COVID19-hematological Malignancies: the Italian Hematology Alliance

SARS-CoV-2 Infection Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04352556
• Other study ID #: HM-COVID19-Italy
• Status: Recruiting
• Start date: April 7, 2020
• Est. completion date: October 1, 2022

Study information

• Verified date: September 2022
• Source: Ospedale di Circolo - Fondazione Macchi
• Contact: Francesco Passamonti, MD
• Phone: +39-0332-393648
• Email: francesco.passamonti[@]asst-settelaghi.it
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 250
• Est. completion date: October 1, 2022
• Est. primary completion date: October 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• COVID-19
• Hematologic Neoplasms
• Hematological Malignancies
• Infections
• Neoplasms
• SARS-CoV-2 Infection

Locations

Country	Name	City	State
Italy	SC Ematologia Ospedale SS Antonio e Biagio e Cesare Arrigo	Alessandria
Italy	UOC Ematologia, Ospedali Riuniti	Ancona
Italy	UOC Ematologia e Terapia Cellulare, Ospedale Mazzoni	Ascoli Piceno
Italy	SC Oncologia Medica, CRO	Aviano
Italy	SC Ematologia, Policlinico Bari	Bari
Italy	UOC Ematologia, I.R.C.C.S Istituto Tumori Giovanni Paolo II	Bari
Italy	SSD Ematologia, Ospedale degli Infermi	Biella
Italy	UOC Ematologia, Azienda Ospedaliero-Universitaria Policlinico S.Orsola-Malpighi,	Bologna
Italy	Ematologia e Centro Trapianto Midollo Osseo, Ospedale di Bolzano	Bolzano
Italy	UO Ematologia e CTMO, ASST Spedali Civili	Brescia
Italy	UO Ematologia e CTMO, ASST Spedali Civili	Brescia
Italy	UOC Onco-Ematologia ASST Valle Olona	Busto Arsizio
Italy	SC Ematologia e CTMO AZIENDA OSPEDALIERA "G. BROTZU" - OSPEDALE ONCOLOGICO BUSINCO	Cagliari
Italy	UOC Ematologia, AOU Policlinico Vittorio Emanuele	Catania
Italy	Ematologia, Ospedale Valduce	Como
Italy	UOC Ematologia, Azienda Ospedaliera di Cosenza	Cosenza
Italy	UO Ematologia e CTMO, ASST Cremona	Cremona
Italy	SC Ematologia Ospedale S. Croce	Cuneo
Italy	UOC, Ematologia Azienda Ospedaliero Universitaria Arcispedale S. Anna	Ferrara
Italy	S.O.D. Ematologia, Azienda Ospedaliero Universitaria Careggi	Firenze
Italy	UOC Ematologia, Policlinico Ospedali Riuniti	Foggia
Italy	IRST-IRCC di Meldola	Forlì
Italy	UO Ematologia, Ospedale Policlinico S.Martino IRCCS	Genova
Italy	UO Ematologia, Ospedale Policlinico San Martino	Genova
Italy	UOC di Ematologia e Trapianto di Cellule Staminali, P.O. Vito Fazzi	Lecce
Italy	UOC di Ematologia, Ospedale di Legnano	Legnano
Italy	UO Dipartimento di Ematologia, USL 6	Livorno
Italy	UOC Oncologia ASST Lodi	Lodi
Italy	UOC Ematologia Azienda Ospedaliera Universitaria "G.Martino"	Messina
Italy	UO Ematologia, Ospedale dell'Angelo di Mestre	Mestre
Italy	Ematologia, IEO	Milano
Italy	SC Ematologia, Istituto Nazionale dei Tumori	Milano
Italy	SC Ematologia, Ospedale Niguarda	Milano
Italy	UO Ematologia, IRCCS Ospedale San Raffaele	Milano
Italy	UO Servizio di Ematologia e Medicina Trasfusionale, Ospedale Luigi Sacco	Milano
Italy	UOC Ematologia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico	Milano
Italy	UO Ematologia Policlinico di Modena	Modena
