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

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05853458

Collaborator

(none)

300

Enrollment

Arm

29.6

Anticipated Duration (Months)

Study Details

Study Description

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 cell distribution width (RDW) ≥17%) identified by machine learning in the polycythemia vera advanced integrated model (PV-AIM) project in the real-life setting

Condition or Disease	Intervention/Treatment	Phase
Polycythemia Vera	Drug: Hydroxyurea	Phase 4

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 Design

Study Type:

Interventional

Anticipated Enrollment :

300 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Jun 15, 2023

Anticipated Primary Completion Date :

Sep 30, 2024

Anticipated Study Completion Date :

Dec 1, 2025

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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. [From 6 to 9 months after start of de novo 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).

Secondary Outcome Measures

Proportion of PV patients who meet the PV-AIM HU-resistance predictors before start of HU-treatment [Baseline]
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).
Proportion of patients developing HU resistance/intolerance at any time within the maximum treatment period of 15 months [Up to 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).
Proportion of "non-switchers" [Up to 15 months]
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).
Timepoint of therapy switch (after confirmation of HU resistance/intolerance) [Up to 15 months]
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.
Reasons for therapy switch / non-switch [Up to 15 months]
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
Therapies applied during follow-up period [Up to 3 months after treatment discontinuation]
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 99 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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