Acute Myeloid Leukemia (Relapsed/Refractory)Phase 2NCT02249091
A Phase II Study of Selinexor Plus Cytarabine and Idarubicin in Patients With Relapsed/Refractory Acute Myeloid Leukemia (AML)
A Phase 2 study testing Selinexor, Idarubicin and Cytarabine in people with Acute Myeloid Leukemia (Relapsed/Refractory), run by GSO Global Clinical Research BV at 3 sites in Germany.
Trial summary
Acute Myeloid Leukemia (AML) is currently treated with chemotherapy by combining several drugs with different ways of inhibiting the cell growth. In this trial, standard chemotherapeutics that have proven their effectiveness for years, Ara-C and Idarubicin, will be combined with a new drug called Selinexor. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia (Relapsed/Refractory)
- What is being tested?
- Selinexor, Idarubicin 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
- 42 participants
- Where
- 3 sitesGermany
- Study dates
- Sep 2014to 31 Jul 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Cytological or histological diagnosis of AML with the exception of promyelocytic leukemia (AML M3)
- Patients must have relapsed/refractory disease (relapse after stem cell transplantation is permitted) as defined as:
- patients with <PR after first cycle of induction chemotherapy, or
- patients with <CR(i) after second cycle of induction chemotherapy, or
- patients who relapse after conventional chemotherapy or
- patients who have undergone a single stem cell transplantation and who have relapse of their AML.
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- Men and women aged ≥18 years and eligible for standard dose of chemotherapy (7+3);
- A period of at least 3 weeks needs to have elapsed since last treatment (with the exception of hydroxyurea) before participating in this study. Hydroxyurea induction therapy to reduce peripheral blast counts is permitted prior to initiation of treatment on protocol. Treatment may begin in <3 weeks from last treatment if deemed in the best interest of the patient after discussion with the PI of the study;
- ECOG performance status ≤ 2
- Serum biochemical values with the following limits unless considered due to leukemia: creatinine ≤2 mg/dl; total bilirubin ≤2x ULN, unless increase is due to hemolysis or congenital disorder; transaminases (SGPT or SGOT) ≤2.5x ULN.
- Ability to swallow and retain oral medication;
- Ability to understand and provide signed informed consent;
- Cardiac ejection fraction must be >/=50% (by echocardiography).
- Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
Who cannot join
- Treatment with any investigational agent within four weeks.
- Cumulative anthracycline dose (daunorubicin or equivalent) >360 mg/m^2
- HIV infection
- Presence of any medical or psychiatric condition which may limit full compliance with the study, including but not limited to:
- Presence of CNS leukemia
- Unresolved toxicity from previous anti-cancer therapy or incomplete recovery from surgery.
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- For patients after SCT as part of prior treatment:
- Necessity of immunosuppressive drugs
- GvHD > grade 1
- Any of the following within the 12 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis, or other thromboembolic event.
- Ongoing cardiac dysrhythmias of NCI CTCAE >/= Grade 2.
- Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study.
- Clinically significant bleeding within 1 month
Trial locations and contacts
3 sites in 1 country.
Germany3 sites
Universitätsklinikum Frankfurt
Frankfurt am Main, Hesse, 60590
Universitätsklinikum Hamburg-Eppendorf
Hamburg, 20246
Medizinische Hochschule Hannover
Hanover, Lower Saxony, 30625
About this study
Official title: An Investigator-Initiated Study To Evaluate Ara-C and Idarubicin in Combination With the Selective Inhibitor Of Nuclear Export (SINE) Selinexor (KPT-330) in Patients With Relapsed Or Refractory AML
Acute Myeloid Leukemia (AML) is currently treated with chemotherapy by combining several drugs with different ways of inhibiting the cell growth. In this trial, standard chemotherapeutics that have proven their effectiveness for years, Ara-C and Idarubicin, will be combined with a new drug called Selinexor.
Selinexor inhibits the growth of cancer cells by keeping certain proteins in the nucleus which control the cell growth.
- Being tested
- Selinexor, Idarubicin, Cytarabine
- Medical subject headings
- Leukemia, Myeloid, Acute, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SelinexorDrug
Also called KPT-330
Patients receive Selinexor as specified in arm/group description (8 doses of 40 mg/m^2 or 6 doses of 60 mg per induction cycle).
