Clinical trial NCT04352556: COVID19-hematological Malignancies: the Italian Hematology Alliance
Official title: SARS-CoV-2 Infection in Patients With Hematological Malignancies: the Italian Hematology Alliance
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: SARS-CoV-2 Infection
Hematological Malignancies
Keywords: Hematological Malignancies
Covid-19
SARS-CoV-2
Italian Hematology Alliance
Leukemia
Lymphoma
Multiple Myeloma
Lead sponsor: Ospedale di Circolo - Fondazione Macchi
Sponsor class: OTHER
First posted: 2020-04-20
Enrollment: 250
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population will must be older than 18 years of age with Hematological malignancies and SARS-CoV-2 infection.

Brief summary: This is a retrospective/prospective, cohort, non-interventional observational study. This means that all patients with documented COVID and HM diagnosed between February 2020 and study initiation will compose the retrospective part, while those diagnosed after study approval will enter prospective part.

The total duration of the study will be 12 months.

The study population will must be older than 18 years of age with HM and SARS-CoV-2 infection. All patients with documented SARS-CoV-2 infection (COVID) and history or active hematological malignancies, who refer to any Hematological Unit will be included.

Detailed description: This is a retrospective/prospective, cohort, non-interventional observational study. An informed consensus for the participation is available. In this section we provide informations on sample size and statistical analysis.

In Italy, the projected estimate of complete HM prevalence at Jan 1, 2020 has been established as 48,254 cases for Hodgkin lymphoma, 110.715 cases for non Hodgkin Lymphomas, 67,301 for leukemias, and 25,066 for multiple myeloma (Guzzinati et al, BMC Cancer 2018). The Italian Dipartimento della Protezione Civile website reported (March 23, 2020) that 63,927 cases are currently infected with SARS-CoV-2. No formal sample size calculation was made for this project but, on the basis of data available to date, considering the prevalence of hematological patients in Italy (0.4%) and assuming that these patients have the same risk of contracting COVID-19 as the general population, we supposed to enroll at least 250 patients (at March 24, 2020).

Statistical analyses All data collected will be summarized using appropriate descriptive statistics: absolute and relative frequencies for discrete variables; mean, standard deviation, median and interquartile range for continuous ones. To identify factors significantly associated with composite endpoint, log-binomial regression will be used for modelling risk ratio together with 95% confidence interval estimated.

The least absolute shrinkage and selection operator (LASSO) method will be applied for selecting the factors able to independently predict primary end-point. LASSO selects variables correlates to the measured outcome by shrinking coefficients weights, down to zero for the ones not correlated to outcome. In addition, machine learning techniques will be used for validating results from LASSO. A weight will be assigned to each coefficient of the selected predictors and weights will be summed to produce a total aggregate score. Predictive performance will be assessed through discrimination and calibration. Discrimination indicates how well the model can distinguish individuals with the outcome from those without the outcome. Two, the net reclassification improvement (NRI) will be calculated for assessing the 'net' number of individuals correctly reclassified using "the new model" over a comparator index \[i.e., CCI (Charlson Comorbidity Score) or MCS (Multisource Comorbidity Score), or HM-disease specific\]. Calibration ascertains the concordance between the model's predictions and observed outcomes, which we evaluated using a calibration plot. Cartographic and geostatistical methods will be used to exploring the spatial patterns of disease. An Exploratory Spatial Data Analysis (ESDA) and the Kriging method will be also applied to describe and model spatial (geographical) pattern.

Eligibility criteria: Inclusion Criteria:

* Age equal to or greater than 18 years of age.
* History of hematological malignancies (acute leukemias, myelodysplastic syndromes, myeloproliferative neoplasms, lymphomas, myeloma).
* Active hematological malignancies (acute leukemias, myelodysplastic syndromes, myeloproliferative neoplasms, lymphomas, myeloma) at any stage/status.
* SARS-CoV-2 positive test (nasopharyngeal, BAL, fecal), documented by Real-Time Reverse Transcriptase (RT)-PCR Diagnostic Panels.

Exclusion Criteria:

* Hematological diseases, other than hematological malignancies.
* SARS-CoV-2 negative test.

