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Selinexor With Combination Chemotherapy in Treating Patients With Acute Myeloid Leukemia

Primary Purpose

Acute Myeloid Leukemia

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Cytarabine
Mitoxantrone Hydrochloride
Selinexor
Sponsored by
University of Chicago
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Chicago Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

selinexor, cytarabine, and mitoxantrone

Arm Description

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Allo-SCT success rate
Incidence of adverse events graded according to NCI CTCAE version 4.03
Incidence of non-relapse mortality
Overall survival (OS) rates
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.
Progression-free survival (PFS) rates
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.

Full Information

First Posted
October 5, 2015
Last Updated
April 6, 2020
Sponsor
University of Chicago
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT02573363
Brief Title
Selinexor With Combination Chemotherapy in Treating Patients With Acute Myeloid Leukemia
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)
Study Type
Interventional

2. Study Status

Record Verification Date
April 2020
Overall Recruitment Status
Completed
Study Start Date
October 7, 2015 (Actual)
Primary Completion Date
January 1, 2018 (Actual)
Study Completion Date
May 3, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Chicago
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Actual)

8. Arms, Groups, and Interventions

Arm Title
selinexor, cytarabine, and mitoxantrone
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Cytarabine
Other Intervention Name(s)
Ara-C
Intervention Description
Given per standard of care
Intervention Type
Drug
Intervention Name(s)
Mitoxantrone Hydrochloride
Other Intervention Name(s)
Mitroxone
Intervention Description
Given per standard of care
Intervention Type
Drug
Intervention Name(s)
Selinexor
Other Intervention Name(s)
KPT-330
Intervention Description
Given PO
Primary Outcome Measure Information:
Title
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 Measure Information:
Title
Allo-SCT success rate
Time Frame
After completion of induction therapy (6 months to a year)
Title
Incidence of adverse events graded according to NCI CTCAE version 4.03
Time Frame
Up to 30 days post-treatment
Title
Incidence of non-relapse mortality
Time Frame
Up to 1 year
Title
Overall survival (OS) rates
Description
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.
Time Frame
Date induction chemotherapy to the date of disease relapse or death, assessed up to 1 year
Title
Progression-free survival (PFS) rates
Description
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.
Time Frame
Date induction chemotherapy to the date of disease relapse or death, assessed up to 1 year
Other Pre-specified Outcome Measures:
Title
MRD status as measured by WT1 transcript levels using quantitative real time-PCR
Description
Cox models may be used to determine MRD status during the treatment course.
Time Frame
Up to 1 year

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hongtao Liu
Organizational Affiliation
University of Chicago Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Chicago Comprehensive Cancer Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
29304833
Citation
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.
Results Reference
derived

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Selinexor With Combination Chemotherapy in Treating Patients With Acute Myeloid Leukemia

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