Secondary Cancers in Myeloproliferative Neoplasms (MPN-K Study)

Sponsor

Fondazione per la Ricerca Ospedale Maggiore (Other)

Overall Status

Completed

CT.gov ID

NCT03745378

Collaborator

(none)

1,881

Enrollment

Locations

4.5

Actual Duration (Months)

62.7

Patients Per Site

13.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The incidence of secondary cancer (SC) in patients with myeloproliferative neoplasms (MPN) is high and comparable to that of thrombosis. However, the identification of patient subgroups that might be at increased susceptibility of developing SC has not been systematically addressed. This international case-control study (MPN-K) is aimed to elucidate the prognostic role of JAK2V617F mutation in predicting the occurrence of SC in patients with classical MPN, polycythemia vera (PV), essential thrombocythemia (ET) and myelofibrosis (MF)

Condition or Disease	Intervention/Treatment	Phase
Polycythemia Vera Essential Thrombocythemia Myelofibrosis	Other: JAK2V617F mutation

Detailed Description

For each recruited case with concomitant diagnosis of myeloproliferative neoplasms (MPN) and secondary cancer each participating center will provide up 3 control patients (1 control for each case could be accepted but the optimal number is 3). Controls are patients with myeloproliferative neoplasms and no history of cancer. Each control will be matched to the paired case for sex, age (+/- 3 years), date of MPN diagnosis (+/- 5 years), and MPN disease duration (+/- 3 years).

Each control is censored at the date of the secondary cancer occurrence in his matched case (index date).

Data will be collected retrospectively from pre-existing medical records and reported by each center on a web-based and validated eCRF developed to record y all study data. In order to maintain patient privacy, all data records will be treated anonymously and no personal data to identify patient will be recorded: patients will be identified in the study by an alphanumeric code.

Study Design

Study Type:

Observational

Actual Enrollment :

1881 participants

Observational Model:

Case-Control

Time Perspective:

Retrospective

Official Title:

Secondary Cancers in Myeloproliferative Neoplasms (MPN-K Study)

Actual Study Start Date :

May 15, 2018

Actual Primary Completion Date :

Jul 7, 2018

Actual Study Completion Date :

Sep 30, 2018

Arms and Interventions

Arm	Intervention/Treatment
Cases Patients with diagnosis of Myeloproliferative Neoplasms (MPN) including Polycythemia Vera, Essential thrombocytopenia or Myelofibrosis, exposed or not exposed to JAK2V617F mutation, who experienced secondary cancer(s) diagnosed at presentation of MPN or during the course of the myeloproliferative disease.	Other: JAK2V617F mutation JAK2 V617F is attached to the cytosolic juxtamembrane region of dimeric cytokine receptors, such as EpoR or MPL (TpoR); The JAK2V617F mutation results from a guanine to thymine change at nucleotide 1849 of the cDNA, in exon 14 of the gene. This valine is located at one of the predicted interfaces between JH1 and JH2 domains,
Controls Patients with diagnosis of Myeloproliferative Neoplasms (MPN) including Polycythemia Vera, Essential thrombocytopenia or Myelofibrosis, exposed or not exposed to JAK2V617F mutation, without history of secondary cancer.	Other: JAK2V617F mutation JAK2 V617F is attached to the cytosolic juxtamembrane region of dimeric cytokine receptors, such as EpoR or MPL (TpoR); The JAK2V617F mutation results from a guanine to thymine change at nucleotide 1849 of the cDNA, in exon 14 of the gene. This valine is located at one of the predicted interfaces between JH1 and JH2 domains,

Arm

Intervention/Treatment

Cases

Patients with diagnosis of Myeloproliferative Neoplasms (MPN) including Polycythemia Vera, Essential thrombocytopenia or Myelofibrosis, exposed or not exposed to JAK2V617F mutation, who experienced secondary cancer(s) diagnosed at presentation of MPN or during the course of the myeloproliferative disease.

Other: JAK2V617F mutation

JAK2 V617F is attached to the cytosolic juxtamembrane region of dimeric cytokine receptors, such as EpoR or MPL (TpoR); The JAK2V617F mutation results from a guanine to thymine change at nucleotide 1849 of the cDNA, in exon 14 of the gene. This valine is located at one of the predicted interfaces between JH1 and JH2 domains,

Controls

Other: JAK2V617F mutation

Outcome Measures

Primary Outcome Measures

Number of patients with secondary cancers after diagnosis of Polycythemia Vera (PV), Essential Trombocythemia (ET) and Myelofibrosis (MF) [10 year from diagnosis of PV, ET or MF]
The ratio of number of patients showing JAK2V617F mutation on the number of patients not exposed to this mutation will be calculated in the group of subjects experiencing second cancer after diagnosis of PV, ET and MF (defined as 'cases') and related (odds ratio) with the ratio of patients exposed on those not exposed to JAK2V617F mutation in the group of subjects with no experience of secondary cancers after diagnosis of PV, ET and MF (this group is defined as 'Control' group)

