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

NCT05853458 | Terminated Phase 4

• 2 other identifiers: CINC424BDE152022-502338-20-00
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 21

Brief Summary

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.

Conditions

Polycythemia Vera

Keywords

Polycythemia vera (PV); Hydroxyurea; Resistance; Intolerance; Predictive parameters

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Proportion of PV patients who meet the PV-AIM HU-resistance predictors before start of HU-treatment

  Baseline

• Proportion of patients developing HU resistance/intolerance at any time within the maximum treatment period of 15 months

  Up to 15 months

• Proportion of "non-switchers"

  Up to 15 months

• Timepoint of therapy switch (after confirmation of HU resistance/intolerance)

  Up to 15 months

• Reasons for therapy switch / non-switch

  Up to 15 months

Study Arms (1)

Hydroxyurea (HU)

EXPERIMENTAL

Participants will be treated with HU capsules, orally taken, for a maximum duration of 15 months.

Drug: Hydroxyurea

Interventions

Hydroxyurea DRUG

Hydroxyurea is commercially available in Germany and will be prescribed based on clinical judgment

Hydroxyurea (HU)

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent must be obtained prior to participation in the study
• Patients ≥18 years
• 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)
• Eastern Cooperative Oncology Group (ECOG) ≤ 2
• No previous pharmacologic cytoreductive therapy (including investigational drugs)
• No phlebotomy in last 14 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):
• 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:

You may not qualify if:

• 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 malignancies (except for carcinoma in situ; prostate cancer and breast cancer in remission and - where necessary - ongoing hormonal therapy).
• 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 3 months after stopping study treatment.
• HIV patients treated with nucleoside reverse transcriptase inhibitors like didanosine and stavudine.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (21)

Novartis Investigative Site

Heidelberg, Baden-Wurttemberg, 69115, Germany

Location

Novartis Investigative Site

Kronach, Bavaria, 96317, Germany

Location

Novartis Investigative Site

Straubing, Bavaria, 94315, Germany

Location

Novartis Investigative Site

Langen, Hesse, 63225, Germany

Location

Novartis Investigative Site

Lingen Ems, Lower Saxony, 49808, Germany

Location

Novartis Investigative Site

Aachen, North Rhine-Westphalia, 52064, Germany

Location

Novartis Investigative Site

Cologne, North Rhine-Westphalia, 50674, Germany

Location

Novartis Investigative Site

Dortmund, North Rhine-Westphalia, 44309, Germany

Location

Novartis Investigative Site

Velbert, North Rhine-Westphalia, 42551, Germany

Location

Novartis Investigative Site

Saarbrücken, Saarland, 66113, Germany

Location

Novartis Investigative Site

Merseburg, Saxony-Anhalt, 06217, Germany

Location

Novartis Investigative Site

Berlin, 10407, Germany

Location

Novartis Investigative Site

Donauwörth, 86609, Germany

Location

Novartis Investigative Site

Dresden, 01307, Germany

Location

Novartis Investigative Site

Erding, 85435, Germany

Location

Novartis Investigative Site

Gütersloh, 33332, Germany

Location

Novartis Investigative Site

Hanover, 30161, Germany

Location

Novartis Investigative Site

Kiel, 24105, Germany

Location

Novartis Investigative Site

Mutlangen, 73557, Germany

Location

Novartis Investigative Site

Naunhof, 04683, Germany

Location

Novartis Investigative Site

Würselen, 52146, Germany

Location

MeSH Terms

Conditions

Polycythemia Vera

Interventions

Hydroxyurea

Condition Hierarchy (Ancestors)

Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Myeloproliferative Disorders

Intervention Hierarchy (Ancestors)

Urea; Amides; Organic Chemicals

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 2, 2023
• First Posted: May 10, 2023
• Study Start: July 28, 2023
• Primary Completion: February 26, 2026
• Study Completion: February 26, 2026
• Last Updated: April 30, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

DE (21)