Selinexor (KPT-330) Plus FLAG-Ida for the Treatment of Relapsing/Refractory AML (FLAGINEXOR)
Acute Myeloid Leukemia
About this trial
This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring Acute Myeloid Leukemia, Relapsed, Refractory, Selinexor
Eligibility Criteria
Inclusion Criteria:
- Written informed consent in accordance with national, local, and institutional guidelines. The patient must provide informed consent prior to the first screening procedure.
- Age ≥ 18, and ≤ 65 years old.
- Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
- Diagnosis of AML (defined using WHO criteria) of any type except for acute promyelocytic leukemia (APL; AML M3).
- Relapsing or refractory AML, defined as either:
Recurrence of disease after first CR (duration of CR ≤ 24 months), or Failure to achieve CR or CRi after 1 or 2 identical induction cycles containing an anthracycline plus cytarabine based schedule.
- No contraindications to receive intensive chemotherapy.
- Female patients of child-bearing potential must have a negative serum pregnancy test at screening and agree to use two reliable methods of contraception for three months after their last dose of medication. Male patients must use a reliable method of contraception (if sexually active with a female of child-bearing potential).
- Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other study procedures.
Exclusion Criteria:
- Patients with APL/AML M3.
- Patients who are pregnant or lactating.
- Radiation, chemotherapy, or immunotherapy or any other anticancer therapy ≤ 2 weeks prior to Cycle 1 Day 1 or radio-immunotherapy 4 weeks prior to Cycle 1 Day 1. Hydroxyurea is permitted until 1 day prior to Cycle 1 Day 1.
- Previous treatment with a SINE compound.
- Major surgery within 2 weeks of first dose of study drug.
- Any life-threatening illness, medical condition or organ system dysfunction which, in the Investigator's opinion, could compromise the patient's safety.
Unstable cardiovascular function:
- Symptomatic ischemia, or uncontrolled clinically significant conduction abnormalities (i.e., ventricular tachycardia on anti-arrhythmia are excluded; 1st degree AV block or asymptomatic LAFB/RBBB will not be excluded), or congestive heart failure (CHF) of NYHA Class ≥ 3, or myocardial infarction (MI) within 3 months.
- Uncontrolled (i.e., clinically unstable) infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose; however, prophylactic use of these agents is acceptable even if parenteral.
- Active hepatitis B or hepatitis C infection.
- Known human immunodeficiency virus (HIV) infection (HIV testing is not required as part of this study).
- Patients unable to swallow tablets, patients with malabsorption syndrome, or any other gastrointestinal (GI) disease or GI dysfunction that could interfere with absorption of study treatment.
Any of the following laboratory abnormalities unless due to leukemia:
- Hepatic dysfunction: bilirubin > 2.0 times the upper limit of normal (ULN) (except patients with Gilbert's syndrome: total bilirubin of > 3 x ULN) and alanine aminotransferase (ALT) and aspartic aminotransferase (AST) > 2.5 times ULN or in case of liver metastases: In patients with known liver involvement of their cancer, AST and ALT > 5 x ULN.
- Severe renal dysfunction: estimated creatinine clearance of < 30 mL/min, measured in 24 hour urine or calculated using the formula of Cockroft and Gault: (140-Age) x Mass (kg)/[72 x creatinine (mg/dL)]; multiply by 0.85 if female
Sites / Locations
- Hospital Germans Tries i Pujol, Badalona
- Hospital San Pedro de Alcántara,
- Hospital Universitario 12 de Octubre,
- Hospital la Fe
Arms of the Study
Arm 1
Experimental
Fludarabine-Idarubicine-Cytarabine- Selinexor
fludarabine 30 mg/m2/day intravenously on days 1 to 4, idarubicin 10 mg/m2/day intravenously on days 1 to 3, cytarabine 2 g/m2/day intravenously on days 1 to 4, G-CSF 300 mcg/m2/day subcutaneously from days -1 to 5. This schedule will be combined with oral selinexor (KPT-330) for three weeks at days and dose according to escalation level: Level -1: Selinexor 40 mg/day, once weekly Level 1: Selinexor 60 mg/day, once weekly Level 2: Selinexor 80 mg/day, once weekly Level 3: Selinexor 100 mg/day, once weekly