Study to Identify and Describe Predictive Factors for Thromboembolic Events in Patients With High-risk Polycythemia Vera (Prospero)

Prospective Observational Study to Identify and Describe Predictive Factors for Thromboembolic Events in Patients With High-risk Polycythemia Vera

This is a prospective observational study that will enroll patients with high-risk Polycythemia Vera (PV) with at least one Thromboembolic Event (TE) after diagnosis or up to 2 years prior to diagnosis.

This is a non-randomized study, and to ensure a sufficient number of patients in both cohorts, enrollment in each cohort will be terminated once the target of 150 patients has been reached.

Study Overview

• Status: Recruiting
• Conditions: Polycythemia Vera
• Intervention / Treatment: Other: Hydroxyurea; Other: Ruxolitinib

Detailed Description

All patients are already on treatment with hydroxyurea or ruxolitinib at enrollment as per clinical practice and independently of their participation in this study. In addition, the follow-up visits and the evaluation procedures required in the study protocol correspond to current clinical practice. According to local regulations related to observational studies, assessments such as blood tests are justified by the purpose and rationale of the study (i.e., the identification of possible predictive factors of TEs) and are considered current clinical practice. Data related to other procedures will be collected only if such procedures are performed as per clinical practice but are not required otherwise.

Patients in both cohorts will be followed for 3 years after enrollment and will have visits at Months 6, 12, 18, 24, 30 and 36. A time window of ± 1 month is permitted for all visits.

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

• Study Contact: Name: Novartis Pharmaceuticals; Phone Number: +41613241111; Email: novartis.email@novartis.com
• Study Contact Backup: Name: Novartis Pharmaceuticals

Study Locations

• Italy
  • Napoli, Italy, 80131
    • Recruiting
    • Novartis Investigative Site
  • Napoli, Italy, 80132
    • Recruiting
    • Novartis Investigative Site
  • AL
    • Alessandria, AL, Italy, 15100
      • Recruiting
      • Novartis Investigative Site
  • AN
    • Ancona, AN, Italy, 60126
      • Recruiting
      • Novartis Investigative Site
  • BA
    • Bari, BA, Italy, 70124
      • Recruiting
      • Novartis Investigative Site
  • BO
    • Bologna, BO, Italy, 40138
      • Recruiting
      • Novartis Investigative Site
  • CO
    • Como, CO, Italy, 22100
      • Recruiting
      • Novartis Investigative Site
  • CS
    • Cosenza, CS, Italy, 87100
      • Recruiting
      • Novartis Investigative Site
  • CT
    • Catania, CT, Italy, 95123
      • Recruiting
      • Novartis Investigative Site
  • FI
    • Firenze, FI, Italy, 50134
      • Recruiting
      • Novartis Investigative Site
  • GE
    • Genova, GE, Italy, 16132
      • Recruiting
      • Novartis Investigative Site
  • LE
    • Lecce, LE, Italy, 73100
      • Recruiting
      • Novartis Investigative Site
    • Tricase, LE, Italy, 73039
      • Recruiting
      • Novartis Investigative Site
  • MB
    • Monza, MB, Italy, 20900
      • Recruiting
      • Novartis Investigative Site
  • MI
    • Milano, MI, Italy, 20122
      • Recruiting
      • Novartis Investigative Site
  • PA
    • Palermo, PA, Italy, 90127
      • Recruiting
      • Novartis Investigative Site
    • Palermo, PA, Italy, 90146
      • Recruiting
      • Novartis Investigative Site
  • PC
    • Piacenza, PC, Italy, 29100
      • Recruiting
      • Novartis Investigative Site
  • PD
    • Padova, PD, Italy, 35100
      • Recruiting
      • Novartis Investigative Site
  • PI
    • Pisa, PI, Italy, 56126
      • Recruiting
      • Novartis Investigative Site
  • PR
    • Parma, PR, Italy, 43100
      • Recruiting
      • Novartis Investigative Site
  • RC
    • Reggio Calabria, RC, Italy, 89124
      • Recruiting
      • Novartis Investigative Site
  • RE
    • Reggio Emilia, RE, Italy, 42100
      • Recruiting
      • Novartis Investigative Site
  • RM
    • Roma, RM, Italy, 00189
      • Recruiting
      • Novartis Investigative Site
    • Roma, RM, Italy, 00161
      • Recruiting
      • Novartis Investigative Site
    • Roma, RM, Italy, 00168
      • Recruiting
      • Novartis Investigative Site
    • Roma, RM, Italy, 00144
      • Recruiting
      • Novartis Investigative Site
  • SA
    • Pagani, SA, Italy, 84016
      • Recruiting
      • Novartis Investigative Site
  • TO
    • Orbassano, TO, Italy, 10043
      • Recruiting
      • Novartis Investigative Site
    • Torino, TO, Italy, 10126
      • Recruiting
      • Novartis Investigative Site
  • TR
    • Terni, TR, Italy, 05100
      • Recruiting
      • Novartis Investigative Site
  • VA
    • Varese, VA, Italy, 21100
      • Recruiting
      • Novartis Investigative Site
  • VI
    • Vicenza, VI, Italy, 36100
      • Recruiting
      • Novartis Investigative Site
  • VR
    • Verona, VR, Italy, 37126
      • Recruiting
      • Novartis Investigative Site
  • VT
    • Viterbo, VT, Italy, 01033
      • Recruiting
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study will involve patients in Italy with high-risk Polycythemia Vera

Description

Inclusion Criteria:

1. Signed informed consent must be obtained prior to participation in the study.
2. Age ≥18 years.
3. Diagnosis of PV according to WHO 2008 or WHO 2016 and high-risk stratification according to European LeukemiaNet (ELN) classification.
4. At least one TE after diagnosis or up to 2 years prior to diagnosis.
5. Patients on treatment with hydroxyurea at enrollment and for at least 18 months prior to enrollment or those on treatment with ruxolitinib who started treatment up to 18 months before enrollment.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Hydroxyurea; Patients being treated with hydroxyurea at enrollment and for at least 18 months prior to enrollment. Patients may switch to ruxolitinib treatment during the study in case of inadequate response or intolerance.	Other: Hydroxyurea; Prospective observational study. There is no treatment allocation. Patients prescribed with Hydroxyurea are eligible to enroll into this study.
Ruxolitinib; Patients on treatment with ruxolitinib who started treatment up to 18 months prior to enrollment.	Other: Ruxolitinib; Prospective observational study. There is no treatment allocation. Patients prescribed with Ruxolitinib are eligible to enroll into this study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of abnormalities presented in patients with Thromboembolic Events (TEs) during the follow up	Demographics, blood pressure, laboratory blood tests, and use of antiplatelets and/or anticoagulants are predictors of TE occurrence, a univariate Cox regression model for repeated events will be applied for each predictor considering all the TEs occurring within 12 months and the time from baseline to each occurrence. Predictors found statistically significant at the 5% level will then be considered in a multivariate Cox regression model for repeated events.	Up to 36 months
Blood pressure	Blood pressure is going to be collected	Up to month 36
Number of patients with abnormal Body Mass Index (BMI)	Number of patients with abnormal Body Mass Index (BMI) will be collected	Up to month 36
Number of patients with abnormal weight	Number of patients with abnormal weight will be collected	Up to month 36
Number of patients with abnormal Neutrophil (NEP) count	Number of patients with abnormal Neutrophil (NEP) count will be collected	Up to 36 months
Number of patients with abnormal White blood Count (WBC)	Number of patients with abnormal White blood Count (WBC) will be collected	Up to 36 months
Number of patients with abnormal Lymphocytes (LYP) count	Number of patients with abnormal Lymphocytes (LYP) count will be collected	Up to 36 months
Number of participants using antiplatelets and/or anticoagulants on the incidence of TEs	Number of participants using antiplatelets and/or anticoagulants on the incidence of Thromboembolic Events (TEs) will be collected	Up to 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Synergistic combinations of predictive factors	Synergistic combinations of predictive factors (Red cell Distribution Width, neutrophils, lymphocytes, neutrophil/ lymphocyte ratio and platelets). Synergy score is defined as the product of the individual significances of variable 1 and 2 (expected) divided by the significance of the two-variable model (observed) To investigate cases of extreme synergy, instances in which two variables split the given cohort into high-risk and low-risk patients are far better than either variable alone. A simple synergy scoring metric to rank variable in terms of synergy (S):S12=(P1*P2)/P12 where P1 and P2 are the maximum possible (Cox regression derived) p-values for variable 1 and variable 2 and P12 was the max. p-value possible from the combination of variables 1 and 1. This synergy is intended to capture a variable that may provide exclusive non-redundant information when attempting to split a cohort based on risk and may provide an added insight into the functional/clinical rationale of a model	Up to 36 months
Yearly incidence of TEs	Yearly incidence of Thromboembolic Events (TEs) will be collected	36 months
Incidence of arterial and venous TEs in the hydroxyurea and ruxolitinib cohorts	Incidence of arterial and venous TEs in the hydroxyurea and ruxolitinib cohorts will be collected	36 months
Incidence and severity of adverse events	Incidence and severity of adverse events according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0.	36 months

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): March 2, 2023
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2026

Study Registration Dates

• First Submitted: September 16, 2022
• First Submitted That Met QC Criteria: September 16, 2022
• First Posted (Actual): September 21, 2022

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 14, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Ruxolitinib; hydroxyurea; NIS; polycythemia vera; Italy; PV; predictive factors; high-risk polycythemia vera; TE
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Neoplasms; Neoplasms by Site; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Embolism and Thrombosis; Bone Marrow Neoplasms; Hematologic Neoplasms; Thromboembolism; Polycythemia Vera; Polycythemia; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Antisickling Agents; Hydroxyurea
• Other Study ID Numbers: CINC424BIT01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO