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

NCT06471738 | Recruiting Phase 2 DMC

• 1 other identifier: CHN-PLAGH-BT-086
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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) .

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

Outcome Measures

Primary Outcomes (1)

• CR rate

  Determined by PET/CT based on Cheson, Lugano classification 2014 as assessed by the investigator. The number and percentage of subjects with a CR will be tabulated.

  Within 6 months of therapy completion

Secondary Outcomes (4)

• 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

Study Arms (1)

Treatment (zanubrutinib, venetoclax, rituximab)

EXPERIMENTAL

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).

Drug: Zanubrutinib; Biological: Rituximab; Drug: Venetoclax

Interventions

Zanubrutinib DRUG

BTK inhibitor

Treatment (zanubrutinib, venetoclax, rituximab)

Rituximab BIOLOGICAL

Monoclonal antibody to CD20

Treatment (zanubrutinib, venetoclax, rituximab)

Venetoclax DRUG

BCL-2 inhibitor

Treatment (zanubrutinib, venetoclax, rituximab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Chinese PLA General Hospital: lead

Study Sites (1)

Biotherapeutic Department and Hematology Department of Chinese PLA General Hospital

Beijing, 100853, China

RECRUITING

MeSH Terms

Conditions

Lymphoma, Follicular

Interventions

zanubrutinib; Rituximab; venetoclax

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

YANG LIU, MD

CONTACT

010-66937463; liuyang301blood@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief physician.

Study Record Dates

• First Submitted: June 18, 2024
• First Posted: June 24, 2024
• Study Start: July 10, 2024
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): June 1, 2027
• Last Updated: July 18, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)