LeukemiaPhase 1NCT02403310
A Study of Selinexor in Combination With Daunorubicin and Cytarabine for Untreated AML
A Phase 1 study testing Selinexor, Daunorubicin and Cytarabine in people with Leukemia and Acute Myeloid Leukemia, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.
Trial summary
The main purpose of this study is to determine the safety of combining selinexor with daunorubicin and cytarabine. The maximal tolerated dose (MTD) of selinexor with daunorubicin and cytarabine will also be established. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leukemia, Acute Myeloid Leukemia, AML
- What is being tested?
- Selinexor, Daunorubicin and Cytarabine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Jun 2015to 1 Feb 2021
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Potential participants must have newly diagnosed, previously untreated acute myeloid leukemia (AML) (excluding M3); Must have adverse-risk AML defined as poor-risk karyotype (complex, monosomal or other known poor risk cytogenetic abnormality), poor-risk mutations/fusion genes or known history of antecedent hematologic disorder, or treatment related AML, or be ≥60 years of age; Cytogenetics, FISH or mutational analysis confirming adverse risk features must have been done within 90 days prior to enrollment.
- May not have undergone any prior therapy for their AML other than hydroxyurea. However, if patients had an antecedent myelodysplastic syndrome (MDS), prior treatment with a hypomethylating agent or any other therapy (with the exception of allogeneic stem cell transplant) used to treat their MDS is allowed.
- Age ≥18 years
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- Life expectancy of greater than 2 months
- Must have normal organ function
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- Able and willing to adhere to the study visit schedule and other protocol requirements
- Baseline left ventricular ejection fraction (LVEF) ≥ 50%
- Women of child-bearing potential must have a negative serum or urine pregnancy test with a sensitivity of at least 50 milli-international units per milliliter (mIU)mL) within 10 days and again within 24 hours prior to beginning study treatment. Participants of childbearing potential must practice recommended contraception. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Breastfeeding mothers must agree to discontinue nursing if the mother is treated with selinexor.
- Ability to understand and the willingness to sign a written informed consent document
- Able to swallow capsules and have no evidence of GI tract abnormality that would alter the absorption of oral medications
- Prothrombin time (PT) and partial thromboplastin time (PTT) ≤ 1.5 x upper limit of normal (ULN)
Who cannot join
- May not be receiving any other investigational agents
- Documented central nervous system (CNS) involvement of AML
- AML with favorable risk cytogenetic abnormalities including t(15;17), t(8;21) or inv(16)
- Potential participants who are in the blast phase of chronic myeloid leukemia
- Major surgery within 2 weeks of first dose of study drug; must have recovered from the effects of any surgery performed greater than 2 weeks prior
- White blood cell (WBC) count ≥50,000 on hydroxyurea
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- Predicted inability to tolerate standard induction chemotherapy with daunorubicin and cytarabine
- Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- HIV-positive, receiving combination anti-retroviral therapy
- No other malignancies in addition to AML that are currently requiring treatment with the exception of basal cell or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix or breast
- History of allogeneic stem cell transplant for MDS or any other antecedent hematologic disorder.
Trial locations and contacts
1 site in 1 country.
United States1 site
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, 33612
About this study
Official title: A Phase 1 Investigator Sponsored Study of Selinexor in Combination With Daunorubicin and Cytarabine in Patients With Previously Untreated Poor-Risk Acute Myeloid Leukemia
The main purpose of this study is to determine the safety of combining selinexor with daunorubicin and cytarabine. The maximal tolerated dose (MTD) of selinexor with daunorubicin and cytarabine will also be established.
Read the detailed description
Induction Therapy - Dose escalation of selinexor with Daunorubicin and cytarabine at fixed doses.
Consolidation Phase - Patients who are in complete remission (CR) or complete remission with incomplete count recovery (CRi) by day ≤70 and have recovered from any previous non- hematologic toxicity to baseline or grade ≤1 by day ≤70 following induction chemotherapy may go on to receive consolidation therapy for up to 2 cycles. The consolidation treatment phase will include up to two courses of therapy (28 day cycles) as follows:
Daunorubicin 45mg/m^2/day (days 1-2) Cytarabine 100mg/m^2/day (continuous infusion on days 1-5) Selinexor same dose as induction (days 1,3,8,10) unless dose limiting toxicity (DLT) dictates a dose reduction. Selinexor will be given 2 hours prior to daunorubicin on day 1.