IdarubicinDrug
Infusion, iv, 10 mg/m^2, on days 1,3,5 in cycle 1, on days 1,3 in cycle 2
CytarabineDrug
Also called Ara-C
Continuous infusion day 1 to 7, 100 mg/m^2, iv,
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 / Selinexor 40 mg/m^2 in combination with cytarabine and idarubicin | Experimental | All enrolled patients are treated with cytarabine at a dose of 100 mg/m² continuous infusion (day 1-7) and idarubicin at a dose of 10 mg/m^2 iv (day 1,3,5) every 4 weeks and selinexor for up to 2 induction cycles. If a second cycle is applied idarubicin is only given on day 1 and 3.
Selinexor is administered at a dose of 40 mg/m^2 twice weekly orally starting on day 2 (total of 8 doses per induction cycle). Receives: Drug: Selinexor; Drug: Idarubicin; Drug: Cytarabine |
| Cohort 2 / Selinexor 60 mg flat dose in combination with cytarabine and idarubicin | Experimental | All enrolled patients are treated with cytarabine at a dose of 100 mg/m^2 continuous infusion (day 1-7) and idarubicin at a dose of 10 mg/m^2 iv (day 1,3,5) every 4 weeks and selinexor for up to 2 induction cycles. If a second cycle is applied idarubicin is only given on day 1 and 3.
Selinexor is administered at a flat dose of 60 mg twice weekly orally in weeks 1-3 of a 4-week cycle starting on day 2 (total of 6 doses per induction cycle). Receives: Drug: Selinexor; Drug: Idarubicin; Drug: Cytarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With CR/CRi = Overall Reponse Rate
Efficacy of selinexor in combination with standard chemotherapy in patients with relapsed/refractory AML by determination of rate of complete response (CR) or morphologic complete response with incomplete blood count recovery (CRi), as defined by the recommendations on diagnosis and management of AML in adults from an international expert panel, on behalf of the European LeukemiaNet:
CR: Absolute Neutrophil count (ANC) >1.0x10^9/L, Platelet count >100x10^9/L, Bone marrow blasts <5%, no Auer rods, no evidence of extramedullary disease.
CRi: Same as CR, but ANC may be <1.0x10^9/L and/or Platelet count <100x10^9/L.
Patients with morphologic leukemia free-state (MLFS) were included in the group of responders. MLFS: Bone marrow blasts <5%, no Auer rods, no evidence of extramedullary disease.
The best response after Selinexor treatment was analyzed, thus the best response after the induction cycle(s).
Measured: 1-2 induction cycles (4 - 8 weeks)
Secondary outcomes (7)
Number of Participants With Partial Remission (PR) = Rate of PR
Efficacy of selinexor in combination with standard chemotherapy in patients with relapsed/refractory AML by determination of rate of partial remission(PR) as defined by the recommendations on diagnosis and management of AML in adults from an international expert panel, on behalf of the European LeukemiaNet:
PR: Absolute Neutrophil count (ANC) >1.0x10^9/L, Platelet count >100x10^9/L, at least a 50% decrease in the percentage of marrow aspirate blasts to 5-25%, or marrow blasts <5% with persistent Auer rods.
The best response after Selinexor treatment was analyzed, thus the best response after the induction cycle(s).
Measured: 1-2 induction cycles (4 - 8 weeks)
Percentage of Patients Transplanted After Induction Therapy (Stem Cell Transplantation)
Percentage of patients being transplanted after induction therapy (stem cell transplantation)
Measured: 1-2 induction cycles (4 - 8 weeks)
Early Death Rate
Early death was defined as death before the end of the first induction cycle.
Measured: 1 induction cycle (4 weeks)
Overall Survival
Overall survival (OS) was calculated from the date of informed consent to the date of death. Patients still alive at the end of follow-up were censored at the last date of follow-up.
Measured: Time from registration to event, max 2 years
Relapse-Free Survival
Relapse-free survival (RFS) was calculated from the date of CR/CRi until death or relapse, whichever occurred first. Patients were censored on the date of the last follow-up if they were alive without relapse.
Measured: Time from registration to event, max 2 years
Event-Free Survival
Event-free survival (EFS) was calculated from the time of informed consent until death, not achieving CR/CRi or relapse after CR/CRi.
Measured: Time from registration to event, max 2 years
Progression-Free Survival
Progression-free survival (PFS) was calculated from the time of informed consent to the date of recurrence or death, whichever occurred first. Patients were censored at the date of the last follow-up visit if they were alive without relapse.
Disease progression was defined as presence of >50% increase in bone marrow blasts to a level of at least 50% and/or a doubling of the percentage of peripheral blood blasts to a level of at least 50%.