Italy	UOC Ematologia, Ospedale S. Gerardo	Monza
Italy	SC Ematologia Istituto Nazionale Tumori - IRCCS "Fondazione G. Pascale",	Napoli
Italy	UOC Ematologia e Trapianti di Midollo, AOU Federico II	Napoli
Italy	UOC Ematologia, Ospedale Antonio Cardarelli	Napoli
Italy	UOC Ematologia, Azienda Ospedaliero-Universitaria Maggiore della Carità	Novara
Italy	Ospedale san Luigi Gonzaga	Orbassano
Italy	Ematologia Azienda Ospedaliera di Padova	Padova
Italy	UO Ematologia, Policlinico Paolo Giaccone	Palermo
Italy	UOC Ematologia e CTMO, Azienda Ospedaliero-Universitaria di Parma	Parma
Italy	SC Ematologia, Fondazione IRCCS Policlinico San Matteo	Pavia
Italy	SC Ematologia e Trapianto di Midollo Osseo, Azienda Ospedaliera di Perugia	Perugia
Italy	UO Ematologia e CTMO, Azienda Ospedaliera Ospedali Riuniti	Pesaro
Italy	UOC di Ematologia, Ospedale Civile Spirito Santo	Pescara
Italy	UO Ematologia e CTMO, Presidio Ospedaliero di Piacenza	Piacenza
Italy	UO Ematologia, AOU Pisana- Santa Chiara	Pisa
Italy	UO Ematologia dell'Ospedale Santa Maria delle Croci	Ravenna
Italy	UOC Ematologia, Grande Ospedale Metropolitano Bianchi-Melacrino-Morelli	Reggio Calabria
Italy	SC Ematologia, Arcispedale Santa Maria Nuova	Reggio Emilia
Italy	UO Ematologia, Ospedale Infermi	Rimini
Italy	AOU Azienda Ospedaliera Universitaria Sant'Andrea	Roma
Italy	IFO - Ematologia e Trapianto Cellule -Istituto Nazionale del Cancro di Regina Elena	Roma
Italy	SC Ematologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Roma
Italy	UO Ematologia e Trapianti di Cellule Staminali, A.O. S. Camillo-Forlanini	Roma
Italy	UO Ematologia, Policlinico Tor Vergata	Roma
Italy	UOC Ematologia e trapianto di cellule staminali, Policlinico Universitario Campus Bio-Medico	Roma
Italy	UOC Ematologia Policlinico Umberto I	Roma
Italy	UOC Ematologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Roma
Italy	UOC Ematologia- Azienda Ospedaliera San Giovanni Addolorata	Roma
Italy	UO Ematologia, Istituto Clinico Humanitas	Rozzano
Italy	UOC Ematologia e centro trapianti cellule staminali emopoietiche, AOU San Giovanni Di Dio e Ruggi D'aragona	Salerno
Italy	Ematologia ASL Imperiese	Sanremo
Italy	Medicina Interna ed Ematologia, Asl 1	Savona
Italy	UOC Ematologia, Policlinico Santa Maria alle Scotte	Siena
Italy	UOC Ematologia e Trapianto Midollo Osseo, Ospedale S. G. Moscati	Taranto
Italy	SCDU Ematologia e terapie cellulari, Ospedale Mauriziano Umberto I	Torino
Italy	UO Ematologia, Ospedale Universitario Molinette San Giovanni Battista	Torino
Italy	UO Ematologia, Ospedale Universitario Molinette San Giovanni Battista	Torino
Italy	UO Ematologia, Ospedale Civili Ca' Foncello	Treviso
Italy	SC Ematologia, Azienda sanitaria universitaria Giuliano Isontina	Trieste
Italy	Clinica Ematologia, Azienda Ospedaliera-Universitaria Santa Maria della Misericordia	Udine
Italy	UOC Ematologia, ASST Sette Laghi, Osp. Di Circolo e Fondazione Macchi	Varese
Italy	UOC Ematologia, Azienda Ospedaliera Integrata di Verona	Verona
Italy	UOC Ematologia, Azienda Ospedaliera Integrata di Verona	Verona
Italy	UOC Ematologia, Ospedale San Bortolo	Vicenza

