Study Evaluating the Efficacy and Tolerance of a Zanubrutinib and BGB-11417 Combination in Patients Previously Treated for Waldenström Macroglobulinemia

NCT06547866 | Not Yet Recruiting Phase 2

• 1 other identifier: FILOWM4-WAZABI
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 37

Brief Summary

This is a French multicenter open label non-randomized Phase II trial evaluating the efficacy and tolerance of a combination of oral zanubrutinib and BGB-11417 in subjects aged 18 years and older with previously treated Waldenström macroglobulinemia (WM) who require therapy according to the consensus panel criteria from the Second International Workshop on Waldenström's macroglobulinemia. population : Patients with previously treated Waldenstrom macroglobulinemia The investigational medicinal products (IMP) are Zanubrutinib (BGB- 3111) and BGB-11417.Treatment will be administered for a total of twenty 28 day cycles:

• Cycle 1 with zanubrutinib only
• Cycle 2 with zanubrutinib plus BGB-11417 ramp-up
• cycle 2, day 1 : 10mg
• cycle 2, day 2 : 20 mg
• cycle 2, day 3 : 40mg
• cycle 2, day 4-7 : 80md daily
• cycle 2, day 8 and beyond : 160 mg daily
• Cycles 3-20 with zanubrutinib plus BGB-11417 full dose

Conditions

Waldenstrom Macroglobulinemia

Outcome Measures

Primary Outcomes (1)

• Primary endpoint

  Number of subjects achieving a CR or VGPR at any time during the course of treatment

  twenty 28-days cycles

Secondary Outcomes (4)

• Overall response rate (ORR)

  at any time during the course of study treatment (twenty 28-days cycles)

• Major response rate (MRR)

  at any time during the course of study treatment (twenty 28-days cycles)

• Time to response (TTR)

  From start to end of treatment (twenty 28-days cycles)

• Progression free survival (PFS)

  From start of treatment to end fo Fup (twenty 28-days cycles + 3 years Fup)

Study Arms (1)

Zanubrutinb + BGB-11417

EXPERIMENTAL

cf intervention

Drug: zanubrutinib + BGB-11417

Interventions

zanubrutinib + BGB-11417 DRUG

The investigational medicinal products (IMP) are Zanubrutinib (BGB- 3111) and BGB-11417.Treatment will be administered for a total of twenty 28 day cycles: Cycle 1 with zanubrutinib only Cycle 2 with zanubrutinib plus BGB-11417 ramp-up cycle 2, day 1 : 10mg cycle 2, day 2 : 20 mg cycle 2, day 3 : 40mg cycle 2, day 4-7 : 80md daily cycle 2, day 8 and beyond : 160 mg daily Cycles 3-20 with zanubrutinib plus BGB-11417 full dose

Zanubrutinb + BGB-11417

Eligibility Criteria

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

You may qualify if:

• Be ≥ 18-year-old.
• Provide written informed consent.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 3.
• Have adequate renal function defined as creatinine clearance ≥ 50 mL/min as determined by the Cockroft-Gault equation.
• Have adequate hepatic function defined as:
• total serum bilirubin ≤ 1.5 × ULN, unless bilirubin rise is due to Gilbert's syndrome or non-hepatic cause.
• alanine aminotransferase (ALAT) \< 2 × ULN
• aspartate aminotransferase (ASAT) \< 2 × ULN,
• Have adequate BM function defined as:
• absolute neutrophil count ≥ 1x109/L
• platelet count ≥ 75 x109/L
• For women of childbearing potential, a negative pregnancy test must be documented prior to enrollment.
• A woman is considered of childbearing potential, ie, fertile, following menarche and until becoming postmenopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy.
• A post-menopausal state is defined as no menses for 12 months without an alternative medical cause.
• Agree to use a highly effective form of contraception with sexual partners throughout study participation (for female and male patients who are fertile). Patients using hormonal contraceptives (eg, birth control pills or devices) must use a barrier method of contraception (eg, condoms) as well.

