Selinexor With Combination Chemotherapy in Treating Patients With Acute Myeloid Leukemia
Phase I Investigator Sponsored Study to Assess the Tolerability and Efficacy of Selinexor in Combination With High Dose Cytarabine (HiDAC) and Mitoxantrone Chemotherapy for Remission Induction in Acute Myelogenous Leukemia (AML)
3 other identifiers
interventional
25
1 country
1
Brief Summary
This phase I trial studies the side effects and the best dose of selinexor when give together with standard chemotherapy, high dose cytarabine and mitoxantrone hydrochloride, in treating patients with acute myeloid leukemia. Selinexor may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cytarabine and mitoxantrone hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving selinexor together with standard chemotherapy may be a better treatment for patients with acute myeloid leukemia.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Oct 2015
Typical duration for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 5, 2015
CompletedStudy Start
First participant enrolled
October 7, 2015
CompletedFirst Posted
Study publicly available on registry
October 9, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
May 3, 2019
CompletedApril 8, 2020
April 1, 2020
2.2 years
October 5, 2015
April 6, 2020
Conditions
Outcome Measures
Primary Outcomes (1)
MTD of selinexor based on the dose-limiting toxicity graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03
56 days
Secondary Outcomes (5)
Allo-SCT success rate
After completion of induction therapy (6 months to a year)
Incidence of adverse events graded according to NCI CTCAE version 4.03
Up to 30 days post-treatment
Incidence of non-relapse mortality
Up to 1 year
Overall survival (OS) rates
Date induction chemotherapy to the date of disease relapse or death, assessed up to 1 year
Progression-free survival (PFS) rates
Date induction chemotherapy to the date of disease relapse or death, assessed up to 1 year
Other Outcomes (1)
MRD status as measured by WT1 transcript levels using quantitative real time-PCR
Up to 1 year
Study Arms (1)
selinexor, cytarabine, and mitoxantrone
EXPERIMENTALINDUCTION CHEMOTHERAPY: Patients receive high-dose cytarabine and mitoxantrone hydrochloride per standard of care on days 1 and 5, and selinexor PO on days 2, 4, 9, and 11. CONSOLIDATION CHEMOTHERAPY: Patients receive high-dose cytarabine per standard of care on days 1, 3, and 5, and selinexor PO on days 2, 4, 9, and 11. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE CHEMOTHERAPY: Patients achieving at least stable disease after consolidation chemotherapy may receive selinexor PO on days 1, 8, 15, and 22 at the discretion of principal investigator.
Interventions
Given per standard of care
Eligibility Criteria
You may qualify if:
- Signed, written informed consent in accordance with federal, local, and institutional guidelines
- Patients with newly diagnosed or relapsed/refractory AML, except acute promyelocytic leukemia (APL), requiring intensive induction chemotherapy
- Eastern Cooperative Oncology Group (ECOG) performance status of =\< 2
- 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 \[ALT\]) =\< 3.0 x upper limit of normal (ULN) unless due to leukemia infiltration
- 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:
- Treatment with any investigational agent within two weeks prior to first dose in this study; hydroxyurea is allowed to control the AML prior to treatment on the study
- AML central nervous system (CNS) involvement
- 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 advantage 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 \[left anterior fascicular block (LAFB)/right bundle branch block (RBBB)\] will not be excluded), or
- Congestive heart failure (CHF) New York Heart Association (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 is 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
- Seizure or cerebrovascular accident (CVA) in the last year
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Chicagolead
- National Cancer Institute (NCI)collaborator
Study Sites (1)
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637, United States
Related Publications (1)
Wang AY, Weiner H, Green M, Chang H, Fulton N, Larson RA, Odenike O, Artz AS, Bishop MR, Godley LA, Thirman MJ, Kosuri S, Churpek JE, Curran E, Pettit K, Stock W, Liu H. A phase I study of selinexor in combination with high-dose cytarabine and mitoxantrone for remission induction in patients with acute myeloid leukemia. J Hematol Oncol. 2018 Jan 5;11(1):4. doi: 10.1186/s13045-017-0550-8.
PMID: 29304833DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Hongtao Liu
University of Chicago Comprehensive Cancer Center
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
October 5, 2015
First Posted
October 9, 2015
Study Start
October 7, 2015
Primary Completion
January 1, 2018
Study Completion
May 3, 2019
Last Updated
April 8, 2020
Record last verified: 2020-04