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

Overview

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

Description

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.

Eligibility

Inclusion Criteria:

1. Signed informed consent must be obtained prior to participation in the study
2. Confirmed diagnosis of Polycythemia vera (according to WHO 2008, 2016, or 2022 criteria)
3. Eastern Cooperative Oncology Group (ECOG) ≤ 2
4. No previous pharmacologic cytoreductive therapy (including investigational drugs)
5. No phlebotomy in last 28 days
6. 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:
7. 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:

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 skin cancer; prostate cancer and breast cancer in remission and - where necessary - ongoing hormonal therapy)
6. Inadequate liver function as assessed by Investigator
7. 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
8. 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.
9. Sexually active males unwilling to use a condom during intercourse while taking study treatment and for at least 6 months after stopping study treatment.
10. HIV patients treated with nucleoside reverse transcriptase inhibitors like didanosine and stavudine

Other inclusion/exclusion criteria may apply