A Phase II Study of Selinexor Plus Cytarabine and Idarubicin in Patients With Relapsed/Refractory Acute Myeloid Leukemia (AML)
Condition: Acute Myeloid Leukemia (Relapsed/Refractory)
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Intervention: Selinexor; Idarubicin; Cytarabine
Intervention description: Patients receive Selinexor as specified in arm/group description (8 doses of 40 mg/m^2 or 6 doses of 60 mg per induction cycle).; Infusion, iv, 10 mg/m^2, on days 1,3,5 in cycle 1, on days 1,3 in cycle 2; Continuous infusion day 1 to 7, 100 mg/m^2, iv,
Intervention MeSH terms: Cytarabine; Idarubicin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Intervention model description: In the initial protocol, 25 patients are included in the clinical trial on the schedule described as cohort 1. After an amendment 15 further patients are included on the schedule described as cohort 2.
Masking: None (Open Label)
Enrollment: 42.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Acute Myeloid Leukemia (AML) is currently treated with chemotherapy by combining several
      drugs with different ways of inhibiting the cell growth. In this trial, standard
      chemotherapeutics that have proven their effectiveness for years, Ara-C and Idarubicin, will
      be combined with a new drug called Selinexor.

      Selinexor inhibits the growth of cancer cells by keeping certain proteins in the nucleus
      which control the cell growth.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Cytological or histological diagnosis of AML with the exception of promyelocytic
             leukemia (AML M3)

          2. Patients must have relapsed/refractory disease (relapse after stem cell
             transplantation is permitted) as defined as:

               1. patients with <PR after first cycle of induction chemotherapy, or

               2. patients with <CR(i) after second cycle of induction chemotherapy, or

               3. patients who relapse after conventional chemotherapy or

               4. patients who have undergone a single stem cell transplantation and who have
                  relapse of their AML.

          3. Men and women aged ≥18 years and eligible for standard dose of chemotherapy (7+3);

          4. A period of at least 3 weeks needs to have elapsed since last treatment (with the
             exception of hydroxyurea) before participating in this study. Hydroxyurea induction
             therapy to reduce peripheral blast counts is permitted prior to initiation of
             treatment on protocol. Treatment may begin in <3 weeks from last treatment if deemed
             in the best interest of the patient after discussion with the PI of the study;

          5. ECOG performance status ≤ 2

          6. Serum biochemical values with the following limits unless considered due to leukemia:
             creatinine ≤2 mg/dl; total bilirubin ≤2x ULN, unless increase is due to hemolysis or
             congenital disorder; transaminases (SGPT or SGOT) ≤2.5x ULN.

          7. Ability to swallow and retain oral medication;

          8. Ability to understand and provide signed informed consent;

          9. Cardiac ejection fraction must be >/=50% (by echocardiography).

         10. Willingness and ability to comply with scheduled visits, treatment plans, laboratory
             tests, and other study procedures.

        Exclusion Criteria:

          1. Treatment with any investigational agent within four weeks.

          2. Cumulative anthracycline dose (daunorubicin or equivalent) >360 mg/m^2

          3. HIV infection

          4. Presence of any medical or psychiatric condition which may limit full compliance with
             the study, including but not limited to:

          5. Presence of CNS leukemia

          6. Unresolved toxicity from previous anti-cancer therapy or incomplete recovery from
             surgery.

          7. For patients after SCT as part of prior treatment:

               1. Necessity of immunosuppressive drugs

               2. GvHD > grade 1

          8. Any of the following within the 12 months prior to study drug administration:
             myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass
             graft, symptomatic congestive heart failure, cerebrovascular accident or transient
             ischemic attack, pulmonary embolism, deep vein thrombosis, or other thromboembolic
             event.

          9. Ongoing cardiac dysrhythmias of NCI CTCAE >/= Grade 2.

         10. Other severe acute or chronic medical or psychiatric condition, or laboratory
             abnormality that may increase the risk associated with study participation or study
             drug administration, or may interfere with the interpretation of study results, and in
             the judgment of the investigator would make the patient inappropriate for entry into
             this study.

         11. Clinically significant bleeding within 1 month