Selinexor (KPT-330) in Older Patients With Relapsed AM

Phase 1

Conditions: Acute Myeloid Leukemia (AML)
MedDRA version: 20.0Level: LLTClassification code 10000886Term: Acute myeloid leukemiaSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2014-000920-26-BE

Lead Sponsor: Karyopharm Therapeutics, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 340

Inclusion Criteria

In order for a patient to be included in the study, the patient must meet all the following criteria:
1. Signed, written informed consent in accordance with federal, local, and institutional guidelines
2. Patients age = 60 years with relapsed/refractory AML (defined using WHO criteria) of any type except for acute promyelocytic leukemia (APL; AML M3), after at least one prior AML therapy, who have never undergone and who are not currently eligible for stem cell transplantation, and are currently deemed unfit for intensive chemotherapy.
3. Eastern Cooperative Oncology Group (ECOG) performance status of = 2.
4. Diagnosis of AML (WHO classification definition of = 20% blasts) with the exception of acute promyelocytic leukemia (APL; AML M3); patients must have available archival or recently acquired bone marrow biopsy/aspiration or tumor tissue for central review to be eligible.
5. Relapsed or refractory AML, defined as either:
i) recurrence of disease after a complete remission (CR), or
ii) failure to achieve CR with initial therapy.
6. All patients must have received at least one prior line of AML therapy given at standard doses and must have progressed after their most recent therapy. Prior therapy must have included an adequate trial of a hypomethylating agent with at least 2 cycles.
7. A period of at least 2 weeks must have elapsed since the last anti-leukemia treatment (with the exception of hydroxyurea) before first dose in this study.
8. Objective, documented evidence of disease progression or failure to respond to a reasonable trial of their most recent previous therapy prior to study entry.
9. Serum biochemical values with the following limits unless due to leukemia: creatinine clearance > 30 cc/min calculated using the Cockcroft and Gault (Cockcroft and Gault 1976) formula or measured; total bilirubin = 2 x upper limit of normal (ULN) (except patients with Gilbert’s syndrome [hereditary indirect hyperbilirubinemia] who must have a total bilirubin of = 3 x ULN); transaminases (AST and ALT) = 2.5 x ULN (except patients with known liver involvement of their AML who must have an AST and ALT = 5 x ULN).
10. Coagulation time (Prothrombin time [PT] and partial thromboplastin time [PTT]) = 1.5 x ULN (PTT elevation for known lupus anticoagulant is allowed). Coagulation may also be measured using thromboplastin time (Quick test) if measurement of PT/PTT is not feasible.
11. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other study procedures.
12. Male patients with partners of childbearing potential must agree to use effective contraception during the study period and a period of 3 months after the last dose of study drug.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 75
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 265

Exclusion Criteria

A patient will not be included in the study if any of the following criteria are met:
1. Treatment with any investigational agent within three weeks prior to first dose in this study.
2. Presence of central nervous system (CNS) leukemia.
3. Patients with AML M3 or who are in blast transformation of chronic myeloid leukemia (CML). Prior myelodysplastic syndrome (MDS) is acceptable; prior treatment for MDS does not count as an AML therapy.
4. Patients whose AML is classified as favorable according to the European LeukemiaNet (ELN) disease risk assessment (Appendix 1).
5. Major surgery within 2 weeks of first dose of study drug. Patients must have recovered from the effects of any surgery performed greater than 2 weeks previously.
6. Patient has a concurrent active malignancy.
7. Unstable cardiovascular function:
•symptomatic ischemia, or
•uncontrolled clinically significant conduction abnormalities (i.e., ventricular tachycardia on antiarrhythmic agents are excluded; 1st degree atrioventricular (AV) block or asymptomatic left anterior fascicular block/right bundle branch block (LAFB/RBBB) will not be excluded), or
•congestive heart failure (CHF) NYHA Class = 3, or
•myocardial infarction (MI) within 3 months.
8. Uncontrolled infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose. Infections controlled on concurrent anti-microbial agents are acceptable, and anti-microbial prophylaxis per institutional guidelines are acceptable.
9. Known active hepatitis B virus (HBV) or C virus (HCV) infection; or known to be positive for HCV ribonucleic acid (RNA) or HBsAg (HBV surface antigen).
10. Known human immunodeficiency virus (HIV) infection.
11. Any medical condition which, in the investigator's opinion, could compromise the patient's safety.
12. Patients unable to swallow tablets, or patients with malabsorption syndrome, or any other disease significantly affecting gastrointestinal function