Phase II Study of Reparixin in Patients With Myelofibrosis Myeloproliferative Neoplasms Research Consortium [MPN-RC 120]
概览
- 阶段
- 2 期
- 干预措施
- reparixin
- 疾病 / 适应症
- Myelofibrosis (PMF)
- 发起方
- Icahn School of Medicine at Mount Sinai
- 入组人数
- 26
- 试验地点
- 16
- 主要终点
- Efficacy of reparixin treatment per IWG/ELN criteria
- 状态
- 招募中
- 最后更新
- 3个月前
概览
简要总结
This is an open label, phase II study to assess the efficacy, safety, and tolerability of Reparixin in patients with DIPSS intermediate-2, or high-risk primary myelofibrosis (PMF), post essential thrombocythemia/polycythemia vera related MF (Post ET/PV MF) after prior treatment, and those who are ineligible or refuse treatment, with a Janus kinase inhibitor (JAKi). 26 patients will be enrolled. Eligible patients will receive oral reparixin three times daily on a 4-week cycle for a core study period of 6 cycles (24 weeks). After cycle 6, patients may continue receiving reparixin once daily on a 4-week cycle if at least stable disease (SD) is met by IWG-MRT criteria until loss of response, disease progression, unacceptable toxicity, patient/physician withdrawal, or termination of study by sponsor.
研究者
Marina Kremyanskaya
Associate Professor
Icahn School of Medicine at Mount Sinai
入排标准
入选标准
- •Be ≥ 18 years of age at time of signing the informed consent form (ICF)
- •Willing to voluntarily sign the ICF
- •Have a pathologically confirmed diagnosis of PMF, post-ET-MF, or post-PV-MF as per the World Health Organization (WHO) diagnostic criteria with intermediate-2 or higher risk disease by DIPSS
- •Have an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- •Willing to undergo a bone marrow biopsy at screening
- •o A bone marrow biopsy obtained within 90 days of screening without intervening treatments and approved by the study chair may suffice.
- •Be refractory/resistant to or intolerant of/inappropriate for JAKi therapy as defined by at least one of the following:
- •Treatment for ≥ 3 months with inadequate efficacy as demonstrated by persistent palpable splenomegaly ≥ 5cm or symptoms related to splenomegaly,
- •Treatment for ≥ 28 days complicated by either:
- •Development of a red blood cell transfusion requirement (at least 2 units/month for 2 months)
排除标准
- •History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within the last 6 months
- •Other invasive malignancies within the last 3 years, except non-melanoma skin cancer and localized cured prostate and cervical cancer
- •Moderate or severe cardiovascular disease meeting one or both of the below criteria:
- •Presence of cardiac disease, including a myocardial infarction within 6 months prior to study entry, unstable angina pectoris, New York Heart Association Class III/IV congestive heart failure, or uncontrolled hypertension
- •Documented major electrocardiogram (ECG) abnormalities (not responding to medical treatments)
- •Presence of active serious infection
- •Any serious, unstable medical or psychiatric condition that would prevent (as judged by the Investigator) the participant from signing the ICF or any condition, including the presence of laboratory abnormalities, which places the participant at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
- •Participants who have undergone a hematopoietic cell transplant (HCT) within 100 days of the first dose of study therapy, participants on immunosuppressive therapy post-HCT at screening, use of calcineurin inhibitors within 4 weeks prior to first dose of study therapy, or participants with clinically significant graft-versus-host disease (GVHD)
- •o Note: The use of topical steroids or \< 10mg oral prednisone for ongoing skin GVHD is permitted
- •Known history of human immunodeficiency virus (HIV), or known active hepatitis A, B, or C infection
研究组 & 干预措施
Reparixin
Eligible patients will receive oral reparixin three times daily on a 4-week cycle for a core study period of 6 cycles (24 weeks). After cycle 6, patients may continue receiving reparixin once daily on a 4-week cycle if at least stable disease (SD) is met by IWG-MRT criteria until loss of response, disease progression, unacceptable toxicity, patient/physician withdrawal, or termination of study by sponsor.
干预措施: reparixin
结局指标
主要结局
Efficacy of reparixin treatment per IWG/ELN criteria
时间窗: Cycle 6 (each cycle is 4 weeks) Response Assessment
To estimate the efficacy of reparixin treatment in DIPSS intermediate-2 or high-risk subjects with PMF, post PV-MF, or post ET-MF as assessed by IWG/ELN criteria. The IWG/ELN criteria: CR (complete remission), PR (partial remission), Clinical improvement, Anemia response, Spleen response, Symptoms response, PD (progressive disease), SD (stable disease), Relapse, Cytogenetic remission, and Molecular remission
次要结局
- Change in Spleen Volume(Baseline and cycle 12 (each cycle is 4 weeks))
- Response Assessment of IWG/ELN(end of Cycle 12 (each cycle is 4 weeks))
- Bone marrow fibrosis grade(end of Cycle 12 (each cycle is 4 weeks))
- Number of Adverse Events(End of study (24 weeks) plus 3 months)
- Response Assessment of IWG/ELN(end of Cycle 6 (each cycle is 4 weeks))
- Bone marrow fibrosis grade(end of Cycle 6 (each cycle is 4 weeks))
- Change in Spleen Volume(Baseline and cycle 6 (each cycle is 4 weeks))