Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at Los Angeles, California and other locations
Dates
study started
completion around
Principal Investigator
by Gary Schiller

Description

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.

Official Title

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

Details

This is a Phase 2/3, multicenter study of imetelstat that consists of 2 parts and approximately 280 participants may be enrolled.

  • Part 1 is an open-label, single-arm design to assess the efficacy and safety of imetelstat. A total of 57 participants were enrolled in Part 1, including the expansion cohort.
  • Part 2 is a double-blind, randomized design to compare the efficacy of imetelstat with placebo. In the main study in Part 2, 178 participants were enrolled and randomized in a 2:1 ratio to receive either imetelstat or placebo, respectively.
  • In a separate Ventricular Repolarization substudy of Part 2, approximately 45 participants will be enrolled and randomized 2:1 to receive either imetelstat or placebo. If after a minimum of 2 treatment cycles in the Ventricular Repolarization substudy, a participant has no significant change to pRBC transfusion burden or evidence of clinical benefit per Investigator, after discussion with the Sponsor the participant may be unblinded. If the participant was on placebo treatment, he/she may be permitted to start treatment with imetelstat.

The Extension Phase will begin after the end of the main study (24 months after the last subject was randomized in the main study of Part 2) and continue until participants who entered Part 2 of the main study participate in the study for up to 5 years from the first dose of imetelstat (including treatment and follow-up), or 3 years of post-treatment follow-up from the last dose of study treatment, whichever occurs later, or until death, withdrawal of consent, study termination, or until a subject is lost to follow-up. Patients ongoing on imetelstat and considered to be benefiting from treatment per Investigator in Part 2 of the study, will have the option to continue receiving imetelstat in the Extension Phase. Patients in the follow-up phase for Part 2 of the study will have the option to continue the follow-up in the Extension Phase.

Part 1 and Part 2 of the study consist of 3 phases: a Screening phase (up to 28 days); a treatment phase; and a post-treatment follow-up phase which will continue until death, lost to follow-up, withdrawal of consent, or the End of the Study (whichever occurs first). The Extension Phase of the study will consist of an extended treatment phase and an extended follow-up phase which will continue until death, lost to follow-up, withdrawal of consent, or the End of the Study (whichever occurs first).

Keywords

Myelodysplastic Syndromes, Imetelstat, GRN163L, Relapsed/refractory to ESAs, Transfusion dependent, IMerge, Preleukemia, Syndrome, Motesanib diphosphate

Eligibility

You can join if…

Open to people ages 18 years and up

  • 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

You CAN'T join if...

  • 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

Locations

  • UCLA Ronald Regan Medical Center
    Los Angeles California 90095 United States
  • CBCC Global Research, Inc.
    Bakersfield California 93309 United States

Lead Scientist at UCLA

  • Gary Schiller
    Professor-in-Residence, Medicine. Authored (or co-authored) 160 research publications

Details

Status
in progress, not accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Geron Corporation
ID
NCT02598661
Phase
Phase 2/3 Myelodysplastic Syndrome Research Study
Study Type
Interventional
Participants
About 289 people participating
Last Updated