A Phase 3 interventional study of Imetelstat and Best Available Therapy (BAT) in Myelofibrosis, sponsored by Geron Corporation. Active, not recruiting at 144 sites in 26 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-07-08.
Sponsored by Geron Corporation · Phase 3, Interventional, and Treatment
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 (R/R) to Janus Kinase (JAK)-Inhibitor treatment.
This is a multicenter study with 2 arms, and will include 3 phases: a) screening phase of up to 28 days before randomization during which participants will complete a 14-day washout period from all prior therapies including JAK-inhibitor treatment, and the participant's eligibility will be reviewed; b) treatment phase, from randomization until study treatment (imetelstat or BAT) discontinuation; and c) post treatment follow-up phase, that begins when the participant discontinues treatment, and will continue until death, lost to follow-up, withdrawal of consent, or study end, whichever occurs first. Participants will be randomized (2:1) into 2 Arms (Arm A will receive imetelstat and Arm B will receive BAT).
Participants who meet progressive disease criteria and discontinue BAT, may crossover to receive imetelstat treatment after sponsor's approval.
Relapsed/refractory to JAK-inhibitor treatment as defined in either inclusion (i), (ii) or (iii) and not eligible for allogeneic stem cell transplantation (ASCT) at screening:
(i) Treatment with JAK-inhibitor for >= 6 months duration, including at least 2 months at an optimal dose as assessed by the investigator for that participant and at least one of the following:
(iii) Following maximum tolerated doses of JAK inhibitor therapy for ≥3 months duration, having documented relapsed disease defined as either
Increase in spleen size by palpation, CT, or ultrasound
AND not a candidate for further JAK inhibitor at screening per investigator.
Exclusion Criteria:
Diagnosis or treatment for malignancy other than MF except:
Participants will receive imetelstat sodium at 9.4 mg/kg intravenous (IV) every 21 days (±3 days), until disease progression or unacceptable toxicity, treatment discontinuation or study end.
Drug: Imetelstat
Participants will receive BAT (investigator-selected non-JAK-inhibitor treatment), until disease progression or unacceptable toxicity, treatment discontinuation or study end. Participants on BAT who meet protocol-defined criteria for progressive disease may crossover to receive imetelstat treatment after sponsor's approval.
Drug: Best Available Therapy (BAT)
Imetelstat sodium will be given intravenously at 9.4 mg/kg every 21 days, until disease progression or unacceptable toxicity, treatment discontinuation or study end.
Also known as: GRN163L
Non-JAK-inhibitor treatment will be given, which may include but is not limited to hydroxyurea, thalidomide or an analog of thalidomide, interferon, danazol, hypomethylating agents, chemotherapy or radiotherapy.
Overall survival (OS)
Overall survival is defined as the time interval from randomization date to date of death from any cause.
Time frame: Baseline (Day 1) until End of Study (EOS) (approximately 3 years )]
Symptom response rate
The proportion of participants achieving a ≥50% reduction in Total Symptom Score (TSS) measured at Week 24 compared to baseline
Time frame: Baseline (Day 1), and at Week 24
Progression-free survival
Progression-free survival is defined as the time interval from randomization date to the first date of disease progression (worsening splenomegaly or leukemic transformation per 2013 International Working Group - Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) criteria) or death from any cause, whichever occurs first.
Time frame: Baseline (Day 1) until End of Study (EOS) (approximately 3 years)
Spleen response rate
The proportion of participants who achieve a reduction in spleen volume of ≥ 35% from baseline at Week 24.
Time frame: 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
The proportion of participants achieving CR or PR, CI, spleen response, symptom response, and anemia response per modified 2013 IWG-MRT criteria.
Time frame: Baseline (Day 1) until End of Treatment (approximately 3 years)
Reduction in the degree of bone marrow fibrosis
Reduction in the degree of bone marrow fibrosis will be assessed.
Time frame: Baseline (Day 1) until End of Treatment (approximately 3 years)
Number of Participants with Adverse Events
Safety will be assessed based on the incidence and severity (according to the Common Terminology Criteria for Adverse Events) of treatment emergent adverse events from the time of randomization until 30 days after completion of treatment
Time frame: Screening (Day -28 to -1) until End of Study (approximately 3 years)
Assessment of Cmax
Maximum Observed Plasma Concentration (Cmax).
Time frame: Day 1 of all cycles (each cycle is 21 days)
Assessment of Tmax
Time to reach the maximum observed plasma concentration
Time frame: Day 1 of all cycles (each cycle is 21 days)
Assessment of t1/2
Elimination half-life.
Time frame: Day 1 of all cycles (each cycle is 21 days)
Assessment of AUC
Area under the drug concentration-plasma time curve (AUC) from time zero to last measurable concentration
Time frame: 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
Patient-reported outcomes including health-related quality of life, pain, and overall change in participant's health will be assessed using the EORTC QLQ-C30. The EORTC QLQ-C30 includes 30 items resulting in 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 Global Health Status scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Scores are transformed to a 0 to 100 scale. Higher scores indicated worse outcome.
Time frame: Baseline to End of Study (approximately 3 years)
EuroQol-EQ-5D (EQ-5D-5L) questionnaire scores
EQ-5D-5L is a 5 item questionnaire that assesses 5 domains including mobility, self-care, usual activities, pain/discomfort and anxiety/depression plus a visual analog scale rating "health today" with anchors ranging from 0 (worst imaginable health state) to 100 (best imaginable health state).
Time frame: Baseline to End of Study (approximately 3 years)
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This study is active, not recruiting, as verified in Jun 2026. You cannot join it, but the record below documents what was studied.
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Geron Corporation