Primary outcomes:
measure: To evaluate mortality.
timeFrame: At 2 months from study initiation
measure: To evaluate potential predictive biochemical parameters of mortality.
timeFrame: At 2 months from study initiation
measure: To evaluate potential predictive HM-related parameters of mortality.
timeFrame: At 2 months from study initiation
measure: To evaluate COVID severity as predictive parameter of mortality.
timeFrame: At 2 months from study initiation
Secondary outcomes:
measure: Epidemiology of patients with HM infected by SARS-CoV-2with any spectrum of illness severity
timeFrame: At 6 months from study initiation
measure: Definition of complete clinical picture of COVID-19 in HM
timeFrame: At 2 months from study initiation
measure: Evolution of HM
timeFrame: At 2 months from study initiation
measure: To evaluate admission to ICU requiring mechanical ventilation or death per characteristics
timeFrame: At 2 months from study initiation
measure: Viral dynamics in infected HM patients
timeFrame: At 12 months from study initiation
Other outcomes:
Locations:
city: Alessandria
country: Italy
facility: SC Ematologia Ospedale SS Antonio e Biagio e Cesare Arrigo
city: Ancona
country: Italy
facility: UOC Ematologia, Ospedali Riuniti
city: Ascoli Piceno
country: Italy
facility: UOC Ematologia e Terapia Cellulare, Ospedale Mazzoni
city: Aviano
country: Italy
facility: SC Oncologia Medica, CRO
city: Bari
country: Italy
facility: SC Ematologia, Policlinico Bari
city: Bari
country: Italy
facility: UOC Ematologia, I.R.C.C.S Istituto Tumori Giovanni Paolo II
city: Biella
country: Italy
facility: SSD Ematologia, Ospedale degli Infermi
city: Bologna
country: Italy
facility: UOC Ematologia, Azienda Ospedaliero-Universitaria Policlinico S.Orsola-Malpighi,
city: Bolzano
country: Italy
facility: Ematologia e Centro Trapianto Midollo Osseo, Ospedale di Bolzano
city: Brescia
country: Italy
facility: UO Ematologia e CTMO, ASST Spedali Civili
city: Brescia
country: Italy
facility: UO Ematologia e CTMO, ASST Spedali Civili
city: Busto Arsizio
country: Italy
facility: UOC Onco-Ematologia ASST Valle Olona
city: Cagliari
country: Italy
facility: SC Ematologia e CTMO AZIENDA OSPEDALIERA "G. BROTZU" - OSPEDALE ONCOLOGICO BUSINCO
city: Catania
country: Italy
facility: UOC Ematologia, AOU Policlinico Vittorio Emanuele
city: Como
country: Italy
facility: Ematologia, Ospedale Valduce
city: Cosenza
country: Italy
facility: UOC Ematologia, Azienda Ospedaliera di Cosenza
city: Cremona
country: Italy
facility: UO Ematologia e CTMO, ASST Cremona
city: Cuneo
country: Italy
facility: SC Ematologia Ospedale S. Croce
city: Ferrara
country: Italy
facility: UOC, Ematologia Azienda Ospedaliero Universitaria Arcispedale S. Anna
city: Firenze
country: Italy
facility: S.O.D. Ematologia, Azienda Ospedaliero Universitaria Careggi
city: Foggia
country: Italy
facility: UOC Ematologia, Policlinico Ospedali Riuniti
city: Forlì
country: Italy
facility: IRST-IRCC di Meldola
city: Genova
country: Italy
facility: UO Ematologia, Ospedale Policlinico S.Martino IRCCS
city: Genova
country: Italy
facility: UO Ematologia, Ospedale Policlinico San Martino
city: Lecce
country: Italy
facility: UOC di Ematologia e Trapianto di Cellule Staminali, P.O. Vito Fazzi
city: Legnano
country: Italy
facility: UOC di Ematologia, Ospedale di Legnano
city: Livorno
country: Italy
facility: UO Dipartimento di Ematologia, USL 6
city: Lodi
country: Italy
facility: UOC Oncologia ASST Lodi
city: Messina
country: Italy
facility: UOC Ematologia Azienda Ospedaliera Universitaria "G.Martino"
city: Mestre
country: Italy
facility: UO Ematologia, Ospedale dell'Angelo di Mestre
city: Milano
country: Italy
facility: Ematologia, IEO
city: Milano
country: Italy
facility: SC Ematologia, Istituto Nazionale dei Tumori
city: Milano
country: Italy
facility: SC Ematologia, Ospedale Niguarda
city: Milano
country: Italy
facility: UO Ematologia, IRCCS Ospedale San Raffaele
city: Milano
country: Italy
facility: UO Servizio di Ematologia e Medicina Trasfusionale, Ospedale Luigi Sacco
city: Milano
country: Italy
facility: UOC Ematologia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
city: Modena
country: Italy
facility: UO Ematologia Policlinico di Modena
city: Monza
country: Italy
facility: UOC Ematologia, Ospedale S. Gerardo
city: Napoli
country: Italy
facility: SC Ematologia Istituto Nazionale Tumori - IRCCS "Fondazione G. Pascale",
city: Napoli
country: Italy
facility: UOC Ematologia e Trapianti di Midollo, AOU Federico II
city: Napoli
country: Italy
facility: UOC Ematologia, Ospedale Antonio Cardarelli
city: Novara
country: Italy
facility: UOC Ematologia, Azienda Ospedaliero-Universitaria Maggiore della Carità
city: Orbassano
country: Italy
facility: Ospedale san Luigi Gonzaga
city: Padova
country: Italy
facility: Ematologia Azienda Ospedaliera di Padova
city: Palermo
country: Italy
facility: UO Ematologia, Policlinico Paolo Giaccone
city: Parma
country: Italy
facility: UOC Ematologia e CTMO, Azienda Ospedaliero-Universitaria di Parma
city: Pavia
country: Italy
facility: SC Ematologia, Fondazione IRCCS Policlinico San Matteo
city: Perugia
country: Italy
facility: SC Ematologia e Trapianto di Midollo Osseo, Azienda Ospedaliera di Perugia
city: Pesaro
country: Italy
facility: UO Ematologia e CTMO, Azienda Ospedaliera Ospedali Riuniti
city: Pescara
country: Italy
facility: UOC di Ematologia, Ospedale Civile Spirito Santo
city: Piacenza
country: Italy
facility: UO Ematologia e CTMO, Presidio Ospedaliero di Piacenza
city: Pisa
country: Italy
facility: UO Ematologia, AOU Pisana- Santa Chiara
city: Ravenna
country: Italy
facility: UO Ematologia dell'Ospedale Santa Maria delle Croci
city: Reggio Calabria
country: Italy
facility: UOC Ematologia, Grande Ospedale Metropolitano Bianchi-Melacrino-Morelli
city: Reggio Emilia
country: Italy
facility: SC Ematologia, Arcispedale Santa Maria Nuova
city: Rimini
country: Italy
facility: UO Ematologia, Ospedale Infermi
city: Roma
country: Italy
facility: AOU Azienda Ospedaliera Universitaria Sant'Andrea
city: Roma
country: Italy
facility: IFO - Ematologia e Trapianto Cellule -Istituto Nazionale del Cancro di Regina Elena
city: Roma
country: Italy
facility: SC Ematologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS
city: Roma
country: Italy
facility: UO Ematologia e Trapianti di Cellule Staminali, A.O. S. Camillo-Forlanini
city: Roma
country: Italy
facility: UO Ematologia, Policlinico Tor Vergata
city: Roma
country: Italy
facility: UOC Ematologia e trapianto di cellule staminali, Policlinico Universitario Campus Bio-Medico
city: Roma
country: Italy
facility: UOC Ematologia Policlinico Umberto I
city: Roma
country: Italy
facility: UOC Ematologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS
city: Roma
country: Italy
facility: UOC Ematologia- Azienda Ospedaliera San Giovanni Addolorata
city: Rozzano
country: Italy
facility: UO Ematologia, Istituto Clinico Humanitas
city: Salerno
country: Italy
facility: UOC Ematologia e centro trapianti cellule staminali emopoietiche, AOU San Giovanni Di Dio e Ruggi D'aragona
city: Sanremo
country: Italy
facility: Ematologia ASL Imperiese
city: Savona
country: Italy
facility: Medicina Interna ed Ematologia, Asl 1
city: Siena
country: Italy
facility: UOC Ematologia, Policlinico Santa Maria alle Scotte
city: Taranto
country: Italy
facility: UOC Ematologia e Trapianto Midollo Osseo, Ospedale S. G. Moscati
city: Torino
country: Italy
facility: SCDU Ematologia e terapie cellulari, Ospedale Mauriziano Umberto I
city: Torino
country: Italy
facility: UO Ematologia, Ospedale Universitario Molinette San Giovanni Battista
city: Torino
country: Italy
facility: UO Ematologia, Ospedale Universitario Molinette San Giovanni Battista
city: Treviso
country: Italy
facility: UO Ematologia, Ospedale Civili Ca' Foncello
city: Trieste
country: Italy
facility: SC Ematologia, Azienda sanitaria universitaria Giuliano Isontina
city: Udine
country: Italy
facility: Clinica Ematologia, Azienda Ospedaliera-Universitaria Santa Maria della Misericordia
city: Varese
country: Italy
facility: UOC Ematologia, ASST Sette Laghi, Osp. Di Circolo e Fondazione Macchi
city: Verona
country: Italy
facility: UOC Ematologia, Azienda Ospedaliera Integrata di Verona
city: Verona
country: Italy
facility: UOC Ematologia, Azienda Ospedaliera Integrata di Verona
city: Vicenza
country: Italy
facility: UOC Ematologia, Ospedale San Bortolo
Study officials:
affiliation: Ospedale di Circolo e Fondazione Macchi, ASST Sette Laghi, Varese, Italy
name: Francesco Passamonti, MD
role: PRINCIPAL_INVESTIGATOR
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