A Study to Evaluate Single Agent Selinexor Versus Physician's Choice in Participants with Previously Treated Myelofibrosis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Karyopharm Therapeutics Inc.

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

21 Oct 2021 → ongoing

Decision date (initial)

2024-11-04

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-513605-31-00

EudraCT number

2020-003809-60

ClinicalTrials.gov

NCT04562870

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacogenetic, Pharmacoeconomic, Pharmacodynamic, Efficacy, Safety, Pharmacokinetic

To determine the clinical activity of selinexor monotherapy compared with physician's choice (PC) in patients with previously treated myelofibrosis (MF).

Secondary objectives 5

1. To evaluate additional measures of clinical activity of selinexor compared to physician's choice (PC) in patients with myelofibrosis (MF).
2. To assess the survival outcome of patients with myelofibrosis (MF) receiving selinexor compared with physician's choice (PC).
3. To evaluate additional measures of clinical activity of selinexor compared to physician's choice (PC) in patients with myelofibrosis (MF).
4. To determine the safety profile of selinexor and compare to physician's choice (PC) in patients with myelofibrosis (MF).
5. To characterize pharmacokinetics (PK) of selinexor in patients with myelofibrosis (MF).

Conditions and MedDRA coding

Myelofibrosis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 16

1. A diagnosis of primary MF or post-ET or post-PV MF according to the 2016 WHO classification of MPN, 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 > or = 450 cm3 by MRI or CT scan
4. Relapsed, refractory or intolerant to JAK inhibitors as defined as meeting one of the criteria below: <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 non-hematologic toxicity while on JAK inhibitors
5. Patients > or = 18 years of age
6. ECOG < or = 2
7. Platelet count > or = 75 × 10^9/L
8. Absolute neutrophil count (ANC) > or = 1.5 × 10^9/L
9. Serum direct bilirubin < or =1.5 × ULN; AST and ALT < or = 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 > or = 350 cells/microL, 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 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.
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.

Exclusion criteria 10

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 or growth factors are 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 < or = 7 days prior to selinexor dosing OR strong CYP3A inducers < or = 14 days prior to selinexor dosing.
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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Rate of Spleen Volume Reduction of > or = 35% (SVR35)

Secondary endpoints 6

1. Rate of Total Symptom Score reduction of > or = 50% (TSS50) in the myelofibrosis symptom assessment form (MFSAF) V4.0, based on local assessment
2. Rate of Spleen Volume Reduction of > or =25% (SVR25)
3. Overall survival (OS)
4. Anemia response as defined per the IWG-MRT criteria, based on local assessment • Duration of SVR35 and SVR25 • 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
5. The occurrence, nature, and severity of AEs
6. Population PK derived parameters: • AUC • Cmax

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Karyopharm Therapeutics Inc.

Sponsor organisation

Karyopharm Therapeutics Inc.

Address

85 Wells Avenue

City

Newton

Postcode

02459-3298

Country

United States

Scientific contact point

Organisation

Karyopharm Therapeutics Inc.

Contact name

Clinical Trials Information Desk

Public contact point

Organisation

Karyopharm Therapeutics Inc.

Contact name

Clinical Trials Information Desk

Third parties 8

Locations

2 EU/EEA countries · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications