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Selinexor With Combination Chemotherapy in Treating Patients With Acute Myeloid Leukemia

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ClinicalTrials.gov Identifier: NCT02573363
Recruitment Status : Active, not recruiting
First Posted : October 9, 2015
Last Update Posted : June 11, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of Chicago

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.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Drug: Cytarabine Drug: Mitoxantrone Hydrochloride Drug: Selinexor Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 25 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : October 7, 2015
Actual Primary Completion Date : January 1, 2018
Estimated Study Completion Date : January 2020


Arm Intervention/treatment
Experimental: selinexor, cytarabine, and mitoxantrone

INDUCTION 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.

Drug: Cytarabine
Given per standard of care
Other Name: Ara-C

Drug: Mitoxantrone Hydrochloride
Given per standard of care
Other Name: Mitroxone

Drug: Selinexor
Given PO
Other Name: KPT-330




Primary Outcome Measures :
  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 [ Time Frame: 56 days ]

Secondary Outcome Measures :
  1. Allo-SCT success rate [ Time Frame: After completion of induction therapy (6 months to a year) ]
  2. Incidence of adverse events graded according to NCI CTCAE version 4.03 [ Time Frame: Up to 30 days post-treatment ]
  3. Incidence of non-relapse mortality [ Time Frame: Up to 1 year ]
  4. Overall survival (OS) rates [ Time Frame: Date induction chemotherapy to the date of disease relapse or death, assessed up to 1 year ]
    The median duration of OS will be estimated based on the 50th percentile of the Kaplan-Meier distribution; additional summary statistics will be presented, including the 25th and 75th percentiles, 95% CIs on the median and other percentiles, and proportion of censored data. Kaplan-Meier survival rates will also be calculated.

  5. Progression-free survival (PFS) rates [ Time Frame: Date induction chemotherapy to the date of disease relapse or death, assessed up to 1 year ]
    PFS will be estimated based on the 50th percentile of the Kaplan-Meier distribution; additional summary statistics will be presented, including the 25th and 75th percentiles, 95% confidence intervals (CIs) on the median and other percentiles, and proportion of censored data. Kaplan-Meier survival rates will also be calculated.


Other Outcome Measures:
  1. MRD status as measured by WT1 transcript levels using quantitative real time-PCR [ Time Frame: Up to 1 year ]
    Cox models may be used to determine MRD status during the treatment course.



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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02573363


Locations
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United States, Illinois
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States, 60637
Sponsors and Collaborators
University of Chicago
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Hongtao Liu University of Chicago Comprehensive Cancer Center

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: University of Chicago
ClinicalTrials.gov Identifier: NCT02573363     History of Changes
Other Study ID Numbers: IRB15-0412
NCI-2015-01647 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
IRB15-0412 ( Other Identifier: University of Chicago Comprehensive Cancer Center )
P30CA014599 ( U.S. NIH Grant/Contract )
First Posted: October 9, 2015    Key Record Dates
Last Update Posted: June 11, 2018
Last Verified: June 2018

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Mitoxantrone
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Cytarabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors