Selinexor in Treating Patients With Intermediate- and High-Risk Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome After Transplant

NCT02485535 | Completed Phase 1 DMC

• 3 other identifiers: IRB14-1426NCI-2015-00997P30CA014599
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and best dose of selinexor when given after stem cell transplant in treating patients with acute myeloid leukemia that is at intermediate or high risk of spreading or coming back (intermediate- or high-risk), or myelodysplastic syndrome that is at high risk of spreading or coming back (high-risk). Selinexor works to stop cancer growth by blocking an enzyme, which may cause cancer cells to die and also kill cells that cause the cancer to grow, which commonly do not respond to regular chemotherapy.

Conditions

Acute Myeloid Leukemia; de Novo Myelodysplastic Syndrome; Myelodysplastic Syndrome; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (1)

• MTD of selinexor, determined according to incidence of DLT as graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03

  Up to 29 days

Secondary Outcomes (7)

• Incidence of acute GVHD

  Up to 2 years

• Incidence of adverse events (AEs), graded according to NCI CTCAE version 4.03

  Up to 2 years

• Incidence of chronic GVHD

  Up to 2 years

• Incidence of non-relapse mortality

  Up to 2 years

• Lymphoid and myeloid chimerism post transplantation

  Up to 2 years

Study Arms (1)

Treatment (selinexor)

EXPERIMENTAL

Beginning on day 60-100 after allo-SCT without evidence of GVHD above grade 1 and disease relapse with stable hematopoietic recovery, patients receive selinexor PO on day 1 of each week or on days 1 and 3 of weeks 1-3. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis; Drug: Selinexor

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (selinexor)

Selinexor DRUG

Given PO

Also known as: CRM1 Nuclear Export Inhibitor KPT-330, KPT-330, Selective Inhibitor of Nuclear Export KPT-330, SINE KPT-330

Treatment (selinexor)

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed, written informed consent in accordance with federal, local, and institutional guidelines
• Patients underwent allo-SCT with intermediate risk and high risk AML and high risk MDS (defined by American Society for Blood and Marrow Transplantation \[ASBMT\] criteria), who are within 60 to 100 days after allo-SCT
• There is no evidence of disease relapse at the time of screening, and minimal residual disease (MRD) is acceptable
• Eastern Cooperative Oncology Group (ECOG) performance status of =\< 2
• Absolute neutrophil count (ANC) \> 1000 uL
• Platelets \>= 20,000 without platelet transfusion
• Creatinine clearance \> 30 cc/min calculated using the Cockcroft and Gault (1976) formula or measured
• Total bilirubin =\< 2 mg/dl unless high indirect bilirubin is due to a congenital disorder
• Transaminases (aspartate aminotransferase \[AST\] or alanine aminotransferase \[ALT\]) =\< 2.0 x upper limit of normal (ULN)
• Prothrombin time (PT) and partial thromboplastin time (PTT) =\< 2 x ULN
• Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other study procedures
• It is important patients understand the need to use birth control while on this study; female patients of child-bearing potential must agree to use dual methods of contraception and have a negative serum pregnancy test at screening (\< 3 days prior to first dose), 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; for both male and female patients, effective methods of contraception must be used throughout the study and for three months following the last dose

You may not qualify if:

• Patients with acute GVHD grade II-IV
• Treatment with any investigational agent within three weeks prior to first dose in this study
• 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
• Patient has a concurrent active malignancy under treatment
• 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
• 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
• 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)
• Known human immunodeficiency virus (HIV) infection
• Any medical condition which, in the investigator's opinion, could compromise the patient's safety
• Patients unable to swallow tablets or patients with malabsorption syndrome, or any other disease significantly affecting gastrointestinal function

Sponsors & Collaborators

• University of Chicago: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

selinexor

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Study Officials

• Hongtao Liu

  University of Chicago Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2015
• First Posted: June 30, 2015
• Study Start: September 4, 2015
• Primary Completion: February 28, 2018
• Study Completion: July 1, 2020
• Last Updated: May 13, 2021

Record last verified: 2021-05

Locations

US (1)