Non-invasive Diagnostics and Monitoring of MRD and Clonal Evolution in Waldenström's Macroglobulinemia and in IgM-MGUS

Active, not recruiting

• Conditions: Waldenstrom Macroglobulinemia
• Interventions: Other: MRD and clonal evolution

• Registration Number: NCT03521596
• Lead Sponsor: Fondazione Italiana Linfomi - ETS

Brief Summary

Multicenter retrospective and prospective observational study including patients with WM or IgM-MGUS evaluated at the time of diagnosis and during the disease course using highly sensitive techniques.

Detailed Description

Multicenter retrospective and prospective observational study including patients with WM or IgM-MGUS evaluated at the time of diagnosis and during the disease course using highly sensitive techniques such as flow cytometry, real time quantitative PCR (RT-qPCR), digital droplet PCR (dd-PCR) and NGS, in order to: evaluate the mutational status on genomic DNA or cell-free DNA and compare the results to assess the most reliable source for mutation studies; perform and compare molecular and flow cytometry analyses on bone marrow, peripheral blood (both analyses), plasma and urine samples (only molecular analysis) to assess the best source for diagnosis and MRD monitoring.

Study Timeline

• Study First Submitted: 2018-04-30
• Study First Submitted QC: 2018-04-30
• Study First Posted: 2018-05-11
• Study Start: 2018-08-28
• Primary Completion: 2020-10-06
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-20
• Last Update Posted: 2024-06-21
• Study Completion: 2025-10

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

• Diagnosis of IgM monoclonal gammopathy of undetermined significance (Ig-MGUS) or Waldenström's Macroglobulinemia (WM) according to criteria established at the second International Workshop on Waldenström's Macroglobulinemia [1]
• Age ≥ 18 years
• Previously untreated patients (only for the prospective cohort)
• Symptomatic or asymptomatic disease
• Subject understands and voluntarily signs an informed consent form approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB)

Exclusion Criteria

• Active HBV, HCV or HIV infection (antiHBc+ patients with undetectable HBV-DNA are eligible to the study)

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Patient enrolled	MRD and clonal evolution	Part of the patients will be retrospectively enrolled (learning sample) and part prospectively (validation sample)

Primary Outcome Measures

Name	Time	Method
Rate of mutation	22 months	To demonstrate that the rate of mutations of MYD88 (L265P) and/or CXCR4 (S338X) detected in peripheral blood and/or urine show a negligible difference with the rate of mutations detected in bone marrow samples (BM, gold standard)

Trial Locations

Locations (14)

SOS Ematologia Ospedale C. Massaia; 🇮🇹 Asti, Italy

Divisione di Ematologia Ospedale Niguarda; 🇮🇹 Milano, MI, Italy

A.O. Universitaria Di Parma; 🇮🇹 Parma, Italy

A.O. Città della Salute e della Scienza Ematologia Universitaria; 🇮🇹 Torino, Italy

Azienda Sanitaria Universitaria Integrata di Udine (A.S.U.I. Udine) - PO S. Maria della Misericordia; 🇮🇹 Udine, Italy

Policlinico A. Gemelli Università Cattolica del Sacro Cuore; 🇮🇹 Roma, Italy

AOU Università degli Studi della Campania Luigi Vanvitelli; 🇮🇹 Napoli, Italy

Ospedale degli Infermi di Rimini; 🇮🇹 Rimini, Italy

Ematologia - OSPEDALE DI CIRCOLO E FONDAZIONE MACCHI; 🇮🇹 Varese, Italy

IRCCS Istituto Tumori Giovanni Paolo II - UOC Ematologia; 🇮🇹 Bari, Italy

I.R.C.C.S. Istituto Oncologico Veneto - Oncologia 1; 🇮🇹 Padova, Italy

Ematologia Policlinico San Matteo; 🇮🇹 Pavia, Italy

AO Arcispedale Santa Maria Nuova - IRCCS; 🇮🇹 Reggio Emilia, Italy

UOC Ematologia, AOU Senese; 🇮🇹 Siena, Italy