Study Evaluating the Efficacy and Tolerance of a Zanubrutinib and BGB-11417 Combination in Patients Previously Treated for Waldenström Macroglobulinemia
NCT Number: NCT06547866
Acronym: WAZABI
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Waldenstrom Macroglobulinemia
Interventions: DRUG: zanubrutinib + BGB-11417
Sponsor: French Innovative Leukemia Organisation
Collaborators: BeiGene
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 102
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-10-01
Completion Date: 2031-03-31
Locations: AMIENS - CH Amiens Picardie Site Sud, Amiens, 80054, France|Angers Chu, Angers, 49933, France|ANNECY - CH Annecy Genevois, Annecy, 74374, France|ARGENTEUIL - Centre hospitalier Victor Dupouy, Argenteuil, France|BAYONNE - CH de la Côte Basque - Hématologie, Bayonne, 64109, France|BESANCON - Hôpital Jean Minjoz, Besançon, 25000, France|Bordeaux-Institut Bergonié, Bordeaux, 33076, France|CAEN - CHU Caen - IHBN, Caen, 14033, France|Clermont-Ferrand - Chu Estaing, Clermont-Ferrand, 63000, France|CRETEIL - CHU Henri Mondor, Créteil, 94000, France|DIJON - Hôpital François Mitterrand, Dijon, 21000, France|Grenoble - CHUGA - Hématologie Clinique, Grenoble, 38043, France|La Roche Sur Yon - Chd Vendee, La Roche-sur-Yon, 85925, France|Le Mans CH, Le Mans, France|LILLE GHICL - Hôpital Saint Vincent de Paul, Lille, 59000, France|LILLE CHU - Hôpital Claude Huriez, Lille, 59037, France|LYON-Centre Léon Bérard, Lyon, 69008, France|MARSEILLE - Institut Paoli-Calmettes, Marseille, 13000, France|MONTPELLIER - Hôpital Saint-Eloi - Hématologie Clinique, Montpellier, 34295, France|Mulhouse - Ghrmsa, Mulhouse, 68100, France|NANTES - Hôpital Hôtel Dieu - Hématologie Clinique, Nantes, 44093, France|ORLEANS - CHR - Hématologie, Orléans, 44100, France|APHP - Hôpital Pitié Salpêtrière - Hématologie, Paris, 75651, France|PERPIGNAN - CH St Jean - Hématologie Clinique, Perpignan, 66000, France|Bordeaux Pessac, Pessac, 33604, France|LYON HCL - CH Lyon Sud, Pierre-Bénite, 69036, France|POITIERS - Hématologie et Thérapie Cellulaire, Poitiers, 86021, France|Reims Chu, Reims, 51092, France|RENNES - CHU Pontchaillou - Hématologie Clinique, Rennes, 35033, France|ROUEN - Centre Henri Becquerel - Service Hématologie Clinique, Rouen, 76038, France|Strasbourg - Icans, Strasbourg, 67033, France|Toulouse - IUCT Oncopole - Service d'Hématologie, Toulouse, 31059, France|TOURS - Hôpital Bretonneau, Tours, 37000, France|NANCY - CHU Brabois, Vandœuvre-lès-Nancy, 54500, France|Vannes - Chba, Vannes, France|VERSAILLES - Hôpital André Mignot, Versailles, France|Villejuif Igr, Villejuif, France

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

Primary Outcome Measures: Primary endpoint, Number of subjects achieving a CR or VGPR at any time during the course of treatment, twenty 28-days cycles
Secondary Outcome Measures: Overall response rate (ORR), Number of subjects achieving a best response (CR, VGPR, PR or minor response), at any time during the course of study treatment (twenty 28-days cycles)|Major response rate (MRR), Number of subjects achieving a best response (CR, VGPR or PR), at any time during the course of study treatment (twenty 28-days cycles)|Time to response (TTR), time to achieve of at least a minor response, From start to end of treatment (twenty 28-days cycles)|Progression free survival (PFS), time to disease progression or death from any cause, From start of treatment to end fo Fup (twenty 28-days cycles + 3 years Fup)