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:
- 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