A Study to Evaluate Safety and Efficacy of Selinexor Versus Treatment of Physician's Choice in Participants With Previously Treated Myelofibrosis

Myelofibrosis Clinical Trial

Official title:

A Phase 2, Randomized, Open-Label, Multicenter Study to Evaluate Safety and Efficacy of Single Agent Selinexor Versus Treatment of Physician's Choice in Patients With Previously Treated Myelofibrosis

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04562870
• Other study ID #: XPORT-MF-035
• Secondary ID: 2020-003809-60
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: March 17, 2021
• Est. completion date: January 6, 2025

Study information

• Verified date: January 2024
• Source: Karyopharm Therapeutics Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase 2, multicenter, two-arm, open-label study to evaluate the safety and efficacy of selinexor versus treatment per physician's choice (PC) in participants with myelofibrosis (MF) who had at least 6 months of treatment with a Janus kinase (JAK)1/2 inhibitor. Study participants will be randomized in a 1:1 ratio to either receive selinexor or physicians' choice of treatment.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 112
• Est. completion date: January 6, 2025
• Est. primary completion date: January 6, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• A diagnosis of primary MF or post-essential thrombocythemia (ET) or post-polycythemia (PV) MF according to the 2016 World Health Organization (WHO) classification of myeloproliferative neoplasms (MPN), confirmed by the most recent local pathology report.
• Previous treatment with JAK inhibitors for at least 6 months.
• Measurable splenomegaly during the screening period as demonstrated by spleen volume of =450 centimeter cube (cm^3) by magnetic resonance imaging (MRI) or computerized tomography (CT) scan.
• Relapsed, Refractory or Intolerant to JAK inhibitors as defined as meeting one of the

criteria below:

• less than (<) 35% spleen volume reduction by MRI or CT-scan (from baseline) or
• <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
• Spleen volume increase greater than (>) 25% from nadir or a return to within 10% of baseline after any initial response or
• Treatment with JAK inhibitor was complicated by development of red blood cells (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
• Participants =18 years of age.
• Eastern Cooperative Oncology Group (ECOG) less than or equal to (=) 2.
• Platelet count =75*10^9 per liter (/L).
• Absolute neutrophil count (ANC) =1.5*10^9/L.
• Serum direct bilirubin =1.5*upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =2.5*ULN.
• Calculated creatinine clearance (CrCl) >15 milliliter (mL)/minute (min) based on the Cockcroft and Gault formula.
• Participants 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 International Units (IU)/mL.
• Participants with untreated hepatitis C virus (HCV) are eligible if there is a documentation of negative viral load per institutional standard.
• Participants with history of human immunodeficiency virus (HIV) are eligible if they have cluster of differentiation 4 (CD4)+ T-cell counts =350 cells/microliter (mcL), negative viral load per institutional standard, and no history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections in the last year.
• Female participants 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 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). Childbearing potential excludes: Age >50 years and naturally amenorrhoeic for >1 year, or previous bilateral salpingo-oophorectomy, or hysterectomy.
• Male participants 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 participants must agree not to donate sperm during the study treatment period.
• Participants must sign written informed consent in accordance with federal, local and institutional guidelines.

Exclusion Criteria:

• >5% blasts in peripheral blood or >10% blasts in bone marrow (i.e., accelerated phase).
• Previous treatment with selinexor or other exportin 1 (XPO1) inhibitors.
• Use of any standard or experimental anti-MF therapy <21 days prior to Cycle 1 Day 1 (hydroxyurea or growth factors are allowed).
• Impairment of gastrointestinal (GI) function or GI disease that could significantly alter the absorption of selinexor (Example: vomiting, or diarrhea that is Common Terminology Criteria for Adverse Events (CTCAE) grade >1).
• Received strong cytochrome P450 3A (CYP3A) inhibitors =7 days prior to selinexor dosing or strong CYP3A inducers =14 days prior to selinexor dosing.
• Major surgery <28 days prior to cycle 1 day 1 (C1D1).
• Uncontrolled (ie, 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).
• Any life-threatening illness, medical condition, or organ system dysfunction which, in the Investigator's opinion, could compromise the participants safety, prevent the participant from giving informed consent, or being compliant with the study procedures.
• Female participants who are pregnant or lactating.
• Participants with contraindications to use of selinexor or all the drugs intended to be used in the comparative treatment arm.

