COVID19-hematological Malignancies: the Italian Hematology Alliance

Sponsor

Ospedale di Circolo - Fondazione Macchi (Other)

Overall Status

Recruiting

CT.gov ID

NCT04352556

Collaborator

(none)

250

Enrollment

Locations

24.7

Anticipated Duration (Months)

3.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
SARS-CoV-2 Infection Hematological Malignancies

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.

Study Design

Study Type:

Observational

Anticipated Enrollment :

250 participants

Observational Model:

Cohort

Time Perspective:

Other

Official Title:

SARS-CoV-2 Infection in Patients With Hematological Malignancies: the Italian Hematology Alliance

Actual Study Start Date :

Apr 7, 2020

Anticipated Primary Completion Date :

Apr 30, 2022

Anticipated Study Completion Date :

Apr 30, 2022

Outcome Measures

Primary Outcome Measures

To evaluate mortality. [At 2 months from study initiation]
The percentage of HM patients with COVID-19 who died.
To evaluate potential predictive biochemical parameters of mortality. [At 2 months from study initiation]
We will assess the correlation between some biochemical parameters at diagnosis of COVID (i.e. hemoglobin, platelets, lymphocytes, clotting tests, CRP), each on the basis of its specific unit of measure, and mortality.
To evaluate potential predictive HM-related parameters of mortality. [At 2 months from study initiation]
We will assess the correlation between HM-related parameters at diagnosis of COVID [i.e. disease type (leukemia, lymphomas, myeloma), disease status (remission / stable / progression), therapy status (on / off therapy)] and mortality.
To evaluate COVID severity as predictive parameter of mortality. [At 2 months from study initiation]
We will assess the correlation between COVID severity [mild (non-pneumonia and mild pneumonia), severe (dyspnea, respiratory frequency ≥ 30/min, SpO2 ≤ 93%, PaO2/FiO2 < 300 and/or lung infiltrates > 50%) and critical (respiratory failure, septic shock, and/or multiple organ disfunction or failure)] and mortality

