RecruitingPhase 2NCT06770842

Ropeginterferon Alfa 2b Plus Ruxolitinib for Myelofibrosis

Safety and Efficacy of Ropeginterferon Alfa-2b in Combination With Ruxolitinib in Patients With Myelofibrosis Demonstrating Suboptimal Response to Ruxolitinib Monotherapy

Sponsor

The University of Hong Kong

Enrollment

20 participants

Start Date

Mar 1, 2025

Study Type

INTERVENTIONAL

Conditions

Primary myelofibrosis (PMF)Post Polycythemia Myelofibrosis (PPV MF)Post Essential Thrombocythaemia Myelofibrosis (PET-MF)

Summary

In this open-label single arm phase 2 study, approximately 20 patients with MF demonstrating suboptimal response to ruxolitinib monotherapy will be enrolled. Patients will continue to receive ruxolitinib at a stable dose and ropeginterferon alfa 2b will be added to the regimen.

Eligibility

Min Age: 18 Years

Inclusion Criteria12

Willing and able to provide informed consent
Age ≥18 years
Diagnosis of Overt Myelofibrosis (primary, post-ET, or post-PV) per World Health Organization (WHO) 2022 diagnostic criteria
Intermediate-1, Intermediate-2, or high-risk disease by Dynamic International Prognostic Scoring System (DIPSS)
Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
Platelet count ≥75 x 109/L prior to dosing on Cycle 1 Day 1
Absolute neutrophil count ≥0.5 x 109/L prior to dosing on Cycle 1 Day 1
Peripheral blast count ≤10% prior to dosing on Cycle 1 Day 1
Women of childbearing potential and fertile men must agree to use an approved method of contraception from screening until 30 days after the last dose of ropeginterferon and ruxolitinib.
Patients with suboptimal response to ruxolitinib as per one of the below:
i. Relapsed: Ruxolitinib treatment for ≥3 months with spleen regrowth, defined as <10% SVR or <30% decrease in spleen size from baseline, following an initial response* ii. Refractory: Ruxolitinib treatment for ≥3 months with <10% SVR or <30% decrease in spleen size from baseline.
* Response to ruxolitinib is defined as a ≥35% reduction in spleen volume from baseline, or a ≥50% reduction in spleen size for baseline spleen sizes >10 cm below left costal margin (LCM); a non-palpable spleen for baseline spleen sizes between 5-10 cm below LCM; or not eligible for spleen response for baseline spleen <5 cm below LCM.

Exclusion Criteria18

Prior or current use of interferon alfa (IFNα) preparations for MPN
Patients currently on other investigational therapy (ies)
Contraindications or hypersensitivity to IFNα preparations
History of organ and haematopoietic stem cell transplantation
History of splenectomy
Pregnant or lactating females, or females planning to become pregnant at any time during the study
Documented autoimmune disease at screening
Infection with human immunodeficiency virus (HIV)
Active and uncontrolled infections with hepatitis B virus (HBV) and hepatitis C virus (HCV). Please note that patients on antiviral therapy with undetectable HBV DNA and HCV RNA may be recruited.
Evidence of severe retinopathy including but not limited to macular degeneration, diabetic retinopathy and hypertensive retinopathy.
History of clinically significant neuropsychiatric conditions including but not limited to depression and epilepsy.
Clinically significant neuropsychiatric conditions including but not limited to depression and epilepsy.
Concurrent second active and non-stable malignancy (patients with a concurrent second active but stable malignancy, i.e., non-melanoma skin cancers, are eligible)
Evidence of alcohol or drug abuse within 6 months
Evidence at the time of Screening of significant renal or hepatic insufficiency (unless due to hemolysis) as defined by any of the following local lab parameters:
Calculated glomerular filtration rate (GFR; using the Cockcroft-Gault equation) <40 mL/min or serum creatinine >1.5 x the local upper limit of normal
Aspartate transaminase (AST) or alanine aminotransferase (ALT) ≥2.5 x the local upper limit of normal
Unwilling or unable to comply with the study protocol

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Interventions

DRUGRopeginterferon alfa-2b (BESREMi®)

Ropeginterferon alfa 2b is administered subcutaneously once every 2 weeks. The dosing will be 250mcg at Week 0, 350mcg at Week 2, 500mcg at Week 4, and 500mcg every 2 weeks thereafter