ELTANEXOR for Acute myeloid leukemia|NPM1-mutated acute myeloid leukemia|Relapsed/refractory acute myeloid leukemia

Inclusion criteria

• {"criterion_text":"- Written informed consent signed prior to any screening procedures and in accordance with local, and institutional guidelines.\n- Ability to swallow oral study medication.\n- 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).\n- 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.\n- Female patients must be postmenopausal.\n- 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.\n- Age ≥60 years.\n- Documented diagnosis of relapsed or refractory NPM1-mutated AML\n- Life expectancy of at least 3 months at the time of screening.\n- 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.\n- Ineligibility for bone marrow transplantation at the time of screening.\n- White blood cell count ≤ 10 x 109/L.\n- A washout time of at least 14 days from the last cytotoxic treatment (except hydroxyurea) and 7 days from the last FLT3 inhibitor.\n- Eastern Cooperative Oncology Group (ECOG) performance status of <2."}

Exclusion criteria

• {"criterion_text":"- Major surgery within 4 weeks before C1D1.\n- Patients unwilling to comply with the protocol including required biopsies and sample collections required to measure disease.\n- 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).\n- Uncontrolled active severe systemic infection requiring parenteral antibiotics, antivirals, or antifungals within 1 week prior to C1D1\n- Known CNS involvement by AML.\n- Known history of human immunodeficiency virus (HIV)\n- Known, active hepatitis A, B, or C infection; or known to be positive for HCV RNA or HBsAg (HBV surface antigen).\n- Patients with gastrointestinal tract disease (or uncontrolled vomiting or diarrhea) that could interfere with the absorption of eltanexor.\n- Serious psychiatric or medical conditions that, in the opinion of the Investigator, could interfere with treatment, compliance, or the ability to give consent.\n- Female patients with childbearing potential."}

Primary endpoints

• {"endpoint_text":"- Response rate (sum of CR, CRi, MLFS) by the end of cycle 2","definition_or_measurement_approach":"Response rate defined as the sum of complete remission (CR), CR with incomplete hematologic recovery (CRi), and morphologic leukemia-free state (MLFS) assessed by the end of cycle 2."}
• {"endpoint_text":"- Rate of Grade 5, non-hematological Grade 4 and long-lasting non-hematological Grade 3 adverse events","definition_or_measurement_approach":"Rate of specified severe non-hematological adverse events (Grade 5, Grade 4 non-hematological, and long-lasting Grade 3 non-hematological events) as reported in safety assessments."}

Italy

Earliest CTIS Part Ii Submission Date

07-11-2024

Latest Decision Or Authorization Date

13-04-2026

Processing Time Days

522

Number Of Sites

3

Number Of Participants

10

Primary sponsor

Full Name

Azienda Ospedaliero Universitaria Delle Marche

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Italy

Third parties

• {"country":"","full_name":"Ministero della Salute","duties_or_roles":"Source of monetary support","organisation_type":""}
• {"country":"","full_name":"Karyopharm Therapeutics Inc.","duties_or_roles":"Source of monetary support","organisation_type":""}