A Study Comparing Imetelstat Versus Best Available Therapy for the Treatment of Intermediate-2 or High-risk Myelofibrosis (MF) Who Have Not Responded to Janus Kinase (JAK)-Inhibitor Treatment
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|ClinicalTrials.gov Identifier: NCT04576156|
Recruitment Status : Recruiting
First Posted : October 6, 2020
Last Update Posted : January 13, 2023
|Condition or disease||Intervention/treatment||Phase|
|Myelofibrosis||Drug: Imetelstat Drug: Best Available Therapy (BAT)||Phase 3|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||320 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Randomized Open-Label, Phase 3 Study to Evaluate Imetelstat (GRN163L) Versus Best Available Therapy (BAT) in Patients With Intermediate-2 or High-risk Myelofibrosis (MF) Relapsed / Refractory (R/R) to Janus Kinase (JAK) Inhibitor|
|Actual Study Start Date :||April 12, 2021|
|Estimated Primary Completion Date :||August 27, 2025|
|Estimated Study Completion Date :||August 27, 2025|
Participants will receive imetelstat at 9.4 mg/kg intravenous (IV) every 21 days (±3 days), until disease progression or unacceptable toxicity, treatment discontinuation or study end.
Imetelstat will be given intravenously at 9.4 mg/kg every 21 days, until disease progression or unacceptable toxicity, treatment discontinuation or study end.
Other Name: GRN163L
Active Comparator: Best Available Therapy (BAT)
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)
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) [ Time Frame: Baseline (Day 1) until End of Study (EOS) (approximately 3 years )] ]Overall survival is defined as the time interval from randomization date to date of death from any cause.
- Symptom response rate [ Time Frame: Baseline (Day 1), and at Week 24 ]The proportion of participants achieving a ≥50% reduction in Total Symptom Score (TSS) measured at Week 24 compared to baseline
- Progression-free survival [ Time Frame: Baseline (Day 1) until End of Study (EOS) (approximately 3 years) ]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.
- Spleen response rate [ Time Frame: Baseline (Day 1), and at Week 24 ]The proportion of participants who achieve a reduction in spleen volume of ≥ 35% from baseline 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 [ Time Frame: Baseline (Day 1) until End of Treatment (approximately 3 years) ]The proportion of participants achieving CR or PR, CI, spleen response, symptom response, and anemia response per modified 2013 IWG-MRT criteria.
- Reduction in the degree of bone marrow fibrosis [ Time Frame: Baseline (Day 1) until End of Treatment (approximately 3 years) ]Reduction in the degree of bone marrow fibrosis will be assessed.
- Number of Participants with Adverse Events [ Time Frame: Screening (Day -28 to -1) until End of Study (approximately 3 years) ]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
- Assessment of Cmax [ Time Frame: Day 1 of all cycles (each cycle is 21 days) ]Maximum Observed Plasma Concentration (Cmax).
- Assessment of Tmax [ Time Frame: Day 1 of all cycles (each cycle is 21 days) ]Time to reach the maximum observed plasma concentration
- Assessment of t1/2 [ Time Frame: Day 1 of all cycles (each cycle is 21 days) ]Elimination half-life.
- Assessment of AUC [ Time Frame: Day 1 of all cycles (each cycle is 21 days) ]Area under the drug concentration-plasma time curve (AUC) from time zero to last measurable concentration
- European Organization for Research and Treatment of Cancer Quality-of-Life-Questionnaire-Core-30 (EORTC QLQ-C30) scores [ Time Frame: Baseline to End of Study (approximately 3 years) ]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.
- EuroQol-EQ-5D (EQ-5D-5L) questionnaire scores [ Time Frame: Baseline to End of Study (approximately 3 years) ]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).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04576156
|Contact: Tymara Berry, MD||650-473-7745||myf3001-info@Geron.com|
|Contact: Denise Redding||myf3001-info@Geron.com|
|Study Director:||Faye Feller||Geron Corporation|