Combination of Zanubrutinib, Rituximab and Venetoclax in Patients With Previously Untreated Follicular Lymphoma

Trial Title: Combination of Zanubrutinib, Rituximab and Venetoclax in Patients With Previously Untreated Follicular Lymphoma

NCT ID: NCT06471738

Condition: Ann Arbor Stage II Follicular Lymphoma
Grade 1 Follicular Lymphoma
Ann Arbor Stage III Follicular Lymphoma
Ann Arbor Stage IV Follicular Lymphoma
Grade 2 Follicular Lymphoma
Grade 3a Follicular Lymphoma

Conditions: Official terms:
Lymphoma
Lymphoma, Follicular
Rituximab
Venetoclax
Zanubrutinib

Study type: Interventional

Study phase: Phase 2

Overall status: Recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Zanubrutinib
Description: BTK inhibitor
Arm group label: Treatment (zanubrutinib, venetoclax, rituximab)

Intervention type: Biological
Intervention name: Rituximab
Description: Monoclonal antibody to CD20
Arm group label: Treatment (zanubrutinib, venetoclax, rituximab)

Intervention type: Drug
Intervention name: Venetoclax
Description: BCL-2 inhibitor
Arm group label: Treatment (zanubrutinib, venetoclax, rituximab)

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.

Criteria for 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 - Night sweats - 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 - Platelets ≤ 100 x 10^9/L - 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 Exclusion Criteria: - ECOG≤ 2 - Absolute neutrophil count (ANC) > 1.0 x 10^9/L - Platelet count > 50 x 10^9/L - 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 upper limit of normal (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

Locations:

Facility:
Name: Biotherapeutic Department and Hematology Department of Chinese PLA General Hospital

Address:
City: Beijing
Zip: 100853
Country: China

Status: Recruiting

Contact:
Last name: Weidong Han

Phone: 86-10-13651392893
Email: hanwdrsw@sina.com

Start date: July 10, 2024

Completion date: June 1, 2027

Lead sponsor:
Agency: Chinese PLA General Hospital
Agency class: Other

Source: Chinese PLA General Hospital

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06471738