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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Ruxolitinib
  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.
• Препарат Pegylated interferon α-2b
  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.

Первичные конечные точки

• The cumulative complete hematologic response (CHR) rate [Срок оценки: From the start of study treatment (Week 0) up to the end of Week 24.]

Вторичные конечные точки (12)

• Cumulative CHR rates at Week 36. [Срок оценки: From the start of study treatment (Week 0) up to the end of Week 36.]
• Cumulative CHR rates at Week 52. [Срок оценки: From the start of study treatment (Week 0) up to the end of Week 52.]
• Time to CHR [Срок оценки: From the start of study treatment (Week 0) up to the end of Week 52.]
• The CHR rates after crossover [Срок оценки: 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. [Срок оценки: From the start of study treatment (Week 0) up to the end of Week 52.]
• Impact of therapy on non-driver mutations [Срок оценки: From the start of study treatment (Week 0) up to the end of Week 52.]
• Change of splenomegaly [Срок оценки: From the start of study treatment (Week 0) up to the end of Week 52.]]
• Change of bone marrow pathology [Срок оценки: From the start of study treatment (Week 0) up to the end of Week 52]
• The incidence of major thrombotic events [Срок оценки: From the start of study treatment (Week 0) up to the end of Week 52.]
• The incidence of major bleeding events [Срок оценки: From the start of study treatment (Week 0) up to the end of Week 52.]
• The incidence of progressing to acute leukemia [Срок оценки: From the start of study treatment (Week 0) up to the end of Week 52.]
• Change in Myeloproliferative Neoplasm Symptom Assessment Form total symptom score [Срок оценки: From the start of study treatment (Week 0) up to the end of Week 52.]

Критерии участия

Критерии включения

• ≥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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Institute of Hematology & Blood Diseases Hospital — Тяньцзинь

Идентификаторы

NCT: NCT05870475 · IIT2023018

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