CTRI/2021/11/037822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
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 320
- 试验地点
- 10
- 主要终点
- Overall survival
研究概览
简要总结
The purpose of the study is to evaluate the overall survival of participants treated with imetelstat compared to best available therapy with intermediate-2 or high-risk Myelofibrosis (MF) who are relapsed/refractory to Janus Kinase (JAK)-Inhibitor treatment
研究设计
- 研究类型
- Interventional
- 分配方式
- Stratified randomization
- 盲法
- Open Label
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •â€¢Diagnosis of primary myelofibrosis according to the revised World Health Organization criteria or post-essential thrombocythemia-MF or post-polycythemia vera-MF according to the IWG-MRT criteria •Dynamic International Prognostic Scoring System intermediate-2 or high-risk MF •Relapsed/Refractory to JAK-inhibitor treatment as defined in either inclusion (i) or (ii): (i) Treatment with JAK-inhibitor for greater than or equal to 6 months duration, including at least 2 months at an optimal dose as assessed by the investigator for that participant and one of the following: 1.no decrease in spleen volume (< 10% by MRI or CT) from the start of treatment with JAK-inhibitor 2.no decrease in spleen size (< 30% by palpation or length by imaging) from the start of treatment with JAK-inhibitor 3.no decrease in symptoms (< 20% by MFSAF or myeloproliferative neoplasm SAF) from the start of treatment with JAK-inhibitor) 4.a score of at least 15 on TSS assessed using the MFSAF v4.0 during screening. (ii) Treatment with JAK-inhibitor treatment for greater than or equal to 3 months duration with maximal doses (e.g., 20-25 mg twice daily ruxolitinib) for that participant and no decrease in spleen volume/size or symptoms as defined in inclusion criterion (i [a, b, or c]) (iii) 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 greater than 10 cm at the start of JAK inhibitor treatment, at least 50% increase in palpable spleen size from time of best response •Measurable splenomegaly demonstrated by a palpable spleen measuring greater than or equal to 5 cm below the left costal margin or a spleen volume greater than or equal to 450 cm 3 by MRI or CT •Active symptoms of MF on the MFSAF v4.0 demonstrated by a symptom score of at least 5 points (on a 0 to 10 scale) •Hematology laboratory test values within the protocol defined limits •Biochemical laboratory test values must be within protocol defined limits •Eastern Cooperative Oncology Group Performance Status score of 0, 1, or 2 •Participants should follow protocol defined contraceptives procedures •A woman of childbearing potential must have a negative serum or urine pregnancy test at screening.
排除标准
- •â€¢Peripheral blood blast count of greater than or equal to 10% or bone marrow blast count of greater than or equal to 10% •Known allergies, hypersensitivity, or intolerance to imetelstat or its excipients •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 greater than 30 mg/day prednisone or equivalent, and JAK-inhibitor treatment less than equal to 14 days prior to randomization •Diagnosis or treatment for malignancy other than MF except 1.Malignancy treated with curative intent and with no known active disease present for greater than or equal to 3 years before randomization 2.Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease 3.Adequately treated cervical carcinoma in situ without evidence of disease •Known history of human immunodeficiency virus or any uncontrolled active systemic infection requiring IV antibiotics •Active systemic hepatitis infection requiring treatment (carriers of hepatitis virus are permitted to enter the study), or any known acute or chronic liver disease unless related to underlying hepatosplenomegaly due to MF •Major surgery within 28 days prior to randomization •Any life-threatening illness (e.g. coronavirus disease-2019) medical condition, or organ system dysfunction which, in the investigators opinion, could compromise the participants safety, interfere with the imetelstat metabolism, or put the study outcomes at undue risk.
结局指标
主要结局
Overall survival
时间窗: Baseline (Day 1) until End of Study (EOS) (approximately 3 years)
次要结局
- Symptom response rate(Baseline (Day 1), and at Week 24)
- Progression-free survival(Baseline (Day 1) until End of Study (EOS) (approximately 3 years))
- Spleen response rate(Baseline (Day 1), and at Week 24)
- Complete remission (CR), partial remission (PR), clinical improvement (CI), spleen response, symptoms response, and anemia response per modified 2013 IWG-MRT criteria(Baseline (Day 1) until End of Treatment (approximately 3 years))
- Reduction in the degree of bone marrow fibrosis(Baseline (Day 1) until End of Treatment (approximately 3 years))
- Number of Participants with Adverse Events(Screening (Day -28 to -1) until End of Study (approximately 3 years))
- Assessment of Cmax(Day 1 of all cycles (each cycle is 21 days))
- European Organization for Research and Treatment of Cancer Quality-of-Life-Questionnaire-Core-30 (EORTC QLQ-C30) scores(Baseline to End of Study (approximately 3 years))
- EuroQol-EQ-5D (EQ-5D-5L) questionnaire scores(Baseline to End of Study (approximately 3 years))
- Assessment of AUC(Day 1 of all cycles (each cycle is 21 days))
研究者
研究点 (10)
Loading locations...
相似试验
进行中（未招募）
3 期
A Study Comparing Imetelstat Versus Best Available Therapy for the Treatment of Intermediate-2 or High-risk Myelofibrosis (MF) Who Have Not Responded to Janus Kinase (JAK)-Inhibitor TreatmentMyelofibrosisNCT04576156Geron Corporation327
招募中
3 期
A study comparing current available therapies with imetelstat for the treatment of intermediate-2 or high-risk MF who are not responding to JAK-inhibitor treatmentMyelofibrosis2023-509120-17-00Geron Corp.260
已完成
3 期
A Multinational, Randomized, Open-Label Study of Custirsen In Patients With Advanced or Metastatic (Stage IV) Non-Small Cell Lung CancerNon-Small Cell Lung CancerNCT01630733Achieve Life Sciences664
已完成
3 期
A Study to Evaluate Enfortumab Vedotin Versus (vs) Chemotherapy in Subjects With Previously Treated Locally Advanced or Metastatic Urothelial Cancer (EV-301)Ureteral CancerUrothelial CancerBladder CancerNCT03474107Astellas Pharma Global Development, Inc.608
已完成
3 期
Study of C1 Inhibitor (Human) for the Prevention of Angioedema Attacks and Treatment of Breakthrough Attacks in Japanese Subjects With Hereditary Angioedema (HAE)Hereditary Angioedema (HAE)NCT02865720Shire8