Study to Evaluate Imetelstat (GRN163L) in Participants With International Prognostic Scoring System (IPSS) Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS)
Placebo: Imetelstat sodium-matching placebo IV infusion.
Study summary
The purpose of this study is to evaluate the efficacy and safety of imetelstat sodium in transfusion-dependent participants with low or intermediate-1 risk myelodysplastic syndrome (MDS) that is relapsed/refractory to erythropoiesis-stimulating agent (ESA) treatment in Phase 2 study and to compare the efficacy, in terms of red blood cell (RBC) transfusion independence (TI), of imetelstat sodium to placebo in transfusion-dependent participants with low or intermediate-1 risk MDS that is relapsed/refractory to ESA treatment in Phase 3 study.
A separate Ventricular Repolarization Substudy (QTc Substudy) will evaluate the effect of imetelstat sodium on ventricular repolarization.
An Extension Phase has been included to allow continued treatment for those participants who are benefitting from imetelstat sodium 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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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) (Phase 2) or randomization (Phase 3). In 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 sodium 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 sodium
* 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)
* Phase 3: a) Prior treatment with a hypomethylating agent (example \[eg\], azacitidine, decitabine); b) Prior treatment with lenalidomide
Additional Exclusion Criteria for the 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
* QT interval by Fridericia's correction method (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
Primary outcome measure(s)
Phase 2: Percentage of Participants Without Any Red Blood Cell (RBC) Transfusion During Any Consecutive 8-Weeks Period (All Participants) — Up to 5 years in Phase 2 Percentage of participants without any RBC transfusion during any consecutive 8 weeks (56 days) starting from Study Day 1 until subsequent anti-cancer therapy if any were reported. Study Day 1 is defined as the day of the first dose for participants enrolled in Phase 2. The 95% confidence interval (CI) was calculated using Clopper-Pearson method. Percentages were rounded off to the nearest single decimal place.
Phase 2: Percentage of Participants Without Any RBC Transfusion During Any Consecutive 8-Weeks Period in Target Population — Up to 5 years in Phase 2 Percentage of participants without any RBC transfusion during any consecutive 8 weeks (56 days) starting from Study Day 1 until subsequent anti-cancer therapy if any were reported. Study Day 1 is defined as the day of the first dose for participants enrolled in Phase 2. The 95% confidence interval (CI) was calculated using Clopper-Pearson method. Percentages were rounded off to the nearest single decimal place.
Phase 3: Percentage of Participants Without Any RBC Transfusion During Any Consecutive 8-Weeks Period — Up to 3.7 years in Phase 3 Percentage of participants without any RBC transfusion during any consecutive 8 weeks (56 days) starting from Study Day 1 until subsequent anti-cancer therapy if any were reported. Study Day 1 is defined as the day of the first dose for participants enrolled in Phase 2. The 95% CI was calculated using Clopper-Pearson method. Percentages were rounded off to the nearest single decimal place.
Trial sites (126)
Facility
City
Region
Status
UAB Comprehensive Cancer Center
Birmingham
Alabama
Acrc/Arizona Clinical Research, Inc.
Tucson
Arizona
CBCC Global Research, Inc.
Bakersfield
California
UCLA Ronald Regan Medical Center
Los Angeles
California
Yale-New Haven Hospital (YNHH) - Smilow Cancer Hospital
New Haven
Connecticut
BRCR Medical Center
Plantation
Florida
University of South Florida (USF) - H. Lee Moffitt Cancer Center
Tampa
Florida
Franciscan Health
Indianapolis
Indiana
St. Agnes Healthcare, Inc
Baltimore
Maryland
Center for Cancer and Blood Disorders
Bethesda
Maryland
Washington University School of Medicine
St Louis
Missouri
University of New Mexico Cancer Center
Albuquerque
New Mexico
Icahn School of Medicine at Mount Sinai Program for the Protection of Human Subjects
New York
New York
Columbia University Medical Center
New York
New York
Weill Cornell Medical College-New York Presbyterian Hospital
New York
New York
Cleveland Clinic Taussig Cancer
Cleveland
Ohio
The Ohio State Comprehensive Cancer Center
Columbus
Ohio
Prairie lakes Healthcare system, Inc
Watertown
South Dakota
Vanderbilt University Medical - Hematology-Oncology
Nashville
Tennessee
Texas Oncology/Methodist Charlton Cancer Center
Dallas
Texas
Simmons Comprehensive Cancer Center
Dallas
Texas
Fred Hutchinson Cancer Research Center (FHCRC)
Seattle
Washington
ZAS Middelheim
Antwerp
Antwerpen
ZAS Cadix
Antwerp
Antwerpen
GZA Ziekenhuizen - Campus Sint
Wilrijk
Antwerpen
AZ Sint-Jan Burgge-Oostende
Bruges
West-Vlaanderen
Az Groeninge
Kortrijk
West-Vlaanderen
AZ Klina
Brasschaat
Belgium
Universitair Ziekenhuis Gent
Ghent
Belgium
UZ Leuven - Campus Gasthuisberg
Leuven
Belgium
Tom Baker Cancer Centre
Calgary
Alberta
University of Alberta Hospital - Hematology Research
Edmonton
Alberta
The Ottawa Hospital
Ottawa
Ontario
Sunnybrook Health Sciences Centre
Toronto
Ontario
Princess Margaret Hospital
Toronto
Ontario
Jewish General Hospital
Montreal
Quebec
Fakultni nemocnice Brno
Brno
Brno-město
FN Hradec Kralove
Hradec Králové
Hradec Králové
FN Kralovske Vinohrady
Prague
Czechia
Vseobecna fakultni nemocnice v Praze
Prague
Czechia
+ 86 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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