Study of Pelabresib add-on to Ruxolitinib in Japanese Adult Patients With Myelofibrosis
Ориентир для пациента и семьи
Простыми словами
Автоматическая сводка по структурированным данным реестра. Она помогает сориентироваться, но не заменяет официальный протокол или оценку врача.
- Что изучают
- В протоколе указаны: Pelabresib, Ruxolitinib.
- Кому может быть актуально
- Состояния в реестре: Primary Myelofibrosis (PMF), Post-polycythemia Vera Myelofibrosis (Post-PV MF), Post-essential Thrombocythemia Myelofibrosis (Post-ET MF). Базовые параметры: от 18 лет · Все.
- Что важно проверить
- Возраст, диагноз и пол — только базовые ориентиры. Предыдущее лечение, анализы и другие обязательные условия указаны ниже в критериях участия.
- Где проводится
- Япония
- Следующий шаг
- Сохраните исследование, покажите его лечащему врачу и уточните актуальный статус у исследовательского центра. Расходы, документы и поездка →
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Официальное название
A Phase 1b Study of Pelabresib (DAK539) add-on to Stable Dose of Ruxolitinib in Japanese Adult Patients With Myelofibrosis
Обзор
This Phase 1b, multicenter, open-label study aims to evaluate the safety, pharmacokinetics (PK), and preliminary efficacy of pelabresib as add-on to ruxolitinib in Japanese patients with myelofibrosis (MF).
Подробное описание
This study consists of three periods: screening, treatment, and follow-up. After a screening period of up to 28 days, between three and nine eligible and evaluable participants will be enrolled to receive pelabresib in addition to a stable dose of ruxolitinib.
The follow-up phase includes a 30-day safety follow-up and a long-term follow-up. Pelabresib will be administered until one of the following occurs: disease progression, unacceptable toxicity, death, participant decision, or investigator decision.
After discontinuation of pelabresib, safety assessments will continue with a safety follow-up visit 30 days after the last dose of pelabresib. Participants will then be contacted for long-term follow-up approximately every 12 weeks after the end of treatment (EOT) for at least three years from the first dose of pelabresib and for at least two years following the last dose of pelabresib, whichever is longer. Long-term follow-up will continue until death, withdrawal from the study, loss to follow-up, or completion of the follow-up period, whichever occurs first.
Safety follow-up and long-term follow-up visits will include assessment for leukemic transformation, which will be conducted throughout the study and for up to two years after treatment. The study will continue until all participants complete long-term follow-up or until access to pelabresib is ensured through a post-trial access program or reimbursement of pelabresib in Japan becomes available.
Japanese safety confirmation will be determined according to the decision rule. The starting dose is 125 milligrams once daily (QD), and no dose escalation or de-escalation for safety confirmation is planned in this study. Initially, three participants will receive 125 milligrams QD of pelabresib as an add-on to ruxolitinib. The dose-limiting toxicity (DLT) evaluation period for Japanese safety confirmation is 21 days (one cycle).
Вмешательства
- Препарат Pelabresib
125 mg orally once daily (QD) on Days 1-14 of each 21-day cycle - Препарат Ruxolitinib
5-25 mg twice daily (BID)
Первичные конечные точки
- Incidence of dose-limiting toxicities (DLTs) [Срок оценки: Up to 21 days]
- Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) [Срок оценки: Through study completion, an average of approximately 4 years]
Вторичные конечные точки (6)
- Plasma concentration time profiles of pelabresib [Срок оценки: Cycle 1: Days 1/14 (0/Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours post-dose), Days 2/15 (0/Pre-dose (immediately before the next pelabresib administration)). 1 cycle = 21 days.]
- Area Under the plasma concentration-time Curve (AUC) of pelabresib [Срок оценки: Cycle 1: Days 1/14 (0/Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours post-dose), Days 2/15 (0/Pre-dose (immediately before the next pelabresib administration)). 1 cycle = 21 days.]
- Maximum observed plasma Concentration (Cmax) of pelabresib [Срок оценки: Cycle 1: Days 1/14 (0/Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours post-dose), Days 2/15 (0/Pre-dose (immediately before the next pelabresib administration)). 1 cycle = 21 days.]
- Time to Maximum observed plasma Concentration (Tmax) of pelabresib [Срок оценки: Cycle 1: Days 1/14 (0/Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours post-dose), Days 2/15 (0/Pre-dose (immediately before the next pelabresib administration)). 1 cycle = 21 days.]
- Absolute change from baseline and percentage change from baseline in spleen volume over time (Week 24 and 48), as measured by MRI (or CT scan). [Срок оценки: Baseline, Week 24, Week 48]
- Absolute change from baseline and percentage change from baseline in Total Symptom Score (TSS) over time (until Week 48), as measured by the Myelofibrosis Symptom Assessment Form (MFSAF) v4.0 [Срок оценки: Baseline and up to Week 48]
Критерии участия
Критерии включения
- Participants have diagnosis of primary myelofibrosis (PMF), post-polycythemia vera MF (Post-PV MF) or post-essential thrombocythemia MF (Post-ET MF) according to the International Consensus Classification (ICC) for Myeloid Neoplasms and Acute Leukemias 2022.
- DIPSS risk category intermediate-1, intermediate-2 or high-risk at screening.
- Participants currently treated with ruxolitinib monotherapy AND who are likely to benefit from the addition of pelabresib to ruxolitinib in the opinion of the investigator.
- Receiving ruxolitinib at a stable dose (5 to 25 mg BID) for at least 8 weeks prior to the first dose of pelabresib.
- Palpable spleen (spleen length below left costal margin \[LCM\] must be recorded) or documented splenomegaly by MRI or CT (image report must be recorded) at screening.
- Platelet count ≥ 100 × 10\^9/L in the absence of growth factor support (including thrombopoietin mimetics/agonists) or platelet transfusions 4 weeks prior to the first dose of pelabresib.
- Blasts < 5% in peripheral blood. Assessment of blasts in peripheral blood is mandatory at screening.
Критерии исключения
- Prior splenectomy at any time or splenic irradiation in the previous 6 months
- Prior hematopoietic cell transplant or participants anticipated to receive a hematopoietic cell transplant within 24 weeks from the first dose of pelabresib.
- Blasts ≥ 5% in bone marrow if results available at screening or history of accelerated phase or leukemic transformation.
- History of a malignancy (other than MF, PV or ET) except for adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy or requiring only hormonal therapy and with normal prostate-specific antigen for ≥ 1 year prior to start of pelabresib, adequately treated Stage 1 or 2 cancer currently in complete remission, or any other cancer that has been in complete remission for ≥ 3 years
- Received any approved or investigational agent for the treatment of MF except ruxolitinib within 14 days of first dose of pelabresib or within 5 half-lives of the approved or investigational agent, whichever is longer.
Other protocol-defined inclusion/exclusion criteria may apply.
Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.
Здоровые добровольцы: Нет
Дизайн исследования
- Распределение
- Не применимо
- Модель
- Одна группа
- Маскирование
- Открытое
- Основная цель
- Лечение
Центры проведения
Япония · 7 центров
- Novartis Investigative Site — Kamogawa
- Novartis Investigative Site — Sapporo
- Novartis Investigative Site — Kamakura
- Novartis Investigative Site — Kurashiki
- Novartis Investigative Site — Bunkyo Ku
- Novartis Investigative Site — Chūō
- Novartis Investigative Site — Kumamoto
Идентификаторы
NCT: NCT07340138 · CDAK539A11101