A Pilot Study of the Anti-SLAMF7 Monoclonal Antibody, Elotuzumab, in Patients With Myelofibrosis
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Overall response (OR)
研究概览
简要总结
This phase II trial investigates how well elotuzumab works in treating patients with JAK2-mutated myelofibrosis. Elotuzumab may help to control myelofibrosis and/or help to improve blood cell count and bone marrow function.
详细描述
PRIMARY OBJECTIVE:
I. To obtain preliminary evidence of the efficacy of elotuzumab in patients with myelofibrosis (MF) by estimating the rate of overall response by International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) 2013 criteria.
SECONDARY OBJECTIVES:
I. To characterize the safety and tolerability of elotuzumab in patients with MF.
II. To assess for improvements in cytopenias and bone marrow fibrosis grade, splenomegaly and disease-related symptoms.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults with JAK2 V617F+ primary myelofibrosis (PMF) or post-polycythemia vera (PV)/essential thrombocythemia myelofibrosis (ET-MF) who require treatment and have intermediate or higher risk disease (as assessed by the International Prognostic Scoring System for Myelodysplastic Syndrome [IPSS], Dynamic International Prognostic Scoring System [DIPSS], DIPSS-plus, Mutation-Enhanced Prognostic System for Transplant Age Patients with Primary Myelofibrosis [MIPSS70], MIPSS70-plus version [v] 2.0, or MYelofibrosis SECondary to PV and ET-Prognostic Model [MYSEC-PM]). The MYSEC-PM is to only be used for patients with post-PV/ET MF
- •Patients must not be candidates for JAK inhibitor therapy in the opinion of the treating physician
- •Bone marrow (BM) fibrosis grade 2 or 3 according to the European classification
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 (Karnofsky performance status >= 60%)
- •Absolute neutrophil count >= 0.5 x 10^9/L
- •Direct bilirubin =< 1.5 x institutional upper limit of normal
- •Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal unless felt to be due to liver involvement by MF/extramedullary hematopoiesis, in which case =< 5 x institutional upper limit of normal is permissible
- •Creatinine =< 2 x institutional upper limit of normal OR creatinine clearance >= 30 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
- •Ability to understand and the willingness to sign a written informed consent document
- •Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation until 6 months after the last administration of elotuzumab. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Women of child-bearing potential must have a negative pregnancy test. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after the last administration of elotuzumab
排除标准
- •Splenic irradiation within the preceding 4 months
- •Chemotherapy (other than hydroxyurea), interferons, IMiDs, danazol or other androgens, erythroid stimulating agents, or other MF-directed commercially available agents within 4 weeks prior to entering the study or those who have not recovered to baseline from adverse events due to agents administered more than 4 weeks earlier
- •Other investigational agents within 4 half-lives prior to study entry
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to elotuzumab
- •Patients with known central nervous system (CNS) involvement
- •Prior allogeneic hematopoietic cell transplantation (allo-HCT) for MF
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- •Known pregnancy or lactation
- •Known human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) positivity
研究组 & 干预措施
Treatment (elotuzumab)
Patients receive elotuzumab IV over 1-4 hours on days 1, 8, 15, and 22 of cycles 1-2. Beginning in cycle 3, patients receive elotuzumab IV over 1-4 hours on day 1. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Questionnaire Administration (Other)
Treatment (elotuzumab)
Patients receive elotuzumab IV over 1-4 hours on days 1, 8, 15, and 22 of cycles 1-2. Beginning in cycle 3, patients receive elotuzumab IV over 1-4 hours on day 1. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Elotuzumab (Biological)
结局指标
主要结局
Overall response (OR)
时间窗: Up to completion of cycle 36 (1 cycle is 28 days)
OR is defined as CR (complete response) +PR (partial response) + CI (clinical improvement), where CI includes clinical improvements in anemia, splenomegaly and/or symptoms. Will estimate the OR rate, along with the exact 95% confidence interval.
次要结局
- Time to next treatment(Up to 5 years)
- Duration of response(Up to 5 years)
- Changes in bone marrow fibrosis grade(Baseline up to 5 years)
- Rates of partial response(Up to 5 years)
- Rates of complete response(Up to 5 years)
- Rates of clinical improvement(Up to 5 years)
- Platelet response rate(Up to 5 years)
- Incidence of adverse events(Up to 30 days post-treatment)