Secondary Outcome Measures

Number of patients with secondary cancers after diagnosis of Polycythemia Vera (PV), Essential Trombocythemia (ET) and Myelofibrosis (MF) in subgroups of subjects exposed to potential risk factors at diagnosis [10 year from diagnosis of PV, ET or MF]
Characteristics at diagnosis of patients with PV, ET and MF (including other mutations) with occurrence of second cancers (SC) are decribed and compared with those not experiencing SC after diagnosis of myloproliferative neoplasm; the ratio of number of patients exposed to potential risk factors on the number of subjects not exposed will be calculated in the group cases (as defined for primary outcome measure) and related (odds ratio) with the ratio of patient exposed versus not exposed calculated in the subgroup of control.
Number of patients with secondary cancers after diagnosis of Polycythemia Vera (PV), Essential Trombocythemia (ET) and Myelofibrosis (MF) in the subgroups exposed to treatment [10 year from diagnosis of PV, ET or MF]
Group of patients exposed and not exposed to different class of treatments for PV, ET and MF are compared and related in the group of cases and control

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Diagnosis of Philadelphia-negative Myeloproliferative Neoplasms (MPN) according to

PVSG, 2008 and 2016 WHO criteria, including:

Polycythemia Vera (PV)
Essential Thrombocythemia (ET)
Myelofibrosis (MF), including both primary and secondary MF
Diagnosis performed between 1st January 2000 to 31 December 2016
Diagnosis of secondary cancer(s) performed concurrently or subsequently the diagnosis of MPN

Exclusion Criteria:

Diagnosis of cancer occurred before the diagnosis of MPN (PV, ET, MF)

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Palacky University and University Hospital Olomouc, Faculty of Medecine	Olomouc	Czechia
2	University Hospital RWTH - Department Oncology, Hematology, Hemostaeseology and stem cell transplantation	Aachen	Germany
3	Johannes Wesling Academic Medical Center	Minden	Germany
4	Meir Medical Center	Kfar Saba	Israel
5	Azienda Sanitaria di Asti - A.S.L. AT Ospedale Cardinal Massaia - S.C. Oncologia	Asti	Italy	14100
6	ASST- Papa Giovanni XXIII - UOC Ematologia	Bergamo	Italy	24127
7	Ospedale S. Orsola - Malpighi - UO Ematologia	Bologna	Italy	40138
8	U.O. Emostasi "G. Rodolico" Dipartimento di Scienze Mediche, Chirurgiche e Tecnologiche Avanzate "G.F. Ingrassia" Università degli Studi di Catania	Catania	Italy	95123
9	Azienda Ospedaliera S. Croce e Carle di Cuneo- Divisione di Ematologia,	Cuneo	Italy	2100
10	AOU Careggi di Firenze CRIMM- Center of Research and Innovation of Myeloproliferative Neoplasms - Department of Experimental and Clinical Medicine, University of Florence	Firenze	Italy	50134
11	Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico - UOC Ematologia	Milano	Italy	20122
12	IRCCS Ospedale San Raffaele Unità Operativa di Ematologia e Trapianto Midollo Osseo	Milano	Italy	20132
13	ASST MONZA Ospedale San Gerardo Clinica Ematologica	Monza	Italy	20900
14	Azienda Ospedaliera Universitaria Federico II di Napoli Divisione di Ematologia e Trapianti del Midollo	Napoli	Italy	80131
15	Azienda Ospedaliero Universitaria Maggiore della Carità di Novara SCDU Ematologia	Novara	Italy	28100
16	Fondazione IRCCS Policlinico San Matteo S.C Ematologia	Pavia	Italy	27100
17	AUSL IRCCS di Reggio Emilia Presidio Osp. Arcispedale Santa Maria Nuova - Unità Ematologia	Reggio Emilia	Italy	42123
18	Fondazione Policlinico Universitario A. Gemelli IRCCS UCSC Ematologia	Roma	Italy	00168
19	A.O.U. Città della Salute e della Scienza di Torino - Ospedale Molinette- S.C. Ematologia	Torino	Italy	10126
20	A.O.U. Città della Salute e della Scienza di Torino Ospedale Molinette - S.C. Ematologia U	Torino	Italy	10126
21	Ospedale Borgo Roma - Unità di Ematologia	Verona	Italy	37134
22	Ospedale San Bortolo di Vicenza - U.O.C di Ematologia	Vicenza	Italy	36100
23	Hospital Clinic, Hematology Department	Barcellona	Spain	08034
24	Hospital del Mar - Haematologia Clinica	Barcelona	Spain
25	Hospital Universitario Vall d' Hebron - Unit Hematology	Barcelona	Spain
26	University Clinical Hospital of Santiago De Campostela - Service of Hematology	Santiago De Compostela	Spain
27	Hospita Clinico Universitario - Hematology Department	Valencia	Spain
28	Miguel Servet University Hospital	Zaragoza	Spain
29	Belfast Health and Social Care Trust - Unit Haematology	Belfast	United Kingdom
30	Guy's and St Thomas' NHS Foundation Trust	London	United Kingdom