A second cycle of consolidation therapy using the same doses as above will be administered, at the investigators discretion, between 28 and 42 days following initiation of the first consolidation treatment, after peripheral blood counts have recovered to CR, CRi levels, and after recovery from any non-hematologic toxicity to baseline or grade ≤1. Dose escalation of Selinexor will not occur during the consolidation phase.
Maintenance Phase - Patients who remain in CR, CRi after up to 2 cycles of consolidation and are not eligible for allogeneic stem cell transplant will be eligible for the maintenance phase of treatment after recovery from any previous non-hematologic toxicity to baseline or grade ≤1. Maintenance therapy will consist of:
Selinexor at the same dose as induction on days 1 and 8 of a 21 day cycle. They will continue for a maximum of 12 months.
Expansion Phase - Once the MTD has been established, there will be an expansion phase to enroll an additional 13 subjects at the MTD to better characterize the safety profile and tolerability.
- Conditions
- Leukemia, Acute Myeloid Leukemia, AML
- Being tested
- Selinexor, Daunorubicin, Cytarabine
- Keywords
- adverse-risk AML, poor-risk karyotype, cytogenetic abnormality, poor-risk mutations, antecedent hematologic disorder, treatment related AML
- Medical subject headings
- Leukemia, Leukemia, Myeloid, Acute, Chromosome Aberrations
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SelinexorDrug
Also called KPT-330, SINE KPT-330
Induction: Oral selinexor on days 1, 3, 8, 10, 15 and 17.
- Dose Level 2: 80 mg twice weekly.
- Dose Level 1 (starting dose): 60 mg twice weekly.
- Dose Level -1: 40 mg twice weekly.
Consolidation: Selinexor same dose as induction (days 1,3,8,10) unless dose limiting toxicity (DLT) dictates a dose reduction.
Maintenance: Selinexor at the same dose as induction on days 1 and 8 a 21 day cycle. They will continue for a maximum of 12 months.
DaunorubicinDrug
Also called Cerubidine®, daunomycin cerubidine, daunorubicin hydrochloride
Induction: Daunorubicin 60 mg/m^2/day (days 1-3).
Consolidation: Daunorubicin 45 mg/m^2/day (days 1-2).
CytarabineDrug
Also called Cytosar-U, Tarabine PFS, ARA-C
Induction: Cytarabine 100 mg/m^2/day (days 1-7).
Consolidation: Cytarabine 100 mg/m^2/day (continuous infusion on days 1-5).
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation - Selinexor | Experimental | Dose escalation of selinexor with fixed doses of daunorubicin and cytarabine.
Induction Therapy may be followed by Consolidation Phase and Maintenance Phase as outlined in the Detailed Description and Intervention Descriptions. Receives: Drug: Selinexor; Drug: Daunorubicin; Drug: Cytarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximal Tolerated Dose (MTD) of Selinexor
MTD / Recommended Phase II Dose (RP2D) of selinexor with daunorubicin and cytarabine. Dose Limiting Toxicity (DLT): Non-hematologic - Any grade 3-4 drug-related non-hematologic toxicity, with the following exceptions: Nausea/vomiting or diarrhea adequately controlled with antiemetics/antidiarrheals; Infection or febrile neutropenia adequately controlled with antibiotics; Liver function abnormalities (without clinical symptoms) that recover to baseline or grade 0-1 within 7 days; Grade 3-4 electrolyte or metabolic laboratory abnormalities that are not considered clinically significant by the treating investigator/physician and that recover to baseline or grade 0-1 within 7 days; Alopecia. Hematologic - Grade 3-4 neutropenia and/or thrombocytopenia (thought to be due to marrow hypoplasia and NOT leukemic burden) that does not recover to grade ≤2 by day 56.
Measured: Up to 18 months
Secondary outcomes (4)
Rate of Complete Response (CR) Plus Complete Response with Incomplete Count Recovery (CRi).
A CR designation requires that the patient achieve the morphologic leukemia-free state and have an absolute neutrophil count of more than 1,000/μL and platelets of 100,000/μL. A CRi designation requires that the patient achieve the morphologic leukemia-free state with incomplete recovery of neutrophils (<1,000/μL) or platelets (<100,000/μL).
