Acute Myeloid LeukemiaPhase 1NCT02573363
Selinexor With Combination Chemotherapy in Treating Patients With Acute Myeloid Leukemia
A Phase 1 study testing Cytarabine, Mitoxantrone Hydrochloride and Selinexor in people with Acute Myeloid Leukemia, run by University of Chicago at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Acute Myeloid Leukemia
- What is being tested?
- Cytarabine, Mitoxantrone Hydrochloride and Selinexor
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Oct 2015to 3 May 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637
About this study
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)
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.
- Conditions
- Acute Myeloid Leukemia
- Being tested
- Cytarabine, Mitoxantrone Hydrochloride, Selinexor
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CytarabineDrug
Also called Ara-C
Given per standard of care
Mitoxantrone HydrochlorideDrug
Also called Mitroxone
Given per standard of care
SelinexorDrug
Also called KPT-330
Given PO
| Study group | Role | What they receive |
|---|---|---|
| selinexor, cytarabine, and mitoxantrone | Experimental | 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. Receives: Drug: Cytarabine; Drug: Mitoxantrone Hydrochloride; Drug: Selinexor |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 56 days
Secondary outcomes (5)
Allo-SCT success rate
Measured: After completion of induction therapy (6 months to a year)
Incidence of adverse events graded according to NCI CTCAE version 4.03
Measured: Up to 30 days post-treatment
Incidence of non-relapse mortality
Measured: Up to 1 year
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.
Measured: Date induction chemotherapy to the date of disease relapse or death, assessed up to 1 year
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.
Measured: Date induction chemotherapy to the date of disease relapse or death, assessed up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Oct 2015 (estimated)
- Study start7 Oct 2015
- Primary completion1 Jan 2018
- Study completion3 May 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- More trials run by University of ChicagoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Chicago
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Hongtao Liu, Principal investigator, University of Chicago Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02573363
- Sponsor's protocol ID
- IRB15-0412
- Other IDs
- NCI-2015-01647, IRB15-0412, P30CA014599
- Status last verified
- Apr 2020
- First submitted
- 5 Oct 2015
- Last updated
- 8 Apr 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 29304833
Study at a glance
From the registry record, last updated by the sponsor on 8 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT02573363
- Acronym / sponsor ID
- IRB15-0412
- Conditions
- Acute Myeloid Leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- University of ChicagoUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 7 Oct 2015 (actual)
- Primary completion
- 1 Jan 2018 (actual)
- Study completion
- 3 May 2019 (actual)
- First posted
- 9 Oct 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| selinexor, cytarabine, and mitoxantrone | Experimental | Drug: Cytarabine, Drug: Mitoxantrone Hydrochloride, Drug: SelinexorINDUCTION 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. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (15 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CytarabineAlso: Ara-CGiven per standard of care | Drug | selinexor, cytarabine, and mitoxantrone |
| Mitoxantrone HydrochlorideAlso: MitroxoneGiven per standard of care | Drug | selinexor, cytarabine, and mitoxantrone |
| SelinexorAlso: KPT-330Given PO | Drug | selinexor, cytarabine, and mitoxantrone |
Primary outcome
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
5 secondary outcomes
Allo-SCT success rate
Time frame: After completion of induction therapy (6 months to a year)
Incidence of adverse events graded according to NCI CTCAE version 4.03
Time frame: Up to 30 days post-treatment
Incidence of non-relapse mortality
Time frame: Up to 1 year
Overall survival (OS) rates
Time frame: Date induction chemotherapy to the date of disease relapse or death, assessed up to 1 year
Progression-free survival (PFS) rates
Time frame: Date induction chemotherapy to the date of disease relapse or death, assessed up to 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Apr 2020.
- Derived from this study: PubMed 29304833Wang 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hongtao Liu principal investigator
University of Chicago Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Cytarabine, Mitoxantrone Hydrochloride and Selinexor in people with Acute Myeloid Leukemia, run by University of Chicago at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02573363, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Apr 2020.