Efficacy of Venetoclax in Combination With Rituximab in Waldenström's Macroglobulinemia
Status:
Not yet recruiting
Trial end date:
2029-12-01
Target enrollment:
Participant gender:
Summary
In Waldenström's macroglobulinemia (WM) chemotherapy induces only low CR/VGPR rates and
response duration is limited. In addition, WM patients are often elderly, partly not
tolerating chemotherapy related toxicities. 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 and favorable toxicity profile
in indolent B-NHL such as CLL, Venetoclax was approved for the treatment of this diseases by
the FDA and the European Medicines Agency (EMA). First data in relapsed/refractory WM have
documented high activity and low toxicity of Venetoclax also in WM, including patients with
prior Ibrutinib treatment or patients carrying CXCR4 mutations. Ibrutinib itself has high
activity and a relatively low toxicity profile in WM, but has also major disadvantages: the
main disadvantage is the need to apply this drug continuously. Furthermore, Ibrutinib
efficacy depends largely on the genotype with a substantial drop in major responses and PFS
in the presence of CXCR4 mutations and non-mutated MYD88. In particular the need of
continuous treatment for Ibrutinib has prevented that Ibrutinib has become the standard of
care outcompeting conventional Rituximab/chemotherapy. This is reflected in current
guidelines such as the NCCN and the ESMO guidelines, which still see immunochemotherapy as a
backbone of treatment, largely because of the advantage of a timely fixed application. Data
in CLL in the relapsed as well as in the first line setting have convincingly shown that in
contrast to Ibrutinib Venetoclax is highly efficient also when used in a timely defined
application scheme over 12 months in combination with the anti-CD20 antibody Rituximab. Data
documented deep responses including molecular responses and a highly significant advantage
over immunochemotherapy in large international Phase III trials, changing the standard of
care in this disease.
Based on this the hypothesis is that timely fixed application of the combination of
Venetoclax and Rituximab induces significantly superior treatment outcomes compared to
chemotherapy and Rituximab (DRC) in patients with treatment naïve WM, regardless of the
genotype. A confirmation of this assumption in the proposed trial will change the standard of
care in WM.
Phase:
Phase 2
Details
Lead Sponsor:
University of Ulm
Collaborators:
AbbVie Institute for Medical Informatics, Biometry and Epidemiology, University of Munich Pfizer Zentrum für Klinische Studien Ulm