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
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.
Study details:
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.
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
Inclusion criteria
- Diagnosis of primary myelofibrosis according to the revised World Health Organization criteria or post-essential thrombocythemia-MF or post-polycythemia vera-MF according to the IWG-MRT criteria
- Dynamic International Prognostic Scoring System intermediate-2 or high-risk MF
- 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:
- Measurable splenomegaly demonstrated by a palpable spleen measuring >= 5 cm below the left costal margin or a spleen volume >= 450 cm^3 by MRI or CT
- Active symptoms of MF on the MFSAF v4.0 demonstrated by a symptom score of at least 5 points (on a 0 to 10 scale)
- Hematology laboratory test values within the protocol defined limits
- Biochemical laboratory test values must be within protocol defined limits
- Eastern Cooperative Oncology Group Performance Status score of 0, 1, or 2
- Participants should follow protocol defined contraceptives procedures
- A woman of childbearing potential must have a negative serum or urine pregnancy test at screening
Exclusion criteria
- Peripheral blood blast count of >= 10% or bone marrow blast count of >=10%
- Known allergies, hypersensitivity, or intolerance to imetelstat or its excipients
- Prior treatment with imetelstat
- Any chemotherapy or MF directed therapy, including investigational drug regardless of class or mechanism of action, immunomodulatory or immunosuppressive therapy, corticosteroids greater than 30 mg/day prednisone or equivalent, and JAK-inhibitor treatment less than equal to 14 days prior to randomization
- Diagnosis or treatment for malignancy other than MF except:
- Known history of human immunodeficiency virus or any uncontrolled active systemic infection requiring IV antibiotics
- Active systemic hepatitis infection requiring treatment (carriers of hepatitis virus are permitted to enter the study), or any known acute or chronic liver disease requiring treatment unless related to underlying hepatosplenomegaly due to MF
- Major surgery within 28 days prior to randomization
- Any life-threatening illness (e.g., coronavirus disease-2019), medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the participant's safety, interfere with the imetelstat metabolism, or put the study outcomes at undue risk
Eligibility
Age eligible for study : NA
Healthy volunteers accepted : No
Gender eligible for study: ALL
Things to know
Study dates
Study start:
Primary completion:
Study completion finish:
Study type
TREATMENT
Phase
- PHASE3
Study ID
NCT04576156
Intervention or treatment
DRUG: Imetelstat
DRUG: Best Available Therapy (BAT)
Conditions
- Myelofibrosis
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Research sites nearby
Closest Location:
Royal North Shore Hospital
Select from list below to view details:
Royal North Shore Hospital
St Leonards, New South Wales, Australia
Royal Brisbane and Women's Hospital
Herston, Queensland, Australia
Royal Hobart Hospital
Hobart, Tasmania, Australia
Epworth Healthcare
Richmond, Victoria, Australia
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Who is running the clinical trial?
Geron Corporation
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
| Participant Group/Arm | Intervention/Treatment |
|---|---|
EXPERIMENTAL: Imetelstat
| Drug: Imetelstat |
ACTIVE_COMPARATOR: Best Available Therapy (BAT)
| Drug: Best Available Therapy (BAT) |
What is the study measuring?
Primary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| Overall survival (OS) | Overall survival is defined as the time interval from randomization date to date of death from any cause. | Baseline (Day 1) until End of Study (EOS) (approximately 3 years )] |
Secondary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| Symptom response rate | The proportion of participants achieving a ≥50% reduction in Total Symptom Score (TSS) measured at Week 24 compared to baseline | 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. | 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. | 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. | 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. | 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 | Screening (Day -28 to -1) until End of Study (approximately 3 years) |
| Assessment of Cmax | Maximum Observed Plasma Concentration (Cmax). | Day 1 of all cycles (each cycle is 21 days) |
| Assessment of Tmax | Time to reach the maximum observed plasma concentration | Day 1 of all cycles (each cycle is 21 days) |
| Assessment of t1/2 | Elimination half-life. | 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 | 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. | 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). | Baseline to End of Study (approximately 3 years) |
References
Clinical Trials Gov: 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 TreatmentOther trials to consider
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