Acute Myeloid LeukemiaPhase 1NCT02485535
Selinexor in Treating Patients With Intermediate- and High-Risk Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome After Transplant
A Phase 1 study testing Laboratory Biomarker Analysis and Selinexor in people with Acute Myeloid Leukemia and de Novo Myelodysplastic Syndrome, run by University of Chicago at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Acute Myeloid Leukemia, de Novo Myelodysplastic Syndrome, Myelodysplastic Syndrome
- What is being tested?
- Laboratory Biomarker Analysis and Selinexor
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Sep 2015to Jul 2020
- 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 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
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- 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
Who cannot join
- 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
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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 (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
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 Study to Assess the Tolerability and Efficacy of Selinexor (KPT-330) as Single Agent to Eliminate Minimal Residual Disease and Maintain Remission in Patients With AML and High Risk MDS After Allogeneic Stem Cell Transplantation
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.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the maximum tolerated dose (MTD) of selinexor in patients with hematologic malignancies, especially acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS), after allogeneic (allo)-stem cell transplant (SCT).
SECONDARY OBJECTIVES:
- To evaluate the toxicities of selinexor as maintenance treatment after allo-SCT.
II. To determine the incidence of non-relapse mortality. III. To determine 2 years post SCT progression-free survival (PFS) and overall survival rates.
IV. To determine the incidence of acute and chronic graft-versus-host disease (GVHD).
- To assess lymphoid and myeloid chimerism post transplantation.
TERTIARY OBJECTIVES:
- To analyze donor immune re-constitution after allo-SCT with selinexor maintenance.
II. To monitor minimal residual disease (MRD) by Wilms tumor 1 (WT1) polymerase chain reaction (PCR) during selinexor treatment in AML/MDS patients.
III. To characterize the physiopathology of the leukemia initiating cells (LIC) at the time of disease relapse on selinexor maintenance and compare that at initial diagnosis of the disease.
OUTLINE: This is a dose-escalation study.
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 orally (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.
After completion of study treatment, patients are followed up for 1 year.
- Conditions
- Acute Myeloid Leukemia, de Novo Myelodysplastic Syndrome, Myelodysplastic Syndrome, Secondary Acute Myeloid Leukemia, Secondary Myelodysplastic Syndrome
- Being tested
- Laboratory Biomarker Analysis, Selinexor
- Medical subject headings
- Leukemia, Myeloid, Acute, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Laboratory Biomarker AnalysisOther
Correlative studies
SelinexorDrug
Also called CRM1 Nuclear Export Inhibitor KPT-330, KPT-330, Selective Inhibitor of Nuclear Export KPT-330, SINE KPT-330
Given PO
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Other: Laboratory Biomarker Analysis; Drug: Selinexor |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Up to 29 days
Secondary outcomes (7)
Incidence of acute GVHD
Summary tabulations of the number and percentage of patients within each category (with a category for missing data) of the parameter will be presented, as well as two-sided 95% CIs.
Measured: Up to 2 years
Incidence of adverse events (AEs), graded according to NCI CTCAE version 4.03
AEs will be summarized by patient incidence rates, therefore, in any tabulation, a patient contributes only once to the count for a given AE. The number and percentage of patients with any treatment emergent AE (TEAE) will be summarized for each treatment group, classified by system organ class and preferred term. The number and percentage of patients with TEAEs assessed by the investigator as at least possibly related to treatment will also be tabulated. The number and percentage of patients with any grade >= 3 TEAE will be tabulated in the same manner. Serious adverse events also tabulated.
Measured: Up to 2 years
Incidence of chronic GVHD
Summary tabulations of the number and percentage of patients within each category (with a category for missing data) of the parameter will be presented, as well as two-sided 95% CIs.
Measured: Up to 2 years
Incidence of non-relapse mortality
Summary tabulations of the number and percentage of patients within each category (with a category for missing data) of the parameter will be presented, as well as two-sided 95% confidence intervals (CIs).
Measured: Up to 2 years
Lymphoid and myeloid chimerism post transplantation
Measured: Up to 2 years
Overall survival (OS)
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. Additional exploratory Cox models may be used to determine the effect of other prognostic factors, such as MRD status at the time of treatment.
