Clinical trial NCT03521596: Non-invasive Diagnostics and Monitoring of MRD and Clonal Evolution in Waldenström's Macroglobulinemia and in IgM-MGUS
Official title: Non-invasive Diagnostics and Monitoring of Minimal Residual Disease and Clonal Evolution in Waldenström's Macroglobulinemia and in IgM Monoclonal Gammopathy of Undetermined Significance
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Waldenstrom Macroglobulinemia
Keywords: IgM monoclonal gammopathy
Waldenström's Macroglobulinemia
Minimal residual disease
Clonal evolution
Lead sponsor: Fondazione Italiana Linfomi - ETS
Sponsor class: OTHER
First posted: 2018-05-11
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: PROBABILITY_SAMPLE
Study population: The study population will include either IgM-MGUS, asymptomatic WM or symptomatic WM patients requiring treatment. Patients in need of therapy will be treated according to recently published guidelines \[49\]. Patients treated with new agents, including the BTK inhibitor Ibrutinib, will be included. Patient enrolled retrospectively will constitute the learning cohort of the study, while those enrolled prospectively will constitute the validation cohort).

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Rate of mutation
timeFrame: 22 months
Secondary outcomes:
Other outcomes:
Locations:
city: Milano
country: Italy
facility: Divisione di Ematologia Ospedale Niguarda
state: MI
city: Asti
country: Italy
facility: SOS Ematologia Ospedale C. Massaia
city: Bari
country: Italy
facility: IRCCS Istituto Tumori Giovanni Paolo II - UOC Ematologia
city: Napoli
country: Italy
facility: AOU Università degli Studi della Campania Luigi Vanvitelli
city: Padova
country: Italy
facility: I.R.C.C.S. Istituto Oncologico Veneto - Oncologia 1
city: Parma
country: Italy
facility: A.O. Universitaria Di Parma
city: Pavia
country: Italy
facility: Ematologia Policlinico San Matteo
city: Reggio Emilia
country: Italy
facility: AO Arcispedale Santa Maria Nuova - IRCCS
city: Rimini
country: Italy
facility: Ospedale degli Infermi di Rimini
city: Roma
country: Italy
facility: Policlinico A. Gemelli Università Cattolica del Sacro Cuore
city: Siena
country: Italy
facility: UOC Ematologia, AOU Senese
city: Torino
country: Italy
facility: A.O. Città della Salute e della Scienza Ematologia Universitaria
city: Udine
country: Italy
facility: Azienda Sanitaria Universitaria Integrata di Udine (A.S.U.I. Udine) - PO S. Maria della Misericordia
city: Varese
country: Italy
facility: Ematologia - OSPEDALE DI CIRCOLO E FONDAZIONE MACCHI
Study officials:
affiliation: Pavia - IRCCS Policlinico S. Matteo di Pavia - Div. di Ematologia
name: Marzia Varettoni
role: PRINCIPAL_INVESTIGATOR
References: