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

Polycythemia Vera Clinical Trial

— HU-F-AIM  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05853458
• Other study ID #: CINC424BDE15
• Secondary ID: 2022-502338-20-0
• Status: Recruiting
• Phase: Phase 4
• Start date: July 28, 2023
• Est. completion date: December 31, 2026

Study information

• Verified date: June 2024
• Source: Novartis
• Contact: Novartis Pharmaceuticals
• Phone: +41613241111
• Email: novartis.email[@]novartis.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: December 31, 2026
• Est. primary completion date: September 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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

Related Conditions & MeSH terms

• Polycythemia
• Polycythemia Vera

Intervention

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

Locations

Country	Name	City	State
Germany	Novartis Investigative Site	Augsburg
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Bonn
Germany	Novartis Investigative Site	Donauwoerth
Germany	Novartis Investigative Site	Dortmund	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Erding
Germany	Novartis Investigative Site	Erfurt
Germany	Novartis Investigative Site	Gera
Germany	Novartis Investigative Site	Halle
Germany	Novartis Investigative Site	Hannover
Germany	Novartis Investigative Site	Heidelberg	Baden-Wuerttemberg
Germany	Novartis Investigative Site	Kiel
Germany	Novartis Investigative Site	Koeln
Germany	Novartis Investigative Site	Köln
Germany	Novartis Investigative Site	Kronach
Germany	Novartis Investigative Site	Langen	Hessen
Germany	Novartis Investigative Site	Lingen	Niedersachsen
Germany	Novartis Investigative Site	Luebeck	Schleswig-Holstein
Germany	Novartis Investigative Site	Merseburg
Germany	Novartis Investigative Site	Moers
Germany	Novartis Investigative Site	Mutlangen
Germany	Novartis Investigative Site	Naunhof
Germany	Novartis Investigative Site	Offenburg
Germany	Novartis Investigative Site	Straubing	Bayern
Germany	Novartis Investigative Site	Torgau
Germany	Novartis Investigative Site	Velbert	North Rhine-Westphalia
Germany	Novartis Investigative Site	Westerstede
Germany	Novartis Investigative Site	Wuerselen

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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