2023-509120-17-00招募中3 期
A Randomized Open-Label, Phase 3 Study to Evaluate Imetelstat (GRN163L) Versus Best Available Therapy (BAT) in Patients with Intermediate-2 or High-risk Myelofibrosis (MF) Relapsed / Refractory (R/R) to Janus Kinase (JAK)-Inhibitor
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- Geron Corp.
- 入组人数
- 260
- 试验地点
- 80
- 主要终点
- Overall survival (OS), defined as the time interval from randomization date to date of death from any cause.
研究概览
简要总结
The primary objective of this study is to compare the overall survival (OS) of participants, treated with imetelstat versus BAT, with intermediate-2 or high-risk Myelofibrosis (MF) whose disease is relapsed / refractory to JAK-inhibitor treatment.
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •Diagnosis of PMF according to the revised WHO criteria (Section 18.2); or PET-MF or PPV-MF according to the IWG-MRT criteria (Section 18.3) confirmed by local pathology report.
- •Dynamic International Prognostic Scoring System intermediate-2 or high-risk MF (Section 18.4).
- •Relapsed / Refractory to JAK-inhibitor treatment as defined in either inclusion 4.1, 4.2 or 4.3 and not eligible for ASCT at screening: 4.1: Treatment with JAK-inhibitor for ≥ 6 months duration, including at least 2 months at an optimal dose as assessed by the investigator for that participant and at least ONE of the following: a) no decrease in spleen volume (< 10% by MRI or CT) from the start of treatment with JAK-inhibitor. b) no decrease in spleen size (< 30% by palpation or length by imaging) from start of treatment with JAK-inhibitor. c) no decrease in symptoms (< 20% by MFSAF or myeloproliferative neoplasm SAF) from start of treatment with JAK-inhibitor. d) a score of at least 15 on TSS assessed using the MFSAF v4.0 (adapted as the MF Symptom Recall Form, Section 18.6) during screening. 4.2: Treatment with JAK-inhibitor for ≥ 3 months duration with maximal doses for that participant (e.g. 20-25 mg twice daily ruxolitinib) without a spleen or symptom response as defined in inclusion criterion 4.1 (a, b, or c) and would not benefit from remaining on treatment for 6 months. 4.3: Following maximum tolerated doses of JAK inhibitor therapy for ≥3 months duration, having documented relapsed disease defined as either: • Increase in spleen volume from time of best response by 25% measured by MRI or CT, or • Increase in spleen size by palpation, CT, or ultrasound - For splenomegaly of 5-10 cm at the start of JAK inhibitor treatment, at least 100% increase in palpable spleen size from time of best response; - For splenomegaly of > 10 cm at the start of JAK inhibitor treatment, at least 50% increase in palpable spleen size from time of best response; AND not a candidate for further JAK inhibitor at screening per investigator.
- •Measurable splenomegaly demonstrated by a palpable spleen measuring ≥ 5 cm below the left costal margin or a spleen volume ≥ 450 cm3 by MRI or CT.
- •Active symptoms of MF on the MFSAF v4.0 (adapted as the MF Symptom Recall Form, Section 18.6) demonstrated by a symptom score of at least 5 points (on a 0 to 10 scale) on at least 1 of the symptoms or a score of 3 or greater on at least 2 of the following symptoms: fatigue, night sweats, itchiness, abdominal discomfort, pain under ribs on left side, early satiety, and bone pain.
- •Hematology laboratory test values within the following limits: • absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L independent of growth factor support, AND • platelets ≥ 75 x 10^9/L independent of platelet transfusion support.
排除标准
- •Peripheral blood blast count of ≥ 10% or bone marrow blast count of ≥ 10%.
- •Prior treatment with imetelstat.
- •Any chemotherapy or MF directed therapy, including investigational drug regardless of class or mechanism of action, immunomodulatory or immunosuppressive therapy, corticosteroids > 30 mg/day prednisone or equivalent, and JAK-inhibitor treatment ≤ 14 days prior to randomization.
- •Diagnosis or treatment for malignancy other than MF except: - Malignancy treated with curative intent and with no known active disease present for ≥ 3 years before randomization. - Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. - Adequately treated cervical carcinoma in situ without evidence of disease.
- •Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification.
- •Known history of human immunodeficiency virus or any uncontrolled active systemic infection requiring IV antibiotics.
研究组 & 干预措施
-
Active Comparator
Participants receiving -
干预措施: - (Drug)
结局指标
主要结局
Overall survival (OS), defined as the time interval from randomization date to date of death from any cause.
Overall survival (OS), defined as the time interval from randomization date to date of death from any cause.
次要结局
- Symptom response rate at Week 24 (defined as the proportion of patients who have ≥ 50% reduction in TSS at Week 24 from baseline as measured by the MFSAF v4.0)
- Progression-Free Survival, defined as the time interval from randomization date to the first date of disease progression (worsening splenomegaly or leukemic transformation per 2013 IWG-MRT criteria) or death from any cause, whichever occurs first.
- Spleen response rate at Week 24 (defined as the proportion of patients who achieve ≥ 35% reduction in spleen volume at Week 24 from baseline as measured by imaging scans). For additional secondary end points please refer to the study protocol.
研究者
Clinical Trial Enquiries
Scientific
Geron Corp.
研究点 (80)
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