Studio per valutare la sicurezza e l'efficacia del selinexor vs. trattamento di scelta del medico in pazienti con mielofibrosi già precedentemente trattata.

Phase 1

• Conditions: Myelofibrosis; MedDRA version: 20.0Level: PTClassification code 10028537Term: MyelofibrosisSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: PTClassification code 10077161Term: Primary myelofibrosisSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.0Level: LLTClassification code 10074689Term: Post polycythemia vera myelofibrosisSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: LLTClassification code 10074691Term: Post polycythaemia vera myelofibrosisSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.0Level: LLTClassification code 10074690Term: Post essential thrombocythemia myelofibrosisSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2020-003809-60-IT
• Lead Sponsor: KARYOPHARM THERAPEUTICS, INC.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-07-27
• Last Update Posted: 2 March 2022

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 112

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. <35% spleen volume reduction by MRI or CT-scan (from baseline) or
b. <50% decrease in spleen size by palpation (from baseline) or an increase of at least 3 cm with the spleen at least 5 cm below the left
costal margin or
c. Spleen volume increase >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 nonhematologic toxicity while on JAK inhibitors
5. Patients =18 years of age
6. ECOG =2
7. Platelet count =100 × 109/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
<100 IU/mL.
12. Patients with untreated hepatitis C virus (HCV) are eligible if there is a documentation of negative viral load per institutional standard.
13. Patients with history of human immunodeficiency virus (HIV) are eligible if they have CD4+ T-cell counts =350 cells/µL, negative viral
load per institutional standard, and no history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections in the last year.
14. Female patients of childbearing potential must have a negative serum pregnancy test at screening and agree to use highly effective
methods of contraception throughout the study and for one month following the last dose of study treatment. Childbearing potential excludes: Age >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 one month following the last dose of study treatment. 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.
Il crossover dal braccio scelto dal medico (PC) al braccio selinexor (S) sarà consentito per i pazienti che sviluppano malattia progressiva (aumento> 25%) o per quelli con riduzione <35% alla settimana 36. I pazienti devono soddisfare tutti i criteri di inclusione ed esclusione prima del crossover. I pazienti che hanno superato il crossover a causa di PD (aumento> 25%) confermato da IRC o per riduzione <35% delle dimensioni della milza alla settimana 36, dovrebbero avere un wash-out di 10 giorni dall'ultima dose nel braccio PC.
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

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 <21 days prior to Cycle 1 Day 1 (hydroxyurea is allowed).
4. Impairment of gastrointestinal (GI) function or GI disease that could significantly alter the absorption of selinexor (Example: vomiting, or
diarrhea that is CTCAE grade >1).
5. Received strong cytochrome P450 3A (CYP3A) inhibitors =7 days prior o 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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified