Clinical trial NCT05870475: Pegylated Interferon α-2b in Combination With Ruxolitinib for Treating Hydroxyurea-resistant/Intolerant PV
Official title: A Randomized Controlled Study Evaluating the Efficacy and Safety of Pegylated Interferon α-2b in Combination With Ruxolitinib vs. Pegylated Interferon α-2b Monotherapy for Treating Hydroxyurea-resistant/Intolerant Polycythemia Vera
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Polycythemia Vera
Lead sponsor: Institute of Hematology & Blood Diseases Hospital, China
Sponsor class: OTHER
First posted: 2023-05-23
Enrollment: 94
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: The cumulative complete hematologic response (CHR) rate
timeFrame: From the start of study treatment (Week 0) up to the end of Week 24.
Secondary outcomes:
measure: Cumulative CHR rates at Week 36.
timeFrame: From the start of study treatment (Week 0) up to the end of Week 36.
measure: Cumulative CHR rates at Week 52.
timeFrame: From the start of study treatment (Week 0) up to the end of Week 52.
measure: Time to CHR
timeFrame: From the start of study treatment (Week 0) up to the end of Week 52.
measure: The CHR rates after crossover
timeFrame: From the start of study treatment (Week 0) up to the end of Week 52.
measure: The rate of reduction in JAK2V617F, CALR, or MPL gene mutation burden.
timeFrame: From the start of study treatment (Week 0) up to the end of Week 52.
measure: Impact of therapy on non-driver mutations
timeFrame: From the start of study treatment (Week 0) up to the end of Week 52.
measure: Change of splenomegaly
timeFrame: From the start of study treatment (Week 0) up to the end of Week 52.]
measure: Change of bone marrow pathology
timeFrame: From the start of study treatment (Week 0) up to the end of Week 52
measure: The incidence of major thrombotic events
timeFrame: From the start of study treatment (Week 0) up to the end of Week 52.
measure: The incidence of major bleeding events
timeFrame: From the start of study treatment (Week 0) up to the end of Week 52.
measure: The incidence of progressing to acute leukemia
timeFrame: From the start of study treatment (Week 0) up to the end of Week 52.
measure: Change in Myeloproliferative Neoplasm Symptom Assessment Form total symptom score
timeFrame: From the start of study treatment (Week 0) up to the end of Week 52.
measure: Change of quality of life using QLQ-C30 V3.0 questionnaire.
timeFrame: From the start of study treatment (Week 0) up to the end of Week 52.
measure: Change of microcirculation disturbance
timeFrame: From the start of study treatment (Week 0) up to the end of Week 52.
measure: Specific pre-defined toxicity
timeFrame: From the start of study treatment (Week 0) up to the end of Week 52.
Other outcomes:
measure: Changes of T lymphocytes
timeFrame: From the start of study treatment (Week 0) up to the end of Week 52.
measure: Changes of B lymphocytes
timeFrame: From the start of study treatment (Week 0) up to the end of Week 52.
measure: Changes of dendritic cells
timeFrame: From the start of study treatment (Week 0) up to the end of Week 52.
Locations:
city: Tianjin
country: China
facility: Institute of Hematology & Blood Diseases Hospital
Study officials:
affiliation: Institute of Hematology & Blood Diseases Hospital, China
name: Lei Zhang, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Institute of Hematology & Blood Diseases Hospital, China
name: Rongfeng Fu
role: PRINCIPAL_INVESTIGATOR
References: