Clinical trial NCT05853458: Evaluation of HU-resistance in Adult Patients With Polycythemia Vera Who Meet PV-AIM Predictors
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Polycythemia Vera
Keywords: Polycythemia vera (PV)
Hydroxyurea
Resistance
Intolerance
Predictive parameters
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2023-05-10
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: From 6 to 9 months after start of de novo HU-treatment
Secondary outcomes:
measure: Proportion of PV patients who meet the PV-AIM HU-resistance predictors before start of HU-treatment
timeFrame: Baseline
measure: Proportion of patients developing HU resistance/intolerance at any time within the maximum treatment period of 15 months
timeFrame: Up to 15 months
measure: Proportion of "non-switchers"
timeFrame: Up to 15 months
measure: Timepoint of therapy switch (after confirmation of HU resistance/intolerance)
timeFrame: Up to 15 months
measure: Reasons for therapy switch / non-switch
timeFrame: Up to 15 months
measure: Therapies applied during follow-up period
timeFrame: Up to 3 months after treatment discontinuation
Other outcomes:
Locations:
city: Heidelberg
country: Germany
facility: Novartis Investigative Site
state: Baden Wuerttemberg
city: Kronach
country: Germany
facility: Novartis Investigative Site
state: Bayern
city: Straubing
country: Germany
facility: Novartis Investigative Site
state: Bayern
city: Langen
country: Germany
facility: Novartis Investigative Site
state: Hessen
city: Goslar
country: Germany
facility: Novartis Investigative Site
state: Niedersachsen
city: Lingen Ems
country: Germany
facility: Novartis Investigative Site
state: Niedersachsen
city: Aachen
country: Germany
facility: Novartis Investigative Site
state: Nordrhein Westfalen
city: Dortmund
country: Germany
facility: Novartis Investigative Site
state: Nordrhein-Westfalen
city: Koeln
country: Germany
facility: Novartis Investigative Site
state: Nordrhein-Westfalen
city: Velbert
country: Germany
facility: Novartis Investigative Site
state: North Rhine-Westphalia
city: Halle Saale
country: Germany
facility: Novartis Investigative Site
state: Sachsen-Anhalt
city: Luebeck
country: Germany
facility: Novartis Investigative Site
state: Schleswig-Holstein
city: Augsburg
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Bonn
country: Germany
facility: Novartis Investigative Site
city: Donauwoerth
country: Germany
facility: Novartis Investigative Site
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: Erding
country: Germany
facility: Novartis Investigative Site
city: Erfurt
country: Germany
facility: Novartis Investigative Site
city: Gera
country: Germany
facility: Novartis Investigative Site
city: Guetersloh
country: Germany
facility: Novartis Investigative Site
city: Hannover
country: Germany
facility: Novartis Investigative Site
city: Kiel
country: Germany
facility: Novartis Investigative Site
city: Koeln
country: Germany
facility: Novartis Investigative Site
city: Merseburg
country: Germany
facility: Novartis Investigative Site
city: Moers
country: Germany
facility: Novartis Investigative Site
city: Mutlangen
country: Germany
facility: Novartis Investigative Site
city: Naunhof
country: Germany
facility: Novartis Investigative Site
city: Offenburg
country: Germany
facility: Novartis Investigative Site
city: Saarbruecken
country: Germany
facility: Novartis Investigative Site
city: Torgau
country: Germany
facility: Novartis Investigative Site
city: Westerstede
country: Germany
facility: Novartis Investigative Site
city: Wuerselen
country: Germany
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: