Pegylated Interferon α-2b in Combination With Ruxolitinib for Treating Hydroxyurea-resistant/Intolerant PV

Phase 2RecruitingNCT05870475

Institute of Hematology & Blood Diseases Hospital, China94 enrolled

Overview

Study purpose: To compare the efficacy and safety of pegylated interferon α-2b in combination with ruxolitinib versus pegylated interferon α-2b alone for treating hydroxyurea-resistant or hydroxyurea-intolerant polycythemia vera. The subjects will be randomly divided into two groups: pegylated interferon alpha-2b combined with ruxolitinib group: pegylated interferon alpha-2b at a starting dose of 180ug will be administered subcutaneously once a week; ruxolitinib at a starting dose of 10mg will be administered orally twice daily. pegylated interferon alpha-2b group: pegylated interferon alpha-2b at a starting dose of 180ug will be administered subcutaneously once a week. If complete hematologic remission is not achieved after 12 weeks of treatment with pegylated interferon alpha-2b alone, the subject may be switched to the pegylated interferon alpha-2b combined with ruxolitinib group. If ruxolitinib is not tolerated, the subject may be switched to the pegylated interferon alpha-2b group alone.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Polycythemia Vera

Interventions

RuxolitinibDRUG

Ruxolitinib at a starting dose of 10mg, orally administered twice daily. If ruxolitinib is not tolerated, cross-over to the pegylated interferon α-2b alone group is allowed.

Pegylated interferon α-2bDRUG

Starting dose of 180ug, subcutaneous injection once a week. If complete hematological remission is not achieved after 12 weeks of treatment with pegylated interferon α-2b alone, cross-over to the pegylated interferon α-2b plus ruxolitinib group is allowed.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * ≥18 years old. * Male or Female. * Meets the diagnostic criteria for Polycythemia Vera according to WHO-2022. * Resistant or intolerant to hydroxyurea (based on the 2013 European LeukemiaNet criteria). * Have not previously received interferon preparations or ruxolitinib treatment, or the washout period between the last use of interferon preparations or ruxolitinib and the first use of the study drug should not be less than 4 weeks. * Patients with indications for cytoreductive therapy. * During screening, female hemoglobin (HGB) ≥10g/dL, male hemoglobin (HGB) ≥11g/dL; neutrophil count ≥1.5×109/L; platelet count ≥100×109/L. * Voluntary written informed consent. Exclusion Criteria: * Symptomatic splenomegaly; * Contraindications to interferon or ruxolitinib therapy; * Severe or significant comorbidities that may affect the participant's ability to participate in the study, as determined by the investigator; * History of major organ transplantation; * Pregnant or breastfeeding women; * History or current diagnosis of autoimmune thyroid disease (patients with controlled hypothyroidism on oral thyroid hormone replacement therapy may be included); * Documented evidence of any other autoimmune disease (such as active hepatitis, systemic lupus erythematosus, antiphospholipid antibody syndrome, or autoimmune arthritis); * Clinically significant bacterial, fungal, mycobacterial, parasitic, or viral infection such as active hepatitis or HIV infection (patients with acute bacterial infections requiring antibiotic treatment should be deferred from screening/enrollment until completion of antibiotic treatment); * Evidence of severe retinopathy or clinically significant ophthalmologic disease (due to diabetes or hypertension); * Current clinically significant depression or history of depression, or any suicidal attempt or tendency during screening; * Active bleeding or thrombotic complications; * History of any malignant tumor within the past 5 years (except for stage 0 chronic lymphocytic leukemia \[CLL\], cured basal cell carcinoma, squamous cell carcinoma, and superficial melanoma); * History of alcohol or substance abuse within the past year; * Presence of blasts in the peripheral blood within the past 3 months; * Use of any investigational drug or participation in any other clinical trial within 4 weeks prior to the first dose of the study drug, or failure to recover from any effects of previously administered study drugs; * The investigator deems the presence of any concurrent condition that may jeopardize the safety of the participant or the compliance to the protocol.

Locations (1)

Institute of Hematology & Blood Diseases Hospital

Tianjin, China

RECRUITING

Outcomes

Primary Outcomes

The cumulative complete hematologic response (CHR) rate

The proportion of patients who can achieve CHR ( defined as hematocrit lower than 45% without phlebotomies; platelet count \< 400×109/L, WBC count \< 10×109/L for at least 12 weeks) among all patients.

Time frame: From the start of study treatment (Week 0) up to the end of Week 24.

Secondary Outcomes

Cumulative CHR rates at Week 36.

Cumulative CHR rates at Week 36 will be compared between the two groups.

Time frame: From the start of study treatment (Week 0) up to the end of Week 36.

Cumulative CHR rates at Week 52.

Cumulative CHR rates at Week 52 will be compared between the two groups.

Time frame: From the start of study treatment (Week 0) up to the end of Week 52.

Time to CHR

The time of reaching CHR will be compared between the two groups.

Time frame: From the start of study treatment (Week 0) up to the end of Week 52.

The CHR rates after crossover

The CHR rates within 52 weeks after crossover

Time frame: From the start of study treatment (Week 0) up to the end of Week 52.

The rate of reduction in JAK2V617F, CALR, or MPL gene mutation burden.

The rate of reduction in JAK2V617F, CALR, or MPL gene mutation burden will be compared between the two groups.

Time frame: From the start of study treatment (Week 0) up to the end of Week 52.

Impact of therapy on non-driver mutations

To compare the proportion of subjects that display change on key non-driver biomarkers of the disease-DNMT3A, ASXL1, TET2 or other mutations.

Central Contacts

Lei Zhang, MD

CONTACT

8602223909240 zhanglei1@ihcams.ac.cn

Data from ClinicalTrials.gov

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