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

NCT ID: NCT06471738

Last Updated: 2024-07-18

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-07-10
• Study Completion Date: 2027-06-01

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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (zanubrutinib, venetoclax, rituximab)

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).

Group Type: EXPERIMENTAL

Zanubrutinib

Intervention Type: DRUG

BTK inhibitor

Rituximab

Intervention Type: BIOLOGICAL

Monoclonal antibody to CD20

Venetoclax

Intervention Type: DRUG

BCL-2 inhibitor

Interventions

Zanubrutinib

BTK inhibitor

Intervention Type: DRUG

Rituximab

Monoclonal antibody to CD20

Intervention Type: BIOLOGICAL

Venetoclax

BCL-2 inhibitor

Intervention Type: DRUG

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

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chinese PLA General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Han weidong

Chief physician.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Biotherapeutic Department and Hematology Department of Chinese PLA General Hospital

Beijing, , China

Site Status: RECRUITING

Countries

China

Central Contacts

YANG LIU, MD

Role: CONTACT

liuyang301blood@163.com

010-66937463

Facility Contacts

Weidong Han

Role: primary

hanwdrsw@sina.com

86-10-13651392893

Other Identifiers

CHN-PLAGH-BT-086

Identifier Type: -

Identifier Source: org_study_id