A study comparing current available therapies with imetelstat for the treatment of intermediate-2 or high-risk MF who are not responding to JAK-inhibitor treatment
- Conditions
- Myelofibrosis
- Interventions
- Drug: -
- Registration Number
- 2023-509120-17-00
- Lead Sponsor
- Geron Corp.
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing, recruiting
- Sex
- Not specified
- Target Recruitment
- 260
Diagnosis of 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.
Dynamic International Prognostic Scoring System intermediate-2 or high-risk MF (Section 18.4).
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% by MRI or CT) from the start of treatment with JAK-inhibitor. b) no decrease in spleen size (< 30% by palpation or length by imaging) from start of treatment with JAK-inhibitor. c) no decrease in symptoms (< 20% by MFSAF or myeloproliferative neoplasm SAF) from start of treatment with JAK-inhibitor. d) a score of at least 15 on TSS assessed using the MFSAF v4.0 (adapted as the MF Symptom Recall Form, Section 18.6) during screening. 4.2: Treatment with JAK-inhibitor for ≥ 3 months duration with maximal doses for that participant (e.g. 20-25 mg twice daily ruxolitinib) without a spleen or symptom response as defined in inclusion criterion 4.1 (a, b, or c) and would not benefit from remaining on treatment for 6 months. 4.3: Following maximum tolerated doses of JAK inhibitor therapy for ≥3 months duration, having documented relapsed disease defined as either: • Increase in spleen volume from time of best response by 25% measured by MRI or CT, or • Increase in spleen size by palpation, CT, or ultrasound - For splenomegaly of 5-10 cm at the start of JAK inhibitor treatment, at least 100% increase in palpable spleen size from time of best response; - For splenomegaly of > 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.
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.
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.
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.
Peripheral blood blast count of ≥ 10% or bone marrow blast count of ≥ 10%.
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 > 30 mg/day prednisone or equivalent, and JAK-inhibitor treatment ≤ 14 days prior to randomization.
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.
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.
Known history of human immunodeficiency virus or any uncontrolled active systemic infection requiring IV antibiotics.
Study & Design
- Study Type
- Not specified
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description - - Participants receiving -
- Primary Outcome Measures
Name Time Method Overall survival (OS), defined as the time interval from randomization date to date of death from any cause. Overall survival (OS), defined as the time interval from randomization date to date of death from any cause.
- Secondary Outcome Measures
Name Time Method 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) 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). For additional secondary end points please refer to the study protocol. 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). For additional secondary end points please refer to the study protocol.
Progression-Free Survival, defined as the time interval from randomization date to the first date of disease progression (worsening splenomegaly or leukemic transformation per 2013 IWG-MRT criteria) or death from any cause, whichever occurs first. Progression-Free Survival, defined as the time interval from randomization date to the first date of disease progression (worsening splenomegaly or leukemic transformation per 2013 IWG-MRT criteria) or death from any cause, whichever occurs first.
Trial Locations
- Locations (80)
IRCCS Ospedale Policlinico San Martino
🇮🇹Genoa, Italy
Azienda Unita Sanitaria Locale Della Romagna
🇮🇹Ravenna, Italy
Azienda USL IRCCS Di Reggio Emilia
🇮🇹Reggio Emilia, Italy
Azienda Ospedaliera Ospedale Di Circolo E Fondazione Macchi
🇮🇹Varese, Italy
Ospedale S. Eugenio, ASL Roma 2
🇮🇹Roma, Italy
Azienda Ospedaliera Universitaria Federico II Di Napoli
🇮🇹Naples, Italy
Humanitas Research Hospital
🇮🇹Rozzano, Italy
Azienda Unita Locale Socio Sanitaria N 8 Berica
🇮🇹Vicenza, Italy
University Hospital Of Ferrara
🇮🇹Ferrara, Italy
Azienda Ospedaliera Nazionale Ss Antonio E Biagio E C Arrigo Alessandria
🇮🇹Alexandria, Italy
Scroll for more (70 remaining)IRCCS Ospedale Policlinico San Martino🇮🇹Genoa, ItalyRoberto LemoliSite contact00390105554337roberto.lemoli@unige.itMatteo Emidio DraganiSite contact+390105553021Matteoemidio.dragani@hsanmartino.it