Phase 2
Completed N=107
Study to Evaluate Activity of 2 Dose Levels of Imetelstat in Participants With Intermediate-2 or High-Risk Myelofibrosis (MF) Previously Treated With Janus Kinase (JAK) Inhibitor
Source: ClinicalTrials.gov NCT02426086 ↗Enrolled (actual)
107
Serious AEs
41.2%
Results posted
Sep 2021
Primary outcomePrimary: Percentage of Participants With Spleen Response — 0; 10.2 percentage of participants
Summary
The purpose of this study is to evaluate the efficacy and safety of 2 dose regimens of imetelstat in participants with intermediate-2 or high-risk myelofibrosis (MF) whose disease is relapsed after or is refractory to Janus Kinase (JAK) inhibitor treatment. Key secondary endpoint includes overall survival.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With Spleen Response |
0; 10.2 | — |
| PRIMARY Percentage of Participants With Symptom Response |
6.3; 32.2 | — |
| SECONDARY Percentage of Participants With Overall Response as Per Modified 2013 International Working Group - Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) Criteria |
0; 1.7 | — |
| SECONDARY Percentage of Participants With Clinical Improvement (CI) Per Modified 2013 IWG-MRT Criteria |
16.7; 25.4 | — |
| SECONDARY Percentage of Participants With Clinical Response Per Modified 2013 IWG-MRT |
16.7; 27.1 | — |
| SECONDARY Percentage of Participants With Spleen Response Per Modified 2013 IWG-MRT Criteria |
0; 3.4; 2.1; 0 | — |
| SECONDARY Percentage of Participants With Symptoms Response Per Modified 2013 IWG-MRT Criteria |
14.6; 22.0; 4.2; 8.5 | — |
| SECONDARY Percentage of Participants With Anemia Response Per Modified 2013 IWG-MRT Criteria |
4.2; 6.8; 0; 1.7 | — |
| SECONDARY Duration of Response (PR/CI/RWCI) as Per IWG-MRT Criteria |
36.3; 38.3 | — |
| SECONDARY Overall Survival |
19.91; 28.09 | — |
| SECONDARY Percentage of Participants With Clinically Meaningful Improvement in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-30 (QLQ-C30): Global Health Status |
22.2; 36.4 | — |
| SECONDARY EuroQol 5 Dimension 5 Level (EQ-5D-5L): Utility Score and Visual Analog Scale (VAS) |
0.498; 0.626; 51.28; 47.73 | — |
| SECONDARY Percentage of Participants With Clinically Meaningful Improvement in Brief Pain Inventory (BPI) |
50.0; 75.8; 44.4; 51.5; 55.6; 66.7 | — |
| SECONDARY Patient's Global Impression of Change (PGIC) |
4.82; 3.97 | — |
| SECONDARY Number of Participants With Treatment-emergent Adverse Events (TEAEs) |
47; 59 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) of Imetelstat |
57.0; 81.9 | — |
| SECONDARY Time to Reach Maximum Observed Plasma Concentration (Tmax) of Imetelstat |
2.00; 2.00 | — |
| SECONDARY Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC 0-24) of Imetelstat |
171; 501 | — |
| SECONDARY Area Under the Plasma Concentration-Time Profile From Time Zero to Infinity (AUC0-inf) of Imetelstat |
193; 524 | — |
| SECONDARY Elimination Half-Life (t1/2) of Imetelstat |
4.6; 5.5 | — |
| SECONDARY Total Systemic Clearance (CL) of Imetelstat |
0.0329; 0.0252 | — |
| SECONDARY Volume of Distribution (Vd) of Imetelstat |
0.198; 0.190 | — |
Eligibility Criteria
Inclusion Criteria
- Diagnosis of primary myelofibrosis (PMF) according to the revised WHO criteria; or post-essential thrombocythemia-myelofibrosis (PET-MF) or post-polycythemia vera-myelofibrosis (PPV-MF) according to the International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) criteria.
- Dynamic International Prognostic Scoring System (DIPSS) intermediate-2 or highrisk MF.
- Measurable splenomegaly prior to study entry as demonstrated by palpable spleen measuring ≥ 5 cm below the left costal margin OR spleen volume of ≥ 450 cm^3 measured by magnetic resonance imaging (MRI).
- Active symptoms of MF as demonstrated by a symptom score of at least 5 points (on a 0 to 10 scale) on at least one of the symptoms or a score of 3 or greater on at least 2 of the symptoms.
- Documented progressive disease during or after Janus kinase (JAK) inhibitor therapy.
- Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2.
Exclusion Criteria
- Peripheral blood blast count of ≥ 10% or bone marrow blast count of ≥ 10%.
- Prior treatment with imetelstat.
- Any chemotherapy or MF-directed therapy, investigational drug, hydroxyurea, immunomodulatory or immunosuppressive therapy, corticosteroids or JAK inhibitor therapy ≤14 days prior to randomization.
- Major surgery within 4 weeks prior to randomization.
- Active systemic hepatitis infection requiring treatment (carriers of hepatitis virus are permitted to enter the study), of any type or known acute or chronic liver disease including cirrhosis.
- Prior history of hematopoietic stem cell transplant.
Data sourced from ClinicalTrials.gov (NCT02426086). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.