Sponsor decision

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 blood cell distribution width (RDW) ≥17%) identified by machine learning in the polycythemia vera advanced integrated model (PV-AIM) project in the real-life setting.

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 period 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 to 40 sites in Germany. If necessary, the study will be extended to other countries to achieve the target population.

Key Inclusion criteria

1. Signed informed consent must be obtained prior to participation in the study

2. Patients ≥18 years

3. Confirmed diagnosis of Polycythemia vera (according to WHO 2008, 2016, or 2022 criteria) (Tefferi and Vardiman 2008, Arber et al 2016, Khoury et al 2022)

4. Eastern Cooperative Oncology Group (ECOG) ≤ 2

5. No previous pharmacologic cytoreductive therapy (including investigational drugs)

6. No phlebotomy in last 14 days

7. 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):

       • Increase in spleen size or symptomatic splenomegaly
       • Platelet increase to > 1,000,000/µl
       • WBC increase to > 15,000/µl or higher
       • Frequent (> 10 per year) or increasing frequency of phlebotomies

     • Increasing risk of thromboembolism and bleeding:

       • New thromboembolism and/or hemorrhagic complications
       • Microcirculation disorders despite acetyl salicylic acid (ASA) 2x 100 mg/day
       • Restricted feasibility or intolerance of phlebotomies
       • Symptomatic iron deficiency
       • Uncontrolled increase in hematocrit
       • Severe or distressing disease-related symptoms

8. Female participants of childbearing potential should have a negative serum pregnancy test within 72 hours prior to receiving the first dose of study treatment.

Key Exclusion criteria

1. Patients with post-polycythemia vera myelofibrosis (post-PV MF) or accelerated phase/ blast phase myeloproliferative neoplasm acute myeloid leukemia (AP/BP-MPN AML).
2. 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).
3. Patients with rare hereditary galactose intolerance, total lactase deficiency or glucose-galactose malabsorption in their past medical history.
4. Active uncontrolled infection that is considered by the Investigator as a reason for exclusion.
5. Active malignancies (except for carcinoma in situ; prostate cancer and breast cancer in remission and - where necessary - ongoing hormonal therapy).
6. 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.
7. 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.
8. Sexually active males unwilling to use a condom during intercourse while taking study treatment and for at least 3 months after stopping study treatment.
9. HIV patients treated with nucleoside reverse transcriptase inhibitors like didanosine and stavudine.

Other inclusion/exclusion criteria may apply

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com