Intervention Name
Description
BTK inhibitor
Arm Group Label
Treatment (zanubrutinib, venetoclax, rituximab)
Intervention Type
Biological
Intervention Name
Description
Monoclonal antibody to CD20
Arm Group Label
Treatment (zanubrutinib, venetoclax, rituximab)
Intervention Type
Drug
Intervention Name
Description
BCL-2 inhibitor
Arm Group Label
Treatment (zanubrutinib, venetoclax, rituximab)
Eligibility
Criteria
Inclusion Criteria:
- A diagnosis of follicular lymphoma (grades 1, 2, or 3a), untreated.
- Stage II, III, or IV disease.
- Able and willing to provide written informed consent and to comply with the study
protocol.
- at least one measurable disease.
- Must be in need of therapy as evidenced by at least one of the following criteria:
- Presence of at least one B symptom: Fever (> 38 Celsius [C]) not due to
infectious etiology, or Night sweats, or Weight loss > 10% in the past 6
months;
- Fatigue due to lymphoma;
- Splenomegaly (> 13 cm);
- Compression syndrome (ureteral, orbital, gastrointestinal);
- Any of the following cytopenias, due to lymphoma: Hemoglobin ≤ 10 g/dL, or
Platelets ≤ 100 x 10^9/L, or Absolute neutrophil count (ANC) < 1.5 x 10^9/L;
- Pleural or peritoneal effusion;
- Lactate dehydrogenase (LDH) > upper limit of normal (ULN) or beta (B)2
microglobulin > ULN;
- Other lymphoma-mediated symptoms as determined by the treating physician.
- ECOG ≤ 2
- ANC > 1.0 x 10^9/L (for patients without bone marrow involvement by lymphoma)
- Platelet count > 50 x 10^9/L (for patients without bone marrow involvement by
lymphoma)
- Prothrombin time (PT)/international normal ratio (INR) < 1.5 x (upper limit of
normal) ULN and partial thromboplastin time (PTT) (activated partial thromboplastin
time [aPTT]) < 1.5 x ULN (unless abnormalities are unrelated to coagulopathy or
bleeding disorder). When treated with warfarin or other vitamin K antagonists, then
INR ≤ 3.0)
- Serum aspartate transaminase (AST) and alanine transaminase (ALT) < 3 x ULN
- Creatinine clearance > 30 ml/min calculated by modified Cockcroft-Gault formula
- Bilirubin < 1.5 x ULN unless bilirubin is due to Gilbert's syndrome, documented
liver involvement with lymphoma, or of non-hepatic origin, in which case bilirubin
should not exceed 3 g/dL
- Women of childbearing potential must have a negative serum (beta-human chorionic
gonadotropin [B-hCG]) pregnancy test at screening. Women who are pregnant or
breastfeeding are ineligible for this study
Exclusion Criteria:
- Known active central nervous system lymphoma or leptomeningeal disease
- Follicular lymphoma with evidence of diffuse large B-cell transformation
- Grade 3b follicular lymphoma
- Any prior history of other malignancy besides follicular lymphoma
- History of severe allergic or anaphylactic reactions to monoclonal antibody therapy
- Patients who have undergone major surgery within 14 days
- The researchers believe that it is not advisable for the participant to take part in
this trial.
Gender
All
Minimum Age
18 Years
Maximum Age
N/A
Healthy Volunteers
No
Overall Contact
Last Name
YANG LIU, MD
Phone
010-66937463
liuyang301blood@163.com
Location
Facility |
Status |
Contact |
|
Biotherapeutic Department and Hematology Department of Chinese PLA General Hospital Beijing 100853 China |
Recruiting |
Last Name: Weidong Han Phone: 86-10-13651392893 Email: hanwdrsw@sina.com |
Location Countries
Country
China
Verification Date
2026-07-01
Lastchanged Date
N/A
Firstreceived Date
N/A
Responsible Party
Responsible Party Type
Principal Investigator
Investigator Affiliation
Chinese PLA General Hospital
Investigator Full Name
Han weidong
Investigator Title
Chief physician.
Has Expanded Access
No
Condition Browse
Number Of Arms
1
Intervention Browse
Mesh Term
zanubrutinib
Rituximab
venetoclax
Arm Group
Arm Group Label
Treatment (zanubrutinib, venetoclax, rituximab)
Arm Group Type
Experimental
Description
stage I (cycles 1-3, every 4 weeks): zanubrutinib PO 160mg, BID; rituximab IV on day 1.
stage II (cycles 4-9, every 4 weeks): if complete response : zanubrutinib PO 160mg, BID;
rituximab IV on day 1.
if no complete response : zanubrutinib PO160mg, BID; rituximab IV on day 1 and Venetoclax
PO (100mg D1, 200mg D2, and 400mg D3 of cycle 4; 400mg QD).
Firstreceived Results Date
N/A
Patient Data
Sharing Ipd
No
Firstreceived Results Disposition Date
N/A
Study Design Info
Allocation
N/A
Intervention Model
Single Group Assignment
Primary Purpose
Treatment
Masking
None (Open Label)
Study First Submitted
June 18, 2024
Study First Submitted Qc
June 18, 2024
Study First Posted
June 24, 2024
Last Update Submitted
July 16, 2026
Last Update Submitted Qc
July 16, 2026
Last Update Posted
July 20, 2026
ClinicalTrials.gov processed this data on October 07, 2026
Conditions
Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov,
conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions
Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied.
Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase
Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions
that study is seeking to answer:
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.