Measured: Up to 18 months
Disease Free Survival (DFS)
Disease free survival is measured from the time measurement criteria are met for CR/CRi until the first date that relapse is objectively documented.
Measured: Up to 18 months
Time to Progression (TTP)
Time to progression is a secondary endpoint that will be measured as the time from when the patient started treatment to the time the patient is first recorded as having relapsed, or the date of death if the patient dies due to causes other than disease progression.
Measured: Up to 18 months
Overall Survival (OS)
Overall survival is a secondary endpoint that will be measured as time from the start of treatment until death from any cause, or the last date the patient was known to be alive.
Measured: Up to 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Mar 2015 (estimated)
- Study start18 Jun 2015
- Primary completion13 Sep 2016
- Study completion1 Feb 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- More trials run by H. Lee Moffitt Cancer Center and Research InstituteThe 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
- 21 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Karyopharm Therapeutics Inc
- Responsible party
- Sponsor
- Investigators
- Kendra Sweet, M.D., Principal investigator, H. Lee Moffitt Cancer Center and Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02403310
- Sponsor's protocol ID
- MCC-18157
- Status last verified
- Sep 2022
- First submitted
- 26 Mar 2015
- Last updated
- 3 Oct 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Investigator Sponsored Study of Selinexor in Combination With Daunorubicin and Cytarabine in Patients With Previously Untreated Poor-Risk Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT02403310
- Acronym / sponsor ID
- MCC-18157
- Conditions
- Leukemia, Acute Myeloid Leukemia, AML
- Keywords
- adverse-risk AML, poor-risk karyotype, cytogenetic abnormality, poor-risk mutations, antecedent hematologic disorder, treatment related AML
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- H. Lee Moffitt Cancer Center and Research InstituteUniversity, hospital or other
- Collaborators
- Karyopharm Therapeutics Inc
- Study start
- 18 Jun 2015 (actual)
- Primary completion
- 13 Sep 2016 (actual)
- Study completion
- 1 Feb 2021 (actual)
- First posted
- 31 Mar 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.
The main purpose of this study is to determine the safety of combining selinexor with daunorubicin and cytarabine. The maximal tolerated dose (MTD) of selinexor with daunorubicin and cytarabine will also be established.
Detailed description
Induction Therapy - Dose escalation of selinexor with Daunorubicin and cytarabine at fixed doses.
Consolidation Phase - Patients who are in complete remission (CR) or complete remission with incomplete count recovery (CRi) by day ≤70 and have recovered from any previous non- hematologic toxicity to baseline or grade ≤1 by day ≤70 following induction chemotherapy may go on to receive consolidation therapy for up to 2 cycles. The consolidation treatment phase will include up to two courses of therapy (28 day cycles) as follows:
Daunorubicin 45mg/m^2/day (days 1-2) Cytarabine 100mg/m^2/day (continuous infusion on days 1-5) Selinexor same dose as induction (days 1,3,8,10) unless dose limiting toxicity (DLT) dictates a dose reduction. Selinexor will be given 2 hours prior to daunorubicin on day 1.
A second cycle of consolidation therapy using the same doses as above will be administered, at the investigators discretion, between 28 and 42 days following initiation of the first consolidation treatment, after peripheral blood counts have recovered to CR, CRi levels, and after recovery from any non-hematologic toxicity to baseline or grade ≤1. Dose escalation of Selinexor will not occur during the consolidation phase.
Maintenance Phase - Patients who remain in CR, CRi after up to 2 cycles of consolidation and are not eligible for allogeneic stem cell transplant will be eligible for the maintenance phase of treatment after recovery from any previous non-hematologic toxicity to baseline or grade ≤1. Maintenance therapy will consist of:
Selinexor at the same dose as induction on days 1 and 8 of a 21 day cycle. They will continue for a maximum of 12 months.
Expansion Phase - Once the MTD has been established, there will be an expansion phase to enroll an additional 13 subjects at the MTD to better characterize the safety profile and tolerability.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation - Selinexor | Experimental | Drug: Selinexor, Drug: Daunorubicin, Drug: CytarabineDose escalation of selinexor with fixed doses of daunorubicin and cytarabine. Induction Therapy may be followed by Consolidation Phase and Maintenance Phase as outlined in the Detailed Description and Intervention Descriptions. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Potential participants must have newly diagnosed, previously untreated acute myeloid leukemia (AML) (excluding M3); Must have adverse-risk AML defined as poor-risk karyotype (complex, monosomal or other known poor risk cytogenetic abnormality), poor-risk mutations/fusion genes or known history of antecedent hematologic disorder, or treatment related AML, or be ≥60 years of age; Cytogenetics, FISH or mutational analysis confirming adverse risk features must have been done within 90 days prior to enrollment.
