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

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

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

Study Overview

• Status: Recruiting
• Conditions: Polycythemia Vera
• Intervention / Treatment: Drug: Hydroxyurea

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Novartis Pharmaceuticals; Phone Number: +41613241111; Email: novartis.email@novartis.com
• Study Contact Backup: Name: Novartis Pharmaceuticals

Study Locations

• Germany
  • Augsburg, Germany, 86150
    • Recruiting
    • Novartis Investigative Site
  • Berlin, Germany, 10407
    • Recruiting
    • Novartis Investigative Site
  • Bonn, Germany, 53113
    • Recruiting
    • Novartis Investigative Site
  • Donauwoerth, Germany, 86609
    • Recruiting
    • Novartis Investigative Site
  • Dresden, Germany, 01307
    • Recruiting
    • Novartis Investigative Site
  • Erding, Germany, 85435
    • Recruiting
    • Novartis Investigative Site
  • Erfurt, Germany, 99085
    • Recruiting
    • Novartis Investigative Site
  • Halle, Germany, 06110
    • Recruiting
    • Novartis Investigative Site
  • Hannover, Germany, 30161
    • Recruiting
    • Novartis Investigative Site
  • Kiel, Germany, 24105
    • Recruiting
    • Novartis Investigative Site
  • Koeln, Germany, 50671
    • Recruiting
    • Novartis Investigative Site
  • Kronach, Germany, 96317
    • Recruiting
    • Novartis Investigative Site
  • Köln, Germany, 50674
    • Recruiting
    • Novartis Investigative Site
  • Merseburg, Germany, 06217
    • Recruiting
    • Novartis Investigative Site
  • Mutlangen, Germany, 73557
    • Recruiting
    • Novartis Investigative Site
  • Naunhof, Germany, 04683
    • Recruiting
    • Novartis Investigative Site
  • Offenburg, Germany, 77654
    • Recruiting
    • Novartis Investigative Site
  • Torgau, Germany, 04860
    • Recruiting
    • Novartis Investigative Site
  • Westerstede, Germany, 26655
    • Recruiting
    • Novartis Investigative Site
  • Wuerselen, Germany, 52146
    • Recruiting
    • Novartis Investigative Site
  • Baden-Wuerttemberg
    • Heidelberg, Baden-Wuerttemberg, Germany, 69115
      • Recruiting
      • Novartis Investigative Site
  • Bayern
    • Straubing, Bayern, Germany, 94315
      • Recruiting
      • Novartis Investigative Site
  • Hessen
    • Langen, Hessen, Germany, 63225
      • Recruiting
      • Novartis Investigative Site
  • Niedersachsen
    • Lingen, Niedersachsen, Germany, 49808
      • Recruiting
      • Novartis Investigative Site
  • Nordrhein-Westfalen
    • Dortmund, Nordrhein-Westfalen, Germany, 44309
      • Recruiting
      • Novartis Investigative Site
  • North Rhine-Westphalia
    • Velbert, North Rhine-Westphalia, Germany, 42551
      • Recruiting
      • Novartis Investigative Site
  • Schleswig-Holstein
    • Luebeck, Schleswig-Holstein, Germany, 23563
      • Recruiting
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): July 28, 2023
• Primary Completion (Estimated): September 30, 2024
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: May 2, 2023
• First Submitted That Met QC Criteria: May 2, 2023
• First Posted (Actual): May 10, 2023

Study Record Updates

• Last Update Posted (Actual): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 27, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Hydroxyurea; Resistance; Intolerance; PV; Predictive parameters
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Bone Marrow Neoplasms; Hematologic Neoplasms; Polycythemia Vera; Polycythemia; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Antisickling Agents; Hydroxyurea
• Other Study ID Numbers: CINC424BDE15; 2022-502338-20-00 (Other Identifier: EU CTIS number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No