Secondary Outcome Measures

Epidemiology of patients with HM infected by SARS-CoV-2with any spectrum of illness severity [At 6 months from study initiation]
Description of the different types of hematological malignancies (WHO criteria) in patients with SARS-CoV-2 infection. All aggregated data will be stratified on the basis of COVID severity: mild (non-pneumonia and mild pneumonia), severe (dyspnea, respiratory frequency ≥ 30/min, SpO2 ≤ 93%, PaO2/FiO2 < 300 and/or lung infiltrates > 50%) and critical disease (respiratory failure, septic shock, and/or multiple organ disfunction or failure)
Definition of complete clinical picture of COVID-19 in HM [At 2 months from study initiation]
Characterization of clinical and biochemical profile of patients with SARS-CoV-2 positivity.
Evolution of HM [At 2 months from study initiation]
Assessment of HM status post SARS-CoV-2 infection stratified as no implication, loss of response, progression of the hematological disease.
To evaluate admission to ICU requiring mechanical ventilation or death per characteristics [At 2 months from study initiation]
Percentage of HM patients being admitted to ICU requiring mechanical ventilation, or death stratified per disease type, status, per off-therapy/on-therapy, per type of therapy (chemo, immunotherapy, cell therapy, stem cell transplant).
Viral dynamics in infected HM patients [At 12 months from study initiation]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	SC Ematologia Ospedale SS Antonio e Biagio e Cesare Arrigo	Alessandria	Italy
2	UOC Ematologia, Ospedali Riuniti	Ancona	Italy
3	UOC Ematologia e Terapia Cellulare, Ospedale Mazzoni	Ascoli Piceno	Italy
4	SC Oncologia Medica, CRO	Aviano	Italy
5	SC Ematologia, Policlinico Bari	Bari	Italy
6	UOC Ematologia, I.R.C.C.S Istituto Tumori Giovanni Paolo II	Bari	Italy
7	SSD Ematologia, Ospedale degli Infermi	Biella	Italy
8	UOC Ematologia, Azienda Ospedaliero-Universitaria Policlinico S.Orsola-Malpighi,	Bologna	Italy
9	Ematologia e Centro Trapianto Midollo Osseo, Ospedale di Bolzano	Bolzano	Italy
10	UO Ematologia e CTMO, ASST Spedali Civili	Brescia	Italy
11	UO Ematologia e CTMO, ASST Spedali Civili	Brescia	Italy
12	UOC Onco-Ematologia ASST Valle Olona	Busto Arsizio	Italy
13	SC Ematologia e CTMO AZIENDA OSPEDALIERA "G. BROTZU" - OSPEDALE ONCOLOGICO BUSINCO	Cagliari	Italy
14	UOC Ematologia, AOU Policlinico Vittorio Emanuele	Catania	Italy
15	Ematologia, Ospedale Valduce	Como	Italy
16	UOC Ematologia, Azienda Ospedaliera di Cosenza	Cosenza	Italy
17	UO Ematologia e CTMO, ASST Cremona	Cremona	Italy
18	SC Ematologia Ospedale S. Croce	Cuneo	Italy
19	UOC, Ematologia Azienda Ospedaliero Universitaria Arcispedale S. Anna	Ferrara	Italy
20	S.O.D. Ematologia, Azienda Ospedaliero Universitaria Careggi	Firenze	Italy
21	UOC Ematologia, Policlinico Ospedali Riuniti	Foggia	Italy
22	IRST-IRCC di Meldola	Forlì	Italy
23	UO Ematologia, Ospedale Policlinico S.Martino IRCCS	Genova	Italy
24	UO Ematologia, Ospedale Policlinico San Martino	Genova	Italy
25	UOC di Ematologia e Trapianto di Cellule Staminali, P.O. Vito Fazzi	Lecce	Italy
26	UOC di Ematologia, Ospedale di Legnano	Legnano	Italy
27	UO Dipartimento di Ematologia, USL 6	Livorno	Italy
28	UOC Oncologia ASST Lodi	Lodi	Italy
29	UOC Ematologia Azienda Ospedaliera Universitaria "G.Martino"	Messina	Italy
30	UO Ematologia, Ospedale dell'Angelo di Mestre	Mestre	Italy
31	Ematologia, IEO	Milano	Italy
32	SC Ematologia, Istituto Nazionale dei Tumori	Milano	Italy
33	SC Ematologia, Ospedale Niguarda	Milano	Italy
34	UO Ematologia, IRCCS Ospedale San Raffaele	Milano	Italy
35	UO Servizio di Ematologia e Medicina Trasfusionale, Ospedale Luigi Sacco	Milano	Italy
36	UOC Ematologia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico	Milano	Italy
37	UO Ematologia Policlinico di Modena	Modena	Italy
38	UOC Ematologia, Ospedale S. Gerardo	Monza	Italy
39	SC Ematologia Istituto Nazionale Tumori - IRCCS "Fondazione G. Pascale",	Napoli	Italy
40	UOC Ematologia e Trapianti di Midollo, AOU Federico II	Napoli	Italy
41	UOC Ematologia, Ospedale Antonio Cardarelli	Napoli	Italy
42	UOC Ematologia, Azienda Ospedaliero-Universitaria Maggiore della Carità	Novara	Italy
43	Ospedale san Luigi Gonzaga	Orbassano	Italy
44	Ematologia Azienda Ospedaliera di Padova	Padova	Italy
45	UO Ematologia, Policlinico Paolo Giaccone	Palermo	Italy
46	UOC Ematologia e CTMO, Azienda Ospedaliero-Universitaria di Parma	Parma	Italy
47	SC Ematologia, Fondazione IRCCS Policlinico San Matteo	Pavia	Italy
48	SC Ematologia e Trapianto di Midollo Osseo, Azienda Ospedaliera di Perugia	Perugia	Italy
49	UO Ematologia e CTMO, Azienda Ospedaliera Ospedali Riuniti	Pesaro	Italy
50	UOC di Ematologia, Ospedale Civile Spirito Santo	Pescara	Italy
51	UO Ematologia e CTMO, Presidio Ospedaliero di Piacenza	Piacenza	Italy
52	UO Ematologia, AOU Pisana- Santa Chiara	Pisa	Italy
53	UO Ematologia dell'Ospedale Santa Maria delle Croci	Ravenna	Italy
54	UOC Ematologia, Grande Ospedale Metropolitano Bianchi-Melacrino-Morelli	Reggio Calabria	Italy
55	SC Ematologia, Arcispedale Santa Maria Nuova	Reggio Emilia	Italy
56	UO Ematologia, Ospedale Infermi	Rimini	Italy
57	AOU Azienda Ospedaliera Universitaria Sant'Andrea	Roma	Italy
58	IFO - Ematologia e Trapianto Cellule -Istituto Nazionale del Cancro di Regina Elena	Roma	Italy
59	SC Ematologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Roma	Italy
60	UO Ematologia e Trapianti di Cellule Staminali, A.O. S. Camillo-Forlanini	Roma	Italy
61	UO Ematologia, Policlinico Tor Vergata	Roma	Italy
62	UOC Ematologia e trapianto di cellule staminali, Policlinico Universitario Campus Bio-Medico	Roma	Italy
63	UOC Ematologia Policlinico Umberto I	Roma	Italy
64	UOC Ematologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Roma	Italy
65	UOC Ematologia- Azienda Ospedaliera San Giovanni Addolorata	Roma	Italy
66	UO Ematologia, Istituto Clinico Humanitas	Rozzano	Italy
67	UOC Ematologia e centro trapianti cellule staminali emopoietiche, AOU San Giovanni Di Dio e Ruggi D'aragona	Salerno	Italy
68	Ematologia ASL Imperiese	Sanremo	Italy
69	Medicina Interna ed Ematologia, Asl 1	Savona	Italy
70	UOC Ematologia, Policlinico Santa Maria alle Scotte	Siena	Italy
71	UOC Ematologia e Trapianto Midollo Osseo, Ospedale S. G. Moscati	Taranto	Italy
72	SCDU Ematologia e terapie cellulari, Ospedale Mauriziano Umberto I	Torino	Italy
73	UO Ematologia, Ospedale Universitario Molinette San Giovanni Battista	Torino	Italy
74	UO Ematologia, Ospedale Universitario Molinette San Giovanni Battista	Torino	Italy
75	UO Ematologia, Ospedale Civili Ca' Foncello	Treviso	Italy
76	SC Ematologia, Azienda sanitaria universitaria Giuliano Isontina	Trieste	Italy
77	Clinica Ematologia, Azienda Ospedaliera-Universitaria Santa Maria della Misericordia	Udine	Italy
78	UOC Ematologia, ASST Sette Laghi, Osp. Di Circolo e Fondazione Macchi	Varese	Italy	21100
79	UOC Ematologia, Azienda Ospedaliera Integrata di Verona	Verona	Italy
80	UOC Ematologia, Azienda Ospedaliera Integrata di Verona	Verona	Italy
81	UOC Ematologia, Ospedale San Bortolo	Vicenza	Italy