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) MedDRA version: 21.0 Level: LLT Classification code 10074689 Term: Post polycythemia vera myelofibrosis System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.0 Level: LLT Classification code 10074690 Term: Post essential thrombocythemia mye
Conditions
Sponsors
Karyopharm Therapeutics Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients are eligible to be included in the study only if they meet all of the following criteria: Main Inclusion Criteria 1. A diagnosis of primary MF or post-ET or post-PV MF according to the 2016 WHO classification of MPN (Protocol Appendix 2), confirmed by the most recent local pathology report. 2. Previous treatment with JAK inhibitors for at least 6 months. 3. Measurable splenomegaly during the screening period as demonstrated by spleen volume of =450 cm3 by MRI or CT scan 4. Relapsed, refractory or intolerant to JAK inhibitors as defined as meeting one of the criteria below: a. 25% from nadir or a return to within 10% of baseline after any initial response or d. Treatment with JAK inhibitor was complicated by development of RBC transfusion requirement (2 units per month for 2 month); or grade 3 thrombocytopenia, anemia, hematoma/hemorrhage; or Grade 2 non- hematologic toxicity while on JAK inhibitors 5. Patients =18 years of age 6. ECOG =2 7. Platelet count =75 × 10^9/L 8. Absolute neutrophil count (ANC) =1.5 × 109/L 9. Serum direct bilirubin =1.5 × ULN; AST and ALT = 2.5 × ULN 10. Calculated creatinine clearance (CrCl) >15 mL/min based on the Cockcroft and Gault formula. 11. Patients with active hepatitis B virus (HBV) are eligible if antiviral therapy for hepatitis B has been given for >8 weeks and viral load is 50 years and naturally amenorrhoeic for >1 year, or previous bilateral salpingo-oophorectomy, or hysterectomy. 15. Male patients who are sexually active must use highly effective methods of contraception throughout the study and for at least 90 days after the last dose of selinexor, or for the duration as stated on the label (SmPC/USPI) for those on the comparator drug (physician's choice arm). Male patients must agree not to donate sperm during the study treatment period. 16. Patients must sign written informed consent in accordance with federal, local and institutional guidelines. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 23 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 89
Exclusion criteria
Exclusion criteria: Patients are excluded from the study if any of the following criteria apply: 1. >5% blasts in peripheral blood or >10% blasts in bone marrow (i.e., accelerated phase). 2. Previous treatment with selinexor or other XPO1 inhibitors. 3. Use of any standard or experimental anti-MF therapy 1). 5. Received strong cytochrome P450 3A (CYP3A) inhibitors =7 days prior to selinexor dosing OR strong CYP3A inducers =14 days prior to selinexor dosing (Protocol Appendix 3). 6. Major surgery <28 days prior to C1D1. 7. Uncontrolled (i.e., clinically unstable) infection requiring parenteral antibiotics, antivirals, or antifungals within 7 days prior to first dose of study treatment; however, prophylactic use of these agents is acceptable (including parenteral). 8. Any life-threatening illness, medical condition, or organ system dysfunction which, in the Investigator’s opinion, could compromise the patient’s safety, prevent the patient from giving informed consent, or being compliant with the study procedures. 9. Female patients who are pregnant or lactating. 10. Patients with contraindications to use of selinexor or all the drugs intended to be used in the comparative treatment arm.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the clinical activity of selinexor monotherapy compared with physician’s choice (PC) in patients with previously treated myelofibrosis (MF).;Secondary Objective: Key Secondary • To evaluate additional measures of clinical activity of selinexor compared to physician’s choice (PC) in patients with myelofibrosis (MF). Other Secondary • To assess the survival outcome of patients with myelofibrosis (MF) receiving selinexor compared with physician’s choice (PC). • To evaluate additional measures of clinical activity of selinexor compared to physician’s choice (PC) in patients with myelofibrosis (MF). • To determine the safety profile of selinexor and compare to physician’s choice (PC) in patients with myelofibrosis (MF). • To characterize pharmacokinetics (PK) of selinexor in patients with myelofibrosis (MF). Exploratory: • To evaluate patient reported outcomes in patients with MF receiving selinexor compared to PC. • To identify predictive biomarkers of response to treatment and explore treatment mechanism of action in patients with MF. • Assess changes in transfusion requirements • Assess changes in serum LDH levels;Primary end point(s): Rate of Spleen Volume Reduction of =35% (SVR35) based on the response assessment by the Independent Radiology Committee (IRC) ;Timepoint(s) of evaluation of this end point: From Baseline up to Week 48 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key Secondary • Rate of Total Symptom Score reduction of =50% (TSS50) in the myelofibrosis symptom assessment form (MFSAF) V4.0, based on local assessment • Rate of Spleen Volume Reduction of =25% (SVR25) based on the response assessment by the Independent Radiology Committee (IRC) Other Secondary • Overall survival (OS) • Anemia response as defined per the IWG-MRT (International Working Group – Myeloproliferative Neoplasms Research and Treatment) criteria, based on local assessment • Duration of SVR35 and SVR25, based on IRC assessment • Duration of TSS50, based on local assessment • ORR (Complete Response [CR] + Partial Response [PR] + Clinical Improvement [CI]) by IWG-MRT criteria, based on local assessment The occurrence, nature, and severity of AEs Population PK derived parameters: • AUC • Cmax;Timepoint(s) of evaluation of this end point: Key Secondary Endpoints • From Baseline up to end of last cycle (approximately 48 months) • From Baseline up to Week 48 Other Secondary Endpoints • From Baseline up to 12 months after end of treatment (approximately 60 months) • From Baseline up to 28 Days after last dose (approximately 48 months) • From Baseline up to 28 Days after last dose (approximately 48 months) • From Baseline up to 28 Days after last dose (approximately 48 months) • From Baseline up to 28 Days after last dose (approximately 48 months) From first dose of study treatment up to 30 days after end of treatment (approximately 48 months) ] PK parameter: Cycle 2 Day 1: 1, 2, 4, 6, and 24 hours post dose (each cycle is 28 days) | — |
Countries
Austria, France, Greece, Hungary, Italy, Poland, Spain, United Kingdom, United States
Contacts
Public ContactClinical Trial Information Desk
Karyopharm Therapeutics Inc.
Outcome results
None listed