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

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.

Study Overview

• Status: Recruiting
• Conditions: Primary Myelofibrosis (PMF); Post Essential Thrombocythaemia Myelofibrosis (PET-MF); Post Polycythemia Myelofibrosis (PPV MF)
• Intervention / Treatment: Drug: Ropeginterferon alfa-2b (BESREMi®)

Detailed Description

Ropeginterferon alfa 2b is administered subcutaneously once every 2 weeks. Ruxolitinib is self-administered orally as part of standard of care. BSubjects will continue combination treatment through the Initial Treatment Period (ITP) (first 6 cycles), which includes a Qualification Assessment. Those deriving clinical benefit in the opinion of the treating physician may continue receiving combination treatment in the Additional Treatment Period (6 cycles). Qualification Assessments will be performed at the end of each Additional Treatment Period, which is iterative, and may repeat for as long as clinical benefit is sustained, at the discretion of the treating physician.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hainder Gill, MD; Phone Number: 852 22555859; Email: gillhsh@hku.hk

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Recruiting
    • Department of Medicine, Queen Mary Hospital
    • Principal Investigator: Harinder Gill, MD
    • Contact: Harinder Gill, MD; Phone Number: 852 22555859; Email: gillhsh@hku.hk

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 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 Criteria:

Subjects will not be eligible for participation if they meet any of the following exclusion criteria:

• 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

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: Ropeginterferon alfa 2b; Ropeginterferon alfa 2b is administered subcutaneously once every 2 weeks in addition to standard of care with Ruxolitinib which will be self-administered orally as described below. Both medications will continue uninterrupted in 28-day cycles. Subjects will continue combination treatment through the Initial Treatment Period (ITP) (first 6 cycles), which includes a Qualification Assessment. Those deriving clinical benefit in the opinion of the treating physician may continue receiving combination treatment in the Additional Treatment Period (6 cycles). Qualification Assessments will be performed at the end of each Additional Treatment Period, which is iterative, and may repeat for as long as clinical benefit is sustained, at the discretion of the treating physician.

Drug: Ropeginterferon 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Enumeration and description of adverse events (AEs), including determination of dose limiting toxicities (DLTs), serious adverse events (SAEs), and other AEs	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Spleen volume change at 24 weeks	Proportion of patients who experience a spleen length reduction by palpation of ≥30% OR spleen volume reduction (SVR) of ≥35% by MRI or CT by 24 weeks of treatment	24 weeks
Symptom response at 24 weeks	Proportion of patients who describe a ≥50% reduction in symptom burden by the myelofibrosis symptom assessment form (MFSAF) by 24 weeks of treatment. The MFSAF has a scale of 0-70 where a higher score indicates worse outcome.	24 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of molecular responses	Changes in allelic burden of JAK2V617F, MPL, CALR or other driver mutations will be assessed. A molecular responses is assessed using the International Working Group of Myeloproliferative Neoplasm Research and Treatment Criteria.	24 months
Rate of morphologic response	Changes in bone marrow morphology (cellularity, erythroid, myeloid, megakaryocyte, reticulin and fibrosis) during treatment. Response is assessed using the International Working Group of Myeloproliferative Neoplasm Research and Treatment Criteria.	24 months

Collaborators and Investigators

• Sponsor: The University of Hong Kong
• Investigators: Principal Investigator: Harinder Gill, MD, The University of Hong Kong

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: December 20, 2024
• First Submitted That Met QC Criteria: January 7, 2025
• First Posted (Actual): January 13, 2025

Study Record Updates

• Last Update Posted (Actual): June 11, 2025
• Last Update Submitted That Met QC Criteria: June 9, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Ruxolitinib; Myelofibrosis; Ropeginterferon alfa 2b; Ruxolitinib failiure
• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders; Bone Marrow Diseases; Hemorrhagic Disorders; Blood Platelet Disorders; Myeloproliferative Disorders; Thrombocytosis; Thrombocythemia, Essential; Polycythemia; Primary Myelofibrosis
• Other Study ID Numbers: P1101RUXMF

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No