You may not qualify if:

• Have previously been treated with a BTK inhibitor.
• Have been previously treated with a bcl-2 antagonist.
• Have active central nervous system (CNS) disease as evidenced by cytology or pathology. In the absence of clinical signs of CNS disease, a lumbar puncture is not mandatory.
• Have significant or active cardiovascular disease:
• stage III to IV congestive heart failure (CHF) as determined by the New York Heart Association (NYHA) classification system for heart failure and/or with left ventricular ejection fraction \< 50%
• myocardial infarction within 6 months before study treatment.
• unstable angina within 6 months before study treatment.
• uncontrolled atrial arrhythmia.
• history of clinically significant ventricular arrhythmias (e.g sustained ventricular tachycardia, ventricular fibrillation, torsades de pointe).
• uncontrolled hypertension.
• history of stroke or intracranial hemorrhage within 180 days before the first dose of study drugs
• QTcF interval \> 450 ms on screening electrocardiogram (ECG) evaluation.
• Have a history of stroke or intracranial hemorrhage within 6 months before first dose of study drug, have a history of a severe bleeding disorder such as hemophilia A, hemophilia B, von Willebrand disease, or history of spontaneous bleeding requiring blood transfusion or other medical intervention:
• patients with constitutional hemophilia or von Willebrand's disease will be excluded.
• patients with acquired hemophilia will be excluded.

Sponsors & Collaborators

• French Innovative Leukemia Organisation: lead
• BeiGene: collaborator

Study Sites (37)

AMIENS - CH Amiens Picardie Site Sud

Amiens, 80054, France

Location

Angers Chu

Angers, 49933, France

Location

ANNECY - CH Annecy Genevois

Annecy, 74374, France

Location

ARGENTEUIL - Centre hospitalier Victor Dupouy

Argenteuil, France

Location

BAYONNE - CH de la Côte Basque - Hématologie

Bayonne, 64109, France

Location

BESANCON - Hôpital Jean Minjoz

Besançon, 25000, France

Location

Bordeaux-Institut Bergonié

Bordeaux, 33076, France

Location

CAEN - CHU Caen - IHBN

Caen, 14033, France

Location

Clermont-Ferrand - Chu Estaing

Clermont-Ferrand, 63000, France

Location

CRETEIL - CHU Henri Mondor

Créteil, 94000, France

Location

DIJON - Hôpital François Mitterrand

Dijon, 21000, France

Location

Grenoble - CHUGA - Hématologie Clinique

Grenoble, 38043, France

Location

La Roche Sur Yon - Chd Vendee

La Roche-sur-Yon, 85925, France

Location

Le Mans CH

Le Mans, France

Location

LILLE GHICL - Hôpital Saint Vincent de Paul

Lille, 59000, France

Location

LILLE CHU - Hôpital Claude Huriez

Lille, 59037, France

Location

LYON-Centre Léon Bérard

Lyon, 69008, France

Location

MARSEILLE - Institut Paoli-Calmettes

Marseille, 13000, France

Location

MONTPELLIER - Hôpital Saint-Eloi - Hématologie Clinique

Montpellier, 34295, France

Location

Mulhouse - Ghrmsa

Mulhouse, 68100, France

Location

NANTES - Hôpital Hôtel Dieu - Hématologie Clinique

Nantes, 44093, France

Location

ORLEANS - CHR - Hématologie

Orléans, 44100, France

Location

APHP - Hôpital Pitié Salpêtrière - Hématologie

Paris, 75651, France

Location

PERPIGNAN - CH St Jean - Hématologie Clinique

Perpignan, 66000, France

Location

Bordeaux Pessac

Pessac, 33604, France

Location

LYON HCL - CH Lyon Sud

Pierre-Bénite, 69036, France

Location

POITIERS - Hématologie et Thérapie Cellulaire

Poitiers, 86021, France

Location

Reims Chu

Reims, 51092, France

Location

RENNES - CHU Pontchaillou - Hématologie Clinique

Rennes, 35033, France

Location

ROUEN - Centre Henri Becquerel - Service Hématologie Clinique

Rouen, 76038, France

Location

Strasbourg - Icans

Strasbourg, 67033, France

Location

Toulouse - IUCT Oncopole - Service d'Hématologie

Toulouse, 31059, France

Location

TOURS - Hôpital Bretonneau

Tours, 37000, France

Location

NANCY - CHU Brabois

Vandœuvre-lès-Nancy, 54500, France

Location

Vannes - Chba

Vannes, France

Location

VERSAILLES - Hôpital André Mignot

Versailles, France

Location

Villejuif Igr

Villejuif, France

Location

MeSH Terms

Conditions

Waldenstrom Macroglobulinemia

Interventions

zanubrutinib

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Kamel Laribi, MD

  CH Le Mans

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Adeline Lhermitte

CONTACT

+33787888464; a.lhermitte@filo-leucemie.org

Valérie Rouillé

CONTACT

+33247473798; v.rouille@filo-leucemie.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2024
• First Posted: August 9, 2024
• Study Start: December 1, 2025
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2031
• Last Updated: November 26, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

FR (37)