Sponsors (1)

Lead Sponsor	Collaborator
Ospedale di Circolo - Fondazione Macchi

Country where clinical trial is conducted

Italy, 

References & Publications (5)

Corrao G, Rea F, Di Martino M, De Palma R, Scondotto S, Fusco D, Lallo A, Belotti LMB, Ferrante M, Pollina Addario S, Merlino L, Mancia G, Carle F. Developing and validating a novel multisource comorbidity score from administrative data: a large population-based cohort study from Italy. BMJ Open. 2017 Dec 26;7(12):e019503. doi: 10.1136/bmjopen-2017-019503. — View Citation

Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, Liu L, Shan H, Lei CL, Hui DSC, Du B, Li LJ, Zeng G, Yuen KY, Chen RC, Tang CL, Wang T, Chen PY, Xiang J, Li SY, Wang JL, Liang ZJ, Peng YX, Wei L, Liu Y, Hu YH, Peng P, Wang JM, Liu JY, Chen Z, Li G, Zheng ZJ, Qiu SQ, Luo J, Ye CJ, Zhu SY, Zhong NS; China Medical Treatment Expert Group for Covid-19. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020 Apr 30;382(18):1708-1720. doi: 10.1056/NEJMoa2002032. Epub 2020 Feb 28. — View Citation

Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, Wang W, Song H, Huang B, Zhu N, Bi Y, Ma X, Zhan F, Wang L, Hu T, Zhou H, Hu Z, Zhou W, Zhao L, Chen J, Meng Y, Wang J, Lin Y, Yuan J, Xie Z, Ma J, Liu WJ, Wang D, Xu W, Holmes EC, Gao GF, Wu G, Chen W, Shi W, Tan W. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020 Feb 22;395(10224):565-574. doi: 10.1016/S0140-6736(20)30251-8. Epub 2020 Jan 30. — View Citation

Wang H, Zhang L. Risk of COVID-19 for patients with cancer. Lancet Oncol. 2020 Apr;21(4):e181. doi: 10.1016/S1470-2045(20)30149-2. Epub 2020 Mar 3. — View Citation

Xia Y, Jin R, Zhao J, Li W, Shen H. Risk of COVID-19 for patients with cancer. Lancet Oncol. 2020 Apr;21(4):e180. doi: 10.1016/S1470-2045(20)30150-9. Epub 2020 Mar 3. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To evaluate mortality.	The percentage of HM patients with COVID-19 who died.	At 2 months from study initiation
Primary	To evaluate potential predictive biochemical parameters of mortality.	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.	At 2 months from study initiation
Primary	To evaluate potential predictive HM-related parameters of mortality.	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.	At 2 months from study initiation
Primary	To evaluate COVID severity as predictive parameter of mortality.	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	At 2 months from study initiation
Secondary	Epidemiology of patients with HM infected by SARS-CoV-2with any spectrum of illness severity	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)	At 6 months from study initiation
Secondary	Definition of complete clinical picture of COVID-19 in HM	Characterization of clinical and biochemical profile of patients with SARS-CoV-2 positivity.	At 2 months from study initiation
Secondary	Evolution of HM	Assessment of HM status post SARS-CoV-2 infection stratified as no implication, loss of response, progression of the hematological disease.	At 2 months from study initiation
Secondary	To evaluate admission to ICU requiring mechanical ventilation or death per characteristics	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).	At 2 months from study initiation
Secondary	Viral dynamics in infected HM patients		At 12 months from study initiation