A phase 2A pilot study to assess the safety and efficacy of eltanexor in relapsed/refractory NPM1-mutated acute myeloid leukemia

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Azienda Ospedaliero Universitaria Delle Marche

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15], Diseases [C] - Neoplasms [C04]

Trial duration

14 Jan 2025 → ongoing

Decision date (initial)

2025-01-13

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Ministero della Salute · Karyopharm Therapeutics Inc.

External identifiers

EU CT number

2024-514724-16-01

EudraCT number

2022-000236-28

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To evaluate the antileukemic activity of eltanexor in relapsed/refractory NPM1-mutated AML
To evaluate the safety and tolerability of eltanexor in relapsed/refractory NPM1-mutated AML

Conditions and MedDRA coding

Acute Myeloid Leukemia

Study design 1 period

Regulatory references

Plan to share IPD

No

IPD plan description

N/A

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. Written informed consent signed prior to any screening procedures and in accordance with local, and institutional guidelines.
2. Age ≥60 years.
3. Documented diagnosis of relapsed or refractory NPM1-mutated AML
4. Life expectancy of at least 3 months at the time of screening.
5. Patient must fall into one of these two categories: a) Patients eligible for standard treatment (intensive chemotherapy) at diagnosis that have received at least one line of standard chemotherapy and one venetoclax-based regimen, unless contraindicated. Additionally, patients with concomitant FLT3 mutations must have received at least one FLT3 inhibitor, unless contraindicated. b) Patients not eligible for standard treatment at diagnosis that have received at least one venetoclax-based regimen, unless contraindicated. Additionally, patients with concomitant FLT3 mutations must have received at least one FLT3 inhibitor, unless contraindicated.
6. Ineligibility for bone marrow transplantation at the time of screening.
7. White blood cell count ≤ 10 x 109/L.
8. A washout time of at least 14 days from the last cytotoxic treatment (except hydroxyurea) and 7 days from the last FLT3 inhibitor.
9. Eastern Cooperative Oncology Group (ECOG) performance status of <2.
10. Ability to swallow oral study medication.
11. Adequate hepatic function: a) total bilirubin ≤2 times the upper limit of normal (ULN) (except patients with Gilbert’s syndrome [hereditary indirect hyperbilirubinemia]. b) aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 times ULN (except patients with known liver involvement of their tumor who must have their AST and ALT ≤5.0 times ULN).
12. Adequate renal function: estimated creatinine clearance of ≥30 mL/min, calculated using the formula of Cockcroft and Gault (140-Age) × Mass (kg)/(72 × creatinine mg/dL); multiply by 0.85 if female.
13. Female patients must be postmenopausal.
14. Male patients must use an effective barrier method of contraception if sexually active. Effective methods of contraception must be used throughout the study and for 6 months following the last dose.

Exclusion criteria 10

1. Major surgery within 4 weeks before C1D1.
2. Impaired cardiac function or clinically significant cardiac diseases, including any of the following: a) Unstable angina or acute myocardial infarction ≤3 months prior to C1D1 b) Clinically significant heart disease (e.g., symptomatic congestive heart failure [e.g., >NYHA Class 2]; uncontrolled arrhythmia, or hypertension; history of labile hypertension or poor compliance with an antihypertensive regimen).
3. Uncontrolled active severe systemic infection requiring parenteral antibiotics, antivirals, or antifungals within 1 week prior to C1D1
4. Known CNS involvement by AML.
5. Known history of human immunodeficiency virus (HIV)
6. Known, active hepatitis A, B, or C infection; or known to be positive for HCV RNA or HBsAg (HBV surface antigen).
7. Patients with gastrointestinal tract disease (or uncontrolled vomiting or diarrhea) that could interfere with the absorption of eltanexor.
8. Serious psychiatric or medical conditions that, in the opinion of the Investigator, could interfere with treatment, compliance, or the ability to give consent.
9. Female patients with childbearing potential.
10. Patients unwilling to comply with the protocol including required biopsies and sample collections required to measure disease.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Response rate (sum of CR, CRi, MLFS) by the end of cycle 2
2. Rate of Grade 5, non-hematological Grade 4 and long-lasting non-hematological Grade 3 adverse events

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Azienda Ospedaliero Universitaria Delle Marche

Sponsor organisation

Azienda Ospedaliero Universitaria Delle Marche

Address

Via Conca 71

City

Ancona

Postcode

60126

Country

Italy

Scientific contact point

Organisation

Azienda Ospedaliero Universitaria Delle Marche

Contact name

Lorenzo Brunetti

Public contact point

Organisation

Azienda Ospedaliero Universitaria Delle Marche

Contact name

Lorenzo Brunetti

Locations

1 EU/EEA country · 3 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 38 files

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

Application history

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