Myelofibrosis MedDRA version: 20.0 Level: PT Classification code 10028537 Term: Myelofibrosis System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Geron Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. =18 years of age. 2. Diagnosis of primary MF (PMF) according to the revised WHO criteria (Section 18.2); or PET-MF or PPV-MF according to the IWG-MRT criteria (Section 18.3) confirmed by local pathology report. 3. Dynamic International Prognostic Scoring System intermediate-2 or high-risk MF. 4. Relapsed / Refractory to JAK-inhibitor treatment as defined in either inclusion 4.1, 4.2 or 4.3 and not eligible for ASCT at screening: 4.1: 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: a) no decrease in spleen volume ( 10 cm at the start of JAK inhibitor treatment, at least 50% increase in palpable spleen size from time of best response; AND not a candidate for further JAK inhibitor at screening per investigator. 5. Measurable splenomegaly demonstrated by a palpable spleen measuring = 5 cm below the left costal margin or a spleen volume = 450 cm3 by MRI or CT. 6. Active symptoms of MF on the MFSAF v4.0 (adapted as the MF Symptom Recall Form, Section 18.6) demonstrated by a symptom score of at least 5 points (on a 0 to 10 scale) on at least 1 of the symptoms or a score of 3 or greater on at least 2 of the following symptoms: fatigue, night sweats, itchiness, abdominal discomfort, pain under ribs on left side, early satiety, and bone pain. 7. Hematology laboratory test values within the following limits: • absolute neutrophil count (ANC) = 1.5 x 10^9/L independent of growth factor support, AND • platelets = 75 x 10^9/L independent of platelet transfusion support 8. Biochemical laboratory test values must be within the following limits: • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 2.5 x upper limit of normal (ULN); • Alkaline phosphatase (ALP) = 5 x ULN; • Serum creatinine = 2 x ULN; • Total bilirubin = 3 x ULN; and direct bilirubin = 2 x ULN (unless due to Gilbert’s syndrome or underlying MF). 9. Eastern Cooperative Oncology Group Performance Status score of 0, 1, or 2 10. Women of childbearing potential and men who are sexually active must use a highly effective method of birth control during and after the study consistent with local regulations regarding the use of birth control methods for participants part
Exclusion criteria
Exclusion criteria: 1. Peripheral blood blast count of = 10% or bone marrow blast count of = 10%. 2. Known allergies, hypersensitivity, or intolerance to imetelstat or its excipients. 3. Prior treatment with imetelstat. 4. Any chemotherapy or MF directed therapy, including investigational drug regardless of class or mechanism of action, immunomodulatory or immunosuppressive therapy, corticosteroids > 30 mg/day prednisone or equivalent, and JAK-inhibitor treatment = 14 days prior to randomization. 5. Persistent unresolved toxicity from prior treatment, i.e., has not returned to Grade =1 or pre-treatment baseline. 6. Diagnosis or treatment for malignancy other than MF except: • Malignancy treated with curative intent and with no known active disease present for = 3 years before randomization. • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. • Adequately treated cervical carcinoma in situ without evidence of disease. 7. Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification. 8. Known history of human immunodeficiency virus or any uncontrolled active systemic infection requiring IV antibiotics. 9. 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. 10. Major surgery within 28 days prior to randomization. 11. Female participants who are pregnant or are currently breastfeeding or planning to become pregnant while enrolled in this study or within 30 days after the end of dosing. 12. Male participants who plan to father a child while enrolled in this study or within 90 days after the end of dosing. 13. Any life-threatening illness (e.g., COVID-19), 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; if participant has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (e.g., compromise the well- being) or that could prevent, limit, or confound the protocol-specified assessments.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to compare the overall survival (OS) of participants, treated with imetelstat versus BAT, with intermediate-2 or high-risk Myelofibrosis (MF) whose disease is relapsed / refractory to JAK-inhibitor treatment.;Secondary Objective: to evaluate imetelstat versus BAT with respect to: • Symptom response rate at Week 24, defined as the proportion of participants who have = 50% reduction in total symptom score (TSS) at Week 24 from baseline as measured by the Myelofibrosis Symptom Assessment Form (MFSAF) v4.0 e-diary questionnaire • Progression-free survival, defined as the time interval from randomization date to the first date of disease progression or death from any cause, whichever occurs first • Spleen response rate at Week 24, defined as the proportion of participants who achieve = 35% spleen volume reduction (SVR) at Week 24 from baseline as measured by magnetic resonance imaging (MRI) or computed tomography scan and assessed by Central Radiology Review. Additionally, SVR of = 20% and = 10% at Week 24 will be assessed. • Complete remission, partial remission, clinical improvement, spleen response, symptoms response, and anemia response per modified 2013 IWG MRT criteria see Protocol ;Primary end point(s): The primary endpoint of overall survival (OS) is defined as the time interval from randomization date to date of death from any cause.;Timepoint(s) of evaluation of this end point: date of death from any cause | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - symptom response rate at Week 24 (defined as the proportion of patients who have = 50% reduction in TSS at Week 24 from baseline as measured by the MFSAF v4.0), - spleen response rate at Week 24 (defined as the proportion of patients who achieve = 35% reduction in spleen volume at Week 24 from baseline as measured by imaging scans). See Protocol ;Timepoint(s) of evaluation of this end point: Week 24 See Protocol | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Colombia, Denmark, France, Georgia, Germany, Hungary, India, Israel, Italy, Korea, Republic of, Poland, Portugal, Russian Federation, Singapore, Spain, Switzerland, Taiwan, Turkey, United Kingdom, United States
Contacts
Public ContactClinical Trial Enquiries
Geron Corporation
Outcome results
None listed