Selinexor (KPT-330) Plus FLAG-Ida for the Treatment of Relapsing/Refractory AML

• Status: Completed
• Trial end date: 2019-10-15
• Target enrollment: 0
• Participant gender: All

Summary

This protocol corresponds to a multicenter, open-label, non-randomized, phase I study designed to determine the safety of the combination of selinexor with chemotherapy in young patients with relapsed or refractory AML.

The clinical trial is divided into pre-treatment, treatment (induction and consolidation cycles) and follow-up periods and consists of a phase I design in which es-calating doses of selinexor will be given to 3 groups, each with 3-6 patients until achieving the maximum tolerated dose (MTD).

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: PETHEMA Foundation
• Treatments: Cytarabine; Fludarabine; Fludarabine phosphate; Idarubicin; Vidarabine

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