Related Conditions & MeSH terms

• Myelofibrosis
• Primary Myelofibrosis

Intervention

Drug:
• Selinexor
Unit Dose Strength: 20 mg; Dose Formulation: Tablet; Dosage Level: 60 or 80 mg, QW; Route of Administration: Oral

Other:
• Physician's Choice Treatment
Physician's choice treatment may include ruxolitinib retreatment, fedratinib, chemotherapy (e.g., hydroxyurea), anagrelide, corticosteroid, hematopoietic growth factor, immunomodulatory agent, androgen, interferon (all as per clinical practice) and may include supportive care only with no MF treatment; no investigational therapies are allowed.

Locations

Country	Name	City	State
China	Peking Union Medical College Hospital	Beijing	Beijing
China	The First Hospital of Jilin University	Changchun	Jilin
China	Sir Run Run Shaw Hospital - Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	Affiliated Hospital of Nantong University	Nantong	Jiangsu
China	Suzhou University -The First Affiliated Hospital	Suzhou	Jiangsu
China	The Second Affiliated Hospital of Soochow University	Suzhou	Jiangsu
China	Union Hospital, Tongji Medical College, Huazhong University of Science and Technology	Wuhan	Hubei
France	Centre Hospitalier Universitaire d'Angers (CHU Angers)	Angers
France	Institut de Cancéro-Hématologie	Brest	Bretagne
Greece	University General Hospital "ATTIKON"	Athens	Attiki
Italy	Università degli Studi di Firenze - Azienda Ospedaliero - Universitaria Careggi - Dipartimento di medicina sperimentale e clinica	Firenze
Italy	Azienda Unita Sanitaria Locale Latina - Ospedale Santa Maria Goretti	Latina
Italy	Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS	Meldola	Forlì-Cesena
Italy	University of Perugia Department of Medicine Hematology Section	Perugia
Italy	Asst Settelaghi, Ospedale Di Circolo E Fondazione Macchi	Varese
Poland	Pratia Onkologia Katowice	Katowice
Spain	Hospital Universitario 12 de Octubre	Madrid
United States	Rocky Mountain Cancer Centers, LLP	Aurora	Colorado
United States	Illinois Cancer Specialist	Niles	Illinois
United States	The Oncology Institute of Hope and Innovation	Pasadena	California
United States	Texas Oncology - Northeast Texas	Tyler	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Karyopharm Therapeutics Inc

Countries where clinical trial is conducted

United States,  China,  France,  Greece,  Italy,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants with Spleen Volume Reduction of Greater Than or Equal to (=) 35 Percent (%) (SVR35) Assessed by Independent Review Committee (IRC)		From Baseline up to Week 48
Secondary	Percentage of Participants with Total Symptom Score Reduction of =50% (TSS50) Measured by Myelofibrosis Symptom Assessment Form (MFSAF) V4.0, Based on Local Assessment		From Baseline up to end of last cycle (approximately 48 months)
Secondary	Percentage of Participants with Spleen Volume Reduction of =25% (SVR25) Assessed by IRC		From Baseline up to Week 48
Secondary	Overall Survival (OS)		From Baseline up to 12 months after end of treatment (approximately 60 months)
Secondary	Percentage of Participants with Anemia Response Assessed by International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT )		From Baseline up to 28 Days after last dose (approximately 48 months)
Secondary	Duration of Spleen Volume Reduction of =35% (SVR35) Assessed by IRC		From Baseline up to 28 Days after last dose (approximately 48 months)
Secondary	Duration of Spleen Volume Reduction of =25% (SVR25) Assessed by IRC		From Baseline up to 28 Days after last dose (approximately 48 months)
Secondary	Duration of Total Symptom Score is =50% (TSS50) Based on Local Assessment		From Baseline up to 28 Days after last dose (approximately 48 months)
Secondary	Overall Response Rate (ORR) Assessed by IWG-MRT		From Baseline up to 28 Days after last dose (approximately 48 months)
Secondary	Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Severity Grade =3, Serious Adverse event (SAEs), and AEs Leading to Treatment Discontinuation		From first dose of study treatment up to 30 days after end of treatment (approximately 48 months)
Secondary	Pharmacokinetic (PK) Parameter: Area Under the Plasma Concentration-time Curve (AUC) of Selinexor		Cycle 2 Day 1: 1, 2, 4, 6, and 24 hours post dose (each cycle is 28 days)
Secondary	PK Parameter: Maximum Plasma Concentration (Cmax) of Selinexor		Cycle 2 Day 1: 1, 2, 4, 6, and 24 hours post dose (each cycle is 28 days)