Evaluation of HU-resistance in Adult Patients With Polycythemia Vera Who Meet PV-AIM Predictors

Study Overview
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Brief Summary
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The purpose of this study is to confirm the predictive factors for hydroxyurea (HU) failure (hemoglobin (HGB) <15.5 g/dL (9.62 mmol/L) and red cell distribution width (RDW) ≥17%) identified by machine learning in the polycythemia vera advanced integrated model (PV-AIM) project in the real-life setting

Detailed Description
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This is an open-label, prospective, single arm, Phase IV interventional study to evaluate the HU-resistance/intolerance in PV patients who meet predictive parameters identified in the machine learning project PV-AIM. The study consists of three periods: screening period, treatment period (observation for HU-resistance/intolerance) and follow-up (FU) period. Eligible participants will enter the treatment period (observation for HU-resistance/intolerance) and start receiving the de novo HU treatment. The maximum treatment duration for each participant in the study will be up to 15 months. This study will be conducted in a total of 300 adult PV patients and approximately at 30 sites in Germany.

Official Title
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HU-F-AIM - A Prospective, Interventional Study to Evaluate HU-resistance in Polycythemia Vera Patients Who Meet Predictive Parameters Identified in the Machine Learning Project PV-AIM

Conditions
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Polycythemia Vera

Intervention / Treatment
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* Drug: Hydroxyurea


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent must be obtained prior to participation in the study Confirmed diagnosis of Polycythemia vera (according to WHO 2008, 2016, or 2022 criteria) Eastern Cooperative Oncology Group (ECOG) ≤ 2 No previous pharmacologic cytoreductive therapy (including investigational drugs) No phlebotomy in last 28 days HU-eligible High-risk: age ≥ 60 years and/or prior history of thrombosis Low-risk: showing at least one of the defined criteria Signs of disease progression (myeloproliferation) Increasing risk of thromboembolism and bleeding: Female participants of childbearing potential should have a negative serum pregnancy test within 72 hours prior to receiving the first dose of study treatment. Exclusion Criteria: Patients with post- polycythemia vera myelofibrosis (post-PV MF) or accelerated phase/ blast phase myeloproliferative neoplasm acute myeloid leukemia (AP/BP-MPN AML) Patients with a contraindication to HU according to the SmPC (severe bone marrow depression, leukopenia (< 2.5 x 109 leukocytes/l), thrombocytopenia (< 100 x 109 platelets/L), severe anemia (< 10 g/dL HGB) Patients with rare hereditary galactose intolerance, total lactase deficiency or glucose-galactose malabsorption in their past medical history Active uncontrolled infection that is considered by the Investigator as a reason for exclusion Active malignancies (except for skin cancer; prostate cancer and breast cancer in remission and - where necessary - ongoing hormonal therapy) Inadequate liver function as assessed by Investigator Inadequate renal function as demonstrated by Modification of Diet in Renal Disease estimate glomerular filtration rate (MDRDeGFR) < 30 mL/min/1.73m2 or on dialysis Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotrophin (hCG) laboratory test. Sexually active males unwilling to use a condom during intercourse while taking study treatment and for at least 6 months after stopping study treatment. HIV patients treated with nucleoside reverse transcriptase inhibitors like didanosine and stavudine Other inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hydroxyurea (HU)<br>Participants will be treated with HU capsules, orally taken, for a maximum duration of 15 months. | Drug: Hydroxyurea<br>* Hydroxyurea is commercially available in Germany and will be prescribed based on clinical judgment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of PV patients with HU-resistance/intolerance within 6-9 months after start of de novo HU- treatment in presence of the PV-AIM HU-resistance predictors at the start of HU treatment. | Proportion of PV participants with HU resistance/intolerance within 6-9 months after start of de novo HU treatment in presence of the PV-AIM HU resistance predictors at the start of HU treatment. The proportion will be assessed calculating the rate together with the respective 95% confidence interval (CI). | From 6 to 9 months after start of de novo HU-treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of PV patients who meet the PV-AIM HU-resistance predictors before start of HU-treatment | Proportion of PV patients who meet the PV-AIM HU-resistance predictors before start of HU-treatment. The proportion will be assessed calculating the rate together with the respective 95% confidence interval (CI). | Baseline | 
| Proportion of patients developing HU resistance/intolerance at any time within the maximum treatment period of 15 months | Proportion of patients developing HU resistance/intolerance at any time within the maximum treatment period of 15 months. The proportion will be assessed calculating the rate together with the respective 95% confidence interval (CI). | Up to 15 months | 
| Proportion of non-switchers | For all patients who develop HU resistance/intolerance according to modified European LeukemiaNet (ELN) criteria at any time during the maximum treatment period of 15 months, the proportion of non-switchers (i.e., patients remaining on HU despite they meet the HU-resistance/intolerance criteria) will be assessed. The rate will be calculated together with the respective 95% confidence interval (CI). | Up to 15 months | 
| Timepoint of therapy switch (after confirmation of HU resistance/intolerance) | For all patients who develop HU resistance/intolerance according to modified ELN criteria at any time during the maximum treatment period of 15 months, the timepoint of therapy switch (after confimration of HU resistance/intolerance) will be assessed. | Up to 15 months | 
| Reasons for therapy switch / non-switch | For all patients who develop HU resistance/intolerance according to modified ELN criteria at any time during the maximum treatment period of 15 months, the reasons for therapy switch or non-switch will be summarized | Up to 15 months | 
| Therapies applied during follow-up period | For all patients who develop HU resistance/intolerance according to modified ELN criteria at any time during the maximum treatment period of 15 months, the therapies applied during the follow-up period will be summarized | Up to 3 months after treatment discontinuation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Predictive parameters, PV, Hydroxyurea, Resistance, Intolerance