Ropeginterferon for High Risk JAK2 Clonal Hematopoiesis

NCT07249840 | Not Yet Recruiting Phase 1 FDA Drug

• 1 other identifier: 25-566
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn if the drug ropeginterferon alfa-2b can be used safely to treat patients with a JAK2 mutation and high risk features, but do not yet have a myeloproliferative neoplasm. The main questions it aims to answer are:

• Can we enroll 12 patients with JAK2 mutations and high risk features without a myeloproliferative neoplasm on a clinical trial evaluating the drug ropeginterferon?
• Is ropeginterferon safe to use in these patients? Participants will:
• Receive ropeginterferon as an injection under the skin once every 4 weeks
• Visit the clinic every 1-3 months for checkups and tests

Conditions

JAK2 Mutation

Keywords

Clonal hematopoiesis; CHIP; JAK2; Myeloproliferative neoplasm

Outcome Measures

Primary Outcomes (2)

• Number of patients consented and enrolled within 2 years of study opening

  Primary outcome is feasibility, or feasibility of enrolling 12 patients with high-risk JAK2 clonal hematopoiesis onto a clinical trial with ropeginterferon treatment within 2 years of study opening.

  2 years

• Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

  Safety and tolerability of ropeginterferon in patients with JAK2 clonal hematopoiesis and high-risk features.

  2 years

Secondary Outcomes (5)

• Number of patients with decrease of JAK2 V617F variant allele fraction to undetectable levels if baseline VAF was <10% or decrease of JAK2 V617F VAF by at least 50% if baseline VAF was >10%

  2 years

• Rates of arterial and venous thrombosis

  2 years

• Rates of bleeding

  2 years

• Patient reported quality of life as measured by the Patient's Impression of Global Change (PGIC) and Patient-Reported Outcomes Measurement Information System 29-item Health Profile (PROMIS-29)

  2 years

• Rates of progression to overt MPN

  2 years

Study Arms (1)

Ropeginterferon

EXPERIMENTAL

Drug: Ropeginterferon

Interventions

Ropeginterferon DRUG

Patients will receive Ropeginterferon

Ropeginterferon

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults age 18 years or older
• Evidence of JAK2 V617F clonal hematopoiesis of indeterminate potential, as defined by a JAK2 V617F mutation detected on quantitative PCR. By definition, these patients do NOT have a diagnosis of an MPN, and must have at least one additional high-risk feature.
• Have high-risk clinical/laboratory features, as defined as at least ONE of the following criteria:
• Patients with a venous or arterial thrombotic event within 1 year of diagnosis of JAK2 clonal hematopoiesis
• Patients with elevated laboratory parameters above normal limits at screening, but not meeting criteria for an MPN by WHO 2016 criteria. This would include patients with elevated laboratory parameters but an otherwise normal bone marrow biopsy.
• White blood cell count \> 10 K/uL OR
• Hemoglobin \> 16 g/dL in women and \> 16.5 g/dL in men; hematocrit \>48% for women and \>49% for men OR
• Platelets \>400 K/uL
• Patients with JAK2 VAF \>20%
• Willing to have a bone marrow biopsy at study entry to exclude an MPN diagnosis. Screening bone marrow biopsy must not be diagnostic of any overt hematologic malignancy by morphologic assessment and must be consistent with a diagnosis of clonal hematopoiesis as determined by multi-institutional hematopathology review. A historical bone marrow biopsy is allowed if within 3 months of study entry and records and pathology can be obtained. In cases where the bone marrow biopsy results are uncertain, study eligibility should be discussed with the PI. Patients with increased red blood cell parameters or concerning diagnosis for PV should also have an erythropoietin level drawn to assess for a PV diagnosis by WHO 2016 criteria.
• Must have adequate organ function as demonstrated by the following:
• ALT (SGPT) and/or AST (SGOT) ≤ 2.5x upper limit of normal (ULN), or ≤ 4x ULN (if upon judgment of the treating physician, it is believed to be due to extramedullary hematopoiesis \[EMH\] related to MF);
• Direct bilirubin ≤ 1.5 x ULN; or ≤ 2x ULN (if upon judgment of the treating physician, it is believed to be due to extramedullary hematopoiesis \[EMH\] related to MF);
• eGFR \>60 mL/min
• leukocytes ≥3,000/mcL

You may not qualify if:

• Meeting WHO 2016 criteria for a MPN.
• Pregnant or lactating.
• Known history of human immunodeficiency virus (HIV), hepatitis C, or hepatitis B.
• Any active malignancy in the past 2 years, with the exception of non-melanoma skin cancer, or cervical carcinoma in situ or breast carcinoma in situ that has been excised or resected completely and is without evidence of local recurrence or metastasis. Any malignancy treated with curative intent and no evidence for active disease in the last 2 years are eligible.
• Evidence of severe retinopathy or clinically relevant ophthalmologic disorder
• Participation in an investigational drug or device trial within 2 weeks prior to study enrolment
• Documented autoimmune disease at screening or in the medical history which is active and serious
• History of significant and clinically relevant psychiatric illnesses, including prior suicide attempts or risk of suicide on screening
• History of thyroid dysfunction not adequately controlled
• History of major organ transplantation
• History of uncontrolled severe seizure disorder
• Participants who are receiving any other investigational agents.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to ropeginterferon.

Sponsors & Collaborators

• Brigham and Women's Hospital: lead

Study Sites (1)

Mass General Brigham

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Myeloproliferative Disorders

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Central Study Contacts

Chi-Joan How

CONTACT

617-732-5190; jhow@bwh.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 16, 2025
• First Posted: November 25, 2025
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2030
• Study Completion (Estimated): June 1, 2030
• Last Updated: November 25, 2025

Record last verified: 2025-11

Locations

US (1)