Measured: From the date of allo-SCT to the date of disease relapse or death, assessed up to 2 years
PFS
The median duration of 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% CIs on the median and other percentiles, and proportion of censored data. Kaplan-Meier survival rates will also be calculated. Additional exploratory Cox models may be used to determine the effect of other prognostic factors, such as MRD status at the time of treatment.
Measured: From the date of allo-SCT to the date of disease relapse or death, assessed up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jun 2015 (estimated)
- Study start4 Sep 2015
- Primary completion28 Feb 2018
- Study completionJul 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- 12 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
- NCT02485535
- Sponsor's protocol ID
- IRB14-1426
- Other IDs
- NCI-2015-00997, IRB14-1426, P30CA014599
- Status last verified
- May 2021
- First submitted
- 25 Jun 2015
- Last updated
- 13 May 2021
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study to Assess the Tolerability and Efficacy of Selinexor (KPT-330) as Single Agent to Eliminate Minimal Residual Disease and Maintain Remission in Patients With AML and High Risk MDS After Allogeneic Stem Cell Transplantation
- ClinicalTrials.gov ID
- NCT02485535
- Acronym / sponsor ID
- IRB14-1426
- Conditions
- Acute Myeloid Leukemia, de Novo Myelodysplastic Syndrome, Myelodysplastic Syndrome, Secondary Acute Myeloid Leukemia, Secondary Myelodysplastic Syndrome
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- University of ChicagoUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 4 Sep 2015 (actual)
- Primary completion
- 28 Feb 2018 (actual)
- Study completion
- Jul 2020 (actual)
- First posted
- 30 Jun 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 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.
Detailed description
PRIMARY OBJECTIVES:
- To determine the maximum tolerated dose (MTD) of selinexor in patients with hematologic malignancies, especially acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS), after allogeneic (allo)-stem cell transplant (SCT).
SECONDARY OBJECTIVES:
- To evaluate the toxicities of selinexor as maintenance treatment after allo-SCT.
II. To determine the incidence of non-relapse mortality. III. To determine 2 years post SCT progression-free survival (PFS) and overall survival rates.
IV. To determine the incidence of acute and chronic graft-versus-host disease (GVHD).
- To assess lymphoid and myeloid chimerism post transplantation.
TERTIARY OBJECTIVES:
- To analyze donor immune re-constitution after allo-SCT with selinexor maintenance.
II. To monitor minimal residual disease (MRD) by Wilms tumor 1 (WT1) polymerase chain reaction (PCR) during selinexor treatment in AML/MDS patients.
III. To characterize the physiopathology of the leukemia initiating cells (LIC) at the time of disease relapse on selinexor maintenance and compare that at initial diagnosis of the disease.
OUTLINE: This is a dose-escalation study.
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 orally (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.
After completion of study treatment, patients are followed up for 1 year.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (selinexor) | Experimental | Other: Laboratory Biomarker Analysis, Drug: SelinexorBeginning 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. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (14 listed)
- 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:
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 |
|---|---|---|
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (selinexor) |
| SelinexorAlso: CRM1 Nuclear Export Inhibitor KPT-330, KPT-330, Selective Inhibitor of Nuclear Export KPT-330, SINE KPT-330Given PO | Drug | Treatment (selinexor) |
Primary outcome
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
Time frame: Up to 29 days
7 secondary outcomes
Incidence of acute GVHD
Time frame: Up to 2 years
Incidence of adverse events (AEs), graded according to NCI CTCAE version 4.03
Time frame: Up to 2 years
Incidence of chronic GVHD
Time frame: Up to 2 years
Incidence of non-relapse mortality
Time frame: Up to 2 years
Lymphoid and myeloid chimerism post transplantation
Time frame: Up to 2 years
Overall survival (OS)
Time frame: From the date of allo-SCT to the date of disease relapse or death, assessed up to 2 years
PFS
Time frame: From the date of allo-SCT to the date of disease relapse or death, assessed up to 2 years
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 13 May 2021.
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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 Laboratory Biomarker Analysis and Selinexor in people with Acute Myeloid Leukemia and de Novo Myelodysplastic Syndrome, 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 12 inclusion and 14 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 13 May 2021. 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, determined according to incidence of DLT as graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 (time frame: Up to 29 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 May 2021.