Efficacy of Carfilzomib in Combination With Ibrutinib in Waldenström's Macroglobulinemia
Status:
Recruiting
Trial end date:
2028-02-01
Target enrollment:
Participant gender:
Summary
In Waldenström macroglobulinemia (WM) chemotherapy induces only low CR/VGPR (Complete
Remission/ Very Good Partial Response) rates and responses of short duration compared to
other indolent lymphomas. Thus, innovative approaches are needed which combine excellent
activity and tolerability in WM. Chemotherapy-free approaches are highly attractive for this
patient group. Based on its high activity in WM and its low toxicity, Ibrutinib was approved
for the treatment of WM by the European Medicines Agency (EMA). However, also Ibrutinib fails
to induce CRs and the VGPR rate is 16% in relapsed patients. In addition, activity of
Ibrutinib depends on the genotype: compared to MYD88mut/CXCR4WT patients Ibrutinib single
agent therapy induces substantially lower response rates in patients with the
MYD88mut/CXCR4mut or the MYD88WT/CXCR4WT genotype (major response (at least PR) in 91.7 %
compared to 61.9 and 0 %, respectively). Phase II data have indicated that the proteasome
inhibitor Carfilzomib is able to overcome the inferior prognosis of Ibrutinib in
MYD88mut/CXCR4mut and MYD88WT/CXCR4WT patients, as response rates were high for all genotypes
in a phase II study combining Carfilzomib with Rituximab and Dexamethasone. Based on this the
investigators hypothesize that addition of Carfilzomib to Ibrutinib will increase the VGPR/CR
rate compared to Ibrutinib alone in patients with WM, in particular in patients carrying the
CXCR4 mutation. In addition, the investigators hypothesize, that the combination Carfilzomib
and Ibrutinib will be also highly active in MYD88 wildtype patients and that this combination
will be at least as efficient in treatment naïve patients as in relapsed/refractory patients.
Phase:
Phase 3
Details
Lead Sponsor:
Christian Buske
Collaborators:
Amgen Institute of Epidemiology and Medical Biometry, University of Ulm Janssen, LP ZKS Ulm (Zentrum für Klinische Studien Ulm)