An Open-Label, Single-Arm Phase II Study of Selinexor Monotherapy for Cytoreduction in Patients With BCR::ABL1-Negative Myeloproliferative Neoplasms
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 15
- 主要终点
- Proportion of Participants Achieving Disease-Relevant Peripheral Blood Count Control
研究概览
简要总结
Myeloproliferative neoplasms are chronic blood cancers in which the bone marrow produces too many blood cells. Patients with Philadelphia chromosome-negative myeloproliferative neoplasms, including polycythemia vera, essential thrombocythemia, and primary myelofibrosis, may need treatment to reduce high blood cell counts, relieve disease-related symptoms, and lower the risk of complications. However, currently available cytoreductive treatments may be ineffective, poorly tolerated, or inconvenient for some patients.
Selinexor is an oral selective inhibitor of nuclear export that has shown antitumor activity in several hematologic malignancies. This study will evaluate the effectiveness and safety of selinexor used alone as cytoreductive treatment in patients with Philadelphia chromosome-negative myeloproliferative neoplasms who have an indication for cytoreductive therapy.
This is a prospective, single-arm, open-label phase II study conducted at a single center. Eligible participants will receive oral selinexor, with dose adjustments based on tolerability and blood cell counts. Participants will be followed for treatment response, symptom improvement, and side effects for up to 6 months. The results of this study may help determine whether selinexor could provide a potential treatment option for patients with Philadelphia chromosome-negative myeloproliferative neoplasms who have limited cytoreductive therapy choices.
详细描述
This is a prospective, open-label, single-arm phase II study designed to evaluate the efficacy and safety of selinexor monotherapy as cytoreductive treatment in participants with Philadelphia chromosome-negative myeloproliferative neoplasms who have an indication for cytoreductive therapy.
Eligible participants will receive oral selinexor once weekly, starting at 40 mg. Dose escalation to 60 mg or 80 mg once weekly may be considered according to tolerability, hematologic response, and investigator judgment. Dose interruption or dose reduction will be permitted for hematologic or non-hematologic toxicities according to the protocol.
The primary objective is to evaluate the proportion of participants who achieve cytoreductive response based on disease-relevant peripheral blood count parameters, including platelet count, white blood cell count, and hematocrit where applicable. Secondary objectives include evaluation of symptom improvement, spleen-related response where applicable, safety, tolerability, and treatment discontinuation.
Participants will be followed for treatment response, adverse events, and overall clinical status for up to 6 months after treatment initiation. Safety assessments will include clinical evaluation, laboratory testing, and monitoring of treatment-emergent adverse events.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 18 to 80 years at the time of informed consent.
- •Diagnosis of Philadelphia chromosome-negative myeloproliferative neoplasm, including polycythemia vera, essential thrombocythemia, or primary myelofibrosis, according to World Health Organization criteria.
- •Presence of an indication for cytoreductive therapy, including at least one of the following:
- •Extreme thrombocytosis, defined as platelet count >1500 x 10^9/L.
- •Progressive leukocytosis, defined as white blood cell count >25 x 10^9/L.
- •Symptomatic splenomegaly documented by imaging.
- •Severe disease-related symptoms, such as significant weight loss within the past 6 months.
- •Unwillingness or inability to tolerate standard cytoreductive therapies, such as hydroxyurea or interferon.
- •Eastern Cooperative Oncology Group performance status of 0 to
- •Adequate organ function, including renal, hepatic, cardiac, and coagulation function, as determined by laboratory tests and clinical evaluation in the opinion of the investigator.
- •Adequate baseline hematologic function without recent transfusion or growth factor support.
- •Ability to comply with study procedures, visits, and assessments.
- •Ability to understand and willingness to sign a written informed consent form.
- •For women of childbearing potential, a negative pregnancy test before study entry.
- •For participants of reproductive potential, agreement to use effective contraception during the study and for at least 120 days after the last dose of study drug.
排除标准
- •Diagnosis of Philadelphia chromosome-positive myeloproliferative neoplasm or chronic myeloid leukemia.
- •Concurrent acute leukemia or other active hematologic malignancy.
- •Severe or uncontrolled comorbid condition, including but not limited to significant cardiac or pulmonary disease, decompensated liver disease, or end-stage renal disease.
- •Active uncontrolled bacterial, viral, or fungal infection.
- •Active gastrointestinal disorder associated with significant bleeding or impaired drug absorption.
- •Significant neurologic or psychiatric disorder that may interfere with study participation or compliance.
- •Known hypersensitivity to selinexor or any of its components.
- •Receipt of another investigational agent or participation in another interventional clinical trial within 4 weeks before enrollment.
- •Recent receipt of cytotoxic chemotherapy, radiotherapy, immunotherapy, or other cytoreductive treatment before study entry.
- •History of substance abuse, alcohol dependence, or illicit drug use that may interfere with adherence to study requirements.
- •Another active malignancy requiring systemic treatment.
- •Clinically significant bleeding disorder, severe coagulopathy, or requirement for long-term therapeutic anticoagulation.
- •Receipt of a live vaccine within 30 days before the first dose of study drug, or planned receipt of a live vaccine during the study.
- •Known active infection with human immunodeficiency virus or active viral hepatitis.
- •Estimated life expectancy of less than 12 weeks.
- •Inability to provide informed consent due to cognitive impairment or severe psychiatric illness.
- •Any condition that, in the investigator's judgment, would make the participant unsuitable for participation in this study.
研究组 & 干预措施
Selinexor Monotherapy
Participants in this arm will receive oral selinexor monotherapy as cytoreductive treatment. Selinexor will be administered once weekly, with dose adjustment based on safety, tolerability, and hematologic response.
干预措施: Selinexor (Drug)
结局指标
主要结局
Proportion of Participants Achieving Disease-Relevant Peripheral Blood Count Control
时间窗: Up to 6 months after initiation of study treatment
Disease-relevant peripheral blood count control will be assessed using hematologic parameters, including platelet count, white blood cell count, and hematocrit where applicable. A participant will be considered to have achieved cytoreductive response if the elevated disease-relevant blood count parameter at baseline normalizes or shows a clinically meaningful reduction from baseline according to the study protocol.
次要结局
- Proportion of Participants With Dose Interruption, Dose Reduction, or Treatment Discontinuation Due to Adverse Events(Up to 6 months after initiation of study treatment)
- Incidence of Treatment-Emergent Adverse Events(Up to 6 months after initiation of study treatment)
研究者
Zheng Wei, MD
Associate Chief Physician
Zhongshan Hospital (Xiamen), Fudan University