Bendamustine, Rituximab and Acalabrutinib in Waldenstrom's Macroglobulinemia

Titre officiel

A Multi-Centre, Open-Label, Single-Arm Phase II Trial of Bendamustine, Rituximab and the Second Generation BTK Inhibitor Acalabrutinib in Previously Untreated Waldenstrom's Macroglobulinemia

Sommaire:

Il s’agit d’un essai clinique ouvert et multicentrique de phase II à groupe unique chez des patients non traités atteints de la macroglobulinémie de Waldenström. Les patients symptomatiques qui n’ont jamais été traités recevront de la bendamustine et du rituximab de référence pendant 6 cycles de 28 jours. La bendamustine sera administrée par voie intraveineuse à raison de 90 mg/m2 les jours 1 et 2 de chaque cycle. Le rituximab sera administré le jour 1 de chaque cycle (375 mg/m2 par voie intraveineuse pour le premier cycle et 1 400 mg par voie sous-cutanée OU 375 mg/m2 par voie intraveineuse pour les cycles suivants [selon les procédures de l’établissement]). En concomitance, les participants recevront 100 mg du produit expérimental, Acalabrutinib, par voie orale pendant 1 an (365 jours), à raison de 100 mg deux fois par jour.

Description de l'essai

Primary Outcome:

• Best combined complete response (CR) and very good partial response (VGPR)

Secondary Outcome:

• Overall objective response and partial response
• Documentation of minimal residual disease (MRD) rate
• Documentation of overall survival
• Documentation of progression free survival
• Toxicities graded according to the NCI Common Terminology Criteria for Adverse Events, version 5.0 (NCI CTCAE, v5.0)]

This is a multi-centre, open label, single-arm, phase II clinical trial in untreated patients with WM. Patients will require a biopsy to confirm the pathology and molecular testing for MYD88, CXCR4 and P53 mutations. A bone marrow aspiration and biopsy will be performed to document WM and MRD. Participants will be classified into clinical risk categories based on the International Prognostic Scoring (IPS) System for WM. Symptomatic, previously untreated patients will receive SOC bendamustine and rituximab for 6 28-day cycles. Bendamustine will be given intravenously at 90 mg/m2 on days 1 and 2 of each cycle. Rituximab will be given on day 1 of each cycle (375 mg/m2 intravenously for the first cycle and 1400 mg subcutaneously OR 375 mg/m2 intravenously for subsequent cycles (as per institutional procedures)). Concomitantly, participants will receive 100 mg of the investigational product, Acalabrutinib, orally for 1 year (365 days) at 100 mg BID. Patients will have pre-treatment computed tomography (CT) scans, and CT scans at 7, 12 and 18 months. Best objective response will be documented using the criteria from the Sixth International Workshop on Waldenstrom's Macroglobulinemia. Assessment of metabolic uptake by positron emission tomography (PET) scan is not considered appropriate for WM as WM usually do not take up fluorodeoxyglucose (FDG). Patients with WM will also have disease assessed using measurements of serum IgM, serum protein electrophoresis (SPE), immunofixation (IFA), and viscosity assessments measured serially. A bone marrow aspiration and biopsy will be done before treatment and at response assessment at cycle 6 and will be repeated if positive. Durability of response will also be assessed at 18 months. Participants will be followed by extended follow-up by telephone for up to 6 years to obtain data on the secondary endpoints.

Voir cet essai sur ClinicalTrials.gov