Study to Evaluate Imetelstat (GRN163L) in Subjects With International Prognostic Scoring System (IPSS) Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS)

ID#: NCT02598661

Age: 18 years - 66+

Gender: All

Healthy Subjects: No

Study Phase: Phase 2/Phase 3

Recruitment Status: Recruiting

Start Date: November 24, 2015

End Date: October 13, 2023

Contact Information:
Faye Feller, MD
Souria Dougherty
Summary: The purpose of this study is to evaluate the efficacy and safety of imetelstat in transfusion-dependent participants with low or intermediate-1 risk myelodysplastic syndrome (MDS) that is relapsed/refractory to erythropoiesis-stimulating agent (ESA) treatment in Part 1 of the study and to compare the efficacy, in terms of red blood cell (RBC) transfusion independence (TI), of imetelstat to placebo in transfusion-dependent participants with low or intermediate-1 risk MDS that is relapsed/refractory to ESA treatment in Part 2 of the study. An Extension Phase has been included to allow continued treatment for those subjects who are benefitting from imetelstat and to continue to evaluate the long-term safety, overall survival (OS), and disease progression, including progression to acute myeloid leukemia (AML) in transfusion-dependent participants with low or immediate-1 risk MDS that is relapsed/refractory to ESA treatment.

Inclusion Criteria:

- Man or woman greater than or equal to (>=) 18 years of age

- Diagnosis of myelodysplastic syndrome (MDS) according to World Health Organization (WHO) criteria confirmed by bone marrow aspirate and biopsy within 12 weeks prior to Cycle 1 Day 1 (C1D1) (Part 1) or randomization [Part 2 (Main Study)]. In Part 2 (Ventricular Repolarization Substudy), diagnosis of MDS or myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T) according to WHO criteria confirmed by bone marrow aspirate and biopsy within 12 weeks prior to C1D1

- International Prognostic Scoring System (IPSS) low Risk 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 Study Entry; pre-transfusion hemoglobin (Hb) should be less than or equal to 9.0 gram per deciliter (g/dL) to count towards the 4 units total

- Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2

Exclusion Criteria:

- Participant has known allergies, hypersensitivity, or intolerance to imetelstat or its excipients

- Participant has received an investigational drug or used an invasive investigational medical device within 30 days prior to Study Entry or is currently enrolled in an investigational study

- Prior treatment with imetelstat

- Have received corticosteroids greater than (>) 30 milligram per day (mg/day) prednisone or equivalent, or growth factor treatment within 4 weeks prior to study entry

- Has received an erythropoiesis-stimulating agent (ESA) or any chemotherapy, immunomodulatory, or immunosuppressive therapy within 4 weeks prior to study entry (8 weeks for long-acting ESAs)

- Part 2 (Main Study): a) Prior treatment with a hypomethylating agent (example [eg], azacitidine, decitabine); b) Prior treatment with lenalidomide Additional Exclusion Criteria for Part 2 (Ventricular Repolarization Substudy)

- Concurrent therapy with medications known to prolong the QT interval and have been associated with Torsade de pointes arrhythmia (TdP)

- Cardiac function abnormalities on screening ECG as follows:

- Resting heart rate outside of 50 to 100 beats per minute

- QTcF >470 millisecond (msec) (or QTcF >490 msec in the presence of a right bundle branch block or ventricular conduction delay [QRS >119 msec]), determined by central assessment based on the average value of a triplicate set of ECGs

- Diagnosed or suspected congenital long QT syndrome

- Family history of sudden unexpected death from cardiac-related causes if indicative of a pathogenic mutation of cardiac ion channels

- Family history of congenital long QT syndrome

- History of Mobitz II second degree or third degree heart block

- Implantable pacemaker or automatic implantable cardioverter defibrillator

- Complete left bundle branch block

- Chronic or persistent atrial arrhythmia including atrial fibrillation and atrial flutter

- History or presence of clinically relevant heart rhythm disturbances including atrial, junctional, re-entry, and ventricular tachycardia

- Unusual T-wave morphology (i.e., bifid T-wave) likely to interfere with QT measurements

- History or evidence for any of the following: severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (example, pulmonary embolism, cerebrovascular accident including transient ischemic attacks) within 12 months prior to Cycle 1 Day 1, New York Heart Association (NYHA) Class II to IV heart disease

- Presence of uncontrolled hypertension (persistent systolic blood pressure [BP] ≥160 mmHg or diastolic BP ≥100 mmHg). Participants with a history of hypertension are permitted, provided that BP is controlled to within these limits by anti-hypertensive treatment

- Any skin condition likely to interfere with electrocardiographic electrode placement or adhesion

- History of thoracic surgery likely to cause abnormality of the electrical conduction through thoracic tissues