2024-511348-25-00进行中（未招募）2/3 期
A Study to Evaluate Imetelstat (GRN163L) in Transfusion-Dependent Subjects with IPSS Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS) that is Relapsed/Refractory to Erythropoiesis-Stimulating Agent (ESA) Treatment
干预措施
相关药物
试验速览
- 阶段
- 2/3 期
- 状态
- 进行中（未招募）
- 发起方
- Geron Corp.
- 入组人数
- 164
- 试验地点
- 37
- 主要终点
- The primary efficacy endpoint of this study is the rate of RBC TI lasting at least 8 weeks. The 8-week RBC TI rate is defined as the proportion of subjects without any RBC transfusion during any consecutive 8 weeks (56 days) starting from Study Day 1. Study Day 1 is defined as the day of the first dose for subjects enrolled in Part 1 and the day of randomization for subjects enrolled in Part 2.
研究概览
简要总结
Part 1: To evaluate the efficacy and safety of imetelstat in transfusion dependent subjects with low or intermediate-1 risk MDS that is relapsed/refractory to ESA treatment.
Part 2: To compare the efficacy, in terms of RBC TI, of imetelstat to placebo in transfusion dependent subjects with low or intermediate-1 risk MDS that is relapsed/refractory to ESA treatment.
Extension Phase: To evaluate the long-term safety, overall survival (OS), and disease progression, including progression to acute myeloid leukemia (AML) in transfusion dependent subjects with low or immediate-1 risk to MDS that is relapsed/refractory to ESA treatment receiving imetelstat.
研究设计
- 研究类型
- Interventional clinical trial of medicinal product
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
- •Man or woman ≥18 years of age (or the legal age of consent in the jurisdiction in which the study is taking place)
- •In Part 1, diagnosis of myelodysplastic syndromes (MDS) according to WHO criteria confirmed by bone marrow aspirate and biopsy within 12 weeks prior to C1D
- •A local laboratory report from this diagnostic bone marrow aspirate and biopsy must be reviewed and approved by the sponsor. In Part 2, diagnosis of MDS according to WHO criteria confirmed by bone marrow aspirate and biopsy within 12 weeks prior to Randomization. A sample of the baseline bone marrow aspirate and biopsy must be submitted to the Independent Central Pathology Reviewer for diagnostic confirmation. Central laboratory review is required to confirm diagnosis prior to Randomization.
- •International Prognostic Scoring System (IPSS) low or intermediate-1 risk MDS.
- •Red blood cell (RBC) transfusion dependent, defined as requiring at least 4 RBC units transfused over an 8-week period during the 16 weeks prior to C1D1 (Part 1) or Randomization (Part 2); pre-transfusion Hb should be ≤9.0 g/dL to count towards the 4 units total.
- •Has MDS that is relapsed/refractory to ESA treatment; as defined by meeting any one of the criteria below: - Received at least 8 weeks of treatment with a minimum weekly dose of epoetin alfa 40,000 U, epoetin beta 30,000 U or darbepoetin alfa 150 mcg (or equivalent agent/dose), without having achieved a Hb rise ≥1.5 g/dL or decreased RBC transfusion requirement by at least 4 units over 8 weeks - Transfusion dependence or reduction in Hb by ≥1.5 g/dL after hematologic improvement from at least 8 weeks of treatment with therapies outlined in the above inclusion criteria, in the absence of another explanation. - Endogenous serum EPO level >500 mU/mL
- •Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2.
排除标准
- •Subject has known allergies, hypersensitivity, or intolerance to imetelstat or its excipients.
- •Subject has received an experimental or investigational drug or used an invasive investigational medical device within 30 days prior to C1D1 (Part 1) or Randomization (Part 2) or is currently enrolled in an investigational study.
- •Prior treatment with imetelstat.
- •Have received corticosteroids >30 mg/day prednisone or equivalent, or growth factor treatment within 4 weeks prior to C1D1 (Part 1) or Randomization (Part 2).
- •a) Prior treatment with a hypomethylating agent (eg, azacitidine, decitabine); b) Prior treatment with lenalidomide, thalidomide, or other thalidomide analogues; c) Has received an ESA or any anti-MDS therapy, chemotherapy, immunomodulatory, or immunosuppressive therapy within 4 weeks prior to C1D1 (Part 1) or Randomization (Part 2) (8 weeks for long-acting ESAs).
研究组 & 干预措施
-
Auxiliary
Participants receiving -
干预措施: - (Drug)
结局指标
主要结局
The primary efficacy endpoint of this study is the rate of RBC TI lasting at least 8 weeks. The 8-week RBC TI rate is defined as the proportion of subjects without any RBC transfusion during any consecutive 8 weeks (56 days) starting from Study Day 1. Study Day 1 is defined as the day of the first dose for subjects enrolled in Part 1 and the day of randomization for subjects enrolled in Part 2.
The primary efficacy endpoint of this study is the rate of RBC TI lasting at least 8 weeks. The 8-week RBC TI rate is defined as the proportion of subjects without any RBC transfusion during any consecutive 8 weeks (56 days) starting from Study Day 1. Study Day 1 is defined as the day of the first dose for subjects enrolled in Part 1 and the day of randomization for subjects enrolled in Part 2.
次要结局
- Safety of imetelstat in subjects with MDS (eg, incidence, intensity, and type of adverse events, vital signs measurements, clinical laboratory values, ECGs changes, and deaths)
- 24-week RBC TI rate, defined as the proportion of subjects without any RBC transfusion during any consecutive 24 weeks (168 days) starting from Study Day 1
- Time to the 8-week (24 week) RBC TI, defined as the interval from Study Day 1 to the first day of the first 8-week (24 week) RBC TI period
- Duration of RBC TI, defined as the first day of the longest RBC TI period to the date of the first RBC transfusion after the TI period starts
- Rate of hematologic improvement, including HI-E, per modified IWG 2006
- Rates of CR, PR, or mCR per modified IWG 2006
- OS, defined as the interval from Study Day 1 to death from any cause. Survival time of living subjects will be censored on the last date a subject is known to be alive or lost to follow-up
- Progression free survival, defined as the time interval from Study Day 1 to the first date of disease progression or death from any cause, whichever occurs first. For subjects who do not have documented disease progression and who are still alive at the end of the study or clinical cutoff will be censored at the last disease evaluation date.
- Time to progression to AML, defined as the interval from Study Day 1 to the date of AML diagnosis. For subjects who have not progressed to AML and are still alive at the cutoff date for the analysis or who withdraw from the study (withdrawal of consent or lost to follow-up), data will be censored at the date of the last disease evaluation
- Amount and relative change in RBC transfusions
- Rate of myeloid growth factors usage, defined as the proportion of subjects receive any myeloid growth factors starting from Study Day 1; duration of myeloid growth factor administered starting from Study Day 1
- Assessment of QUALMS, FACT-An, and EQ-5D-5L
- Pharmacokinetic parameters (eg, Cmax, AUC0-t), and immunogenicity of imetelstat (eg, antibodies to imetelstat)
- Medical resource utilization data including hospitalization, emergency room visits, and hematology specialist visits
- ECG parameters including change in QT interval by Fridericia's correction method (ΔQTcF) in the Ventricular Repolarization substudy (Part 2 only)
研究者
Clinical Trial Enquiries
Scientific
Geron Corp.
研究点 (37)
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