- May not have undergone any prior therapy for their AML other than hydroxyurea. However, if patients had an antecedent myelodysplastic syndrome (MDS), prior treatment with a hypomethylating agent or any other therapy (with the exception of allogeneic stem cell transplant) used to treat their MDS is allowed.
- Age ≥18 years
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- Life expectancy of greater than 2 months
Key exclusion criteria (11 listed)
- May not be receiving any other investigational agents
- Documented central nervous system (CNS) involvement of AML
- AML with favorable risk cytogenetic abnormalities including t(15;17), t(8;21) or inv(16)
- Potential participants who are in the blast phase of chronic myeloid leukemia
- Major surgery within 2 weeks of first dose of study drug; must have recovered from the effects of any surgery performed greater than 2 weeks prior
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 |
|---|---|---|
| SelinexorAlso: KPT-330, SINE KPT-330Induction: Oral selinexor on days 1, 3, 8, 10, 15 and 17. * Dose Level 2: 80 mg twice weekly. * Dose Level 1 (starting dose): 60 mg twice weekly. * Dose Level -1: 40 mg twice weekly. Consolidation: Selinexor same dose as induction (days 1,3,8,10) unless dose limiting toxicity (DLT) dictates a dose reduction. Maintenance: Selinexor at the same dose as induction on days 1 and 8 a 21 day cycle. They will continue for a maximum of 12 months. | Drug | Dose Escalation - Selinexor |
| DaunorubicinAlso: Cerubidine®, daunomycin cerubidine, daunorubicin hydrochlorideInduction: Daunorubicin 60 mg/m^2/day (days 1-3). Consolidation: Daunorubicin 45 mg/m^2/day (days 1-2). | Drug | Dose Escalation - Selinexor |
| CytarabineAlso: Cytosar-U, Tarabine PFS, ARA-CInduction: Cytarabine 100 mg/m^2/day (days 1-7). Consolidation: Cytarabine 100 mg/m^2/day (continuous infusion on days 1-5). | Drug | Dose Escalation - Selinexor |
Primary outcome
Maximal Tolerated Dose (MTD) of Selinexor
Time frame: Up to 18 months
MTD / Recommended Phase II Dose (RP2D) of selinexor with daunorubicin and cytarabine. Dose Limiting Toxicity (DLT): Non-hematologic - Any grade 3-4 drug-related non-hematologic toxicity, with the following exceptions: Nausea/vomiting or diarrhea adequately controlled with antiemetics/antidiarrheals; Infection or febrile neutropenia adequately controlled with antibiotics; Liver function abnormalities (without clinical symptoms) that recover to baseline or grade 0-1 within 7 days; Grade 3-4 electrolyte or metabolic laboratory abnormalities that are not considered clinically significant by the treating investigator/physician and that recover to baseline or grade 0-1 within 7 days; Alopecia. Hematologic - Grade 3-4 neutropenia and/or thrombocytopenia (thought to be due to marrow hypoplasia and NOT leukemic burden) that does not recover to grade ≤2 by day 56.
4 secondary outcomes
Rate of Complete Response (CR) Plus Complete Response with Incomplete Count Recovery (CRi).
Time frame: Up to 18 months
Disease Free Survival (DFS)
Time frame: Up to 18 months
Time to Progression (TTP)
Time frame: Up to 18 months
Overall Survival (OS)
Time frame: Up to 18 months
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 3 Oct 2022.
- Moffitt Cancer Center Clinical Trials websiteLink provided by the sponsor.
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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.
Kendra Sweet, M.D. principal investigator
H. Lee Moffitt Cancer Center and Research Institute
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 Selinexor, Daunorubicin and Cytarabine in people with Leukemia and Acute Myeloid Leukemia, run by H. Lee Moffitt Cancer Center and Research Institute 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 11 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 3 Oct 2022. 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?
Maximal Tolerated Dose (MTD) of Selinexor (time frame: Up to 18 months). 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 3 Oct 2022.