Measured: Time from registration to event, max 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2014 (estimated)
- Study startSep 2014
- Primary completion31 Jul 2018
- Study completion31 Jul 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Acute Myeloid Leukemia (Relapsed/Refractory)Studies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- In the initial protocol, 25 patients are included in the clinical trial on the schedule described as cohort 1. After an amendment 15 further patients are included on the schedule described as cohort 2.
- Masking
- None (open label)
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- GSO Global Clinical Research BV
- Sponsor type
- University, hospital or other
- Collaborators
- Karyopharm Therapeutics Inc
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02249091
- Sponsor's protocol ID
- SAIL
- Other IDs
- 2014-000526-37, 2014
- Status last verified
- Aug 2021
- First submitted
- 16 Sep 2014
- Last updated
- 25 Aug 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Investigator-Initiated Study To Evaluate Ara-C and Idarubicin in Combination With the Selective Inhibitor Of Nuclear Export (SINE) Selinexor (KPT-330) in Patients With Relapsed Or Refractory AML
- ClinicalTrials.gov ID
- NCT02249091
- Acronym / sponsor ID
- SAIL
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- GSO Global Clinical Research BVUniversity, hospital or other
- Collaborators
- Karyopharm Therapeutics Inc
- Study start
- Sep 2014
- Primary completion
- 31 Jul 2018 (actual)
- Study completion
- 31 Jul 2018 (actual)
- First posted
- 25 Sep 2014 (estimated)
- Results
- Posted 25 Aug 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Acute Myeloid Leukemia (AML) is currently treated with chemotherapy by combining several drugs with different ways of inhibiting the cell growth. In this trial, standard chemotherapeutics that have proven their effectiveness for years, Ara-C and Idarubicin, will be combined with a new drug called Selinexor.
Selinexor inhibits the growth of cancer cells by keeping certain proteins in the nucleus which control the cell growth.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- In the initial protocol, 25 patients are included in the clinical trial on the schedule described as cohort 1. After an amendment 15 further patients are included on the schedule described as cohort 2.
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 / Selinexor 40 mg/m^2 in combination with cytarabine and idarubicin | Experimental | Drug: Selinexor, Drug: Idarubicin, Drug: CytarabineAll enrolled patients are treated with cytarabine at a dose of 100 mg/m² continuous infusion (day 1-7) and idarubicin at a dose of 10 mg/m^2 iv (day 1,3,5) every 4 weeks and selinexor for up to 2 induction cycles. If a second cycle is applied idarubicin is only given on day 1 and 3. Selinexor is administered at a dose of 40 mg/m^2 twice weekly orally starting on day 2 (total of 8 doses per induction cycle). |
| Cohort 2 / Selinexor 60 mg flat dose in combination with cytarabine and idarubicin | Experimental | Drug: Selinexor, Drug: Idarubicin, Drug: CytarabineAll enrolled patients are treated with cytarabine at a dose of 100 mg/m^2 continuous infusion (day 1-7) and idarubicin at a dose of 10 mg/m^2 iv (day 1,3,5) every 4 weeks and selinexor for up to 2 induction cycles. If a second cycle is applied idarubicin is only given on day 1 and 3. Selinexor is administered at a flat dose of 60 mg twice weekly orally in weeks 1-3 of a 4-week cycle starting on day 2 (total of 6 doses per induction cycle). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Cytological or histological diagnosis of AML with the exception of promyelocytic leukemia (AML M3)
- Patients must have relapsed/refractory disease (relapse after stem cell transplantation is permitted) as defined as:
- Men and women aged ≥18 years and eligible for standard dose of chemotherapy (7+3);
- A period of at least 3 weeks needs to have elapsed since last treatment (with the exception of hydroxyurea) before participating in this study. Hydroxyurea induction therapy to reduce peripheral blast counts is permitted prior to initiation of treatment on protocol. Treatment may begin in <3 weeks from last treatment if deemed in the best interest of the patient after discussion with the PI of the study;
- ECOG performance status ≤ 2
Key exclusion criteria (13 listed)
- Treatment with any investigational agent within four weeks.
- Cumulative anthracycline dose (daunorubicin or equivalent) >360 mg/m^2
- HIV infection
- Presence of any medical or psychiatric condition which may limit full compliance with the study, including but not limited to:
- Presence of CNS leukemia
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-330Patients receive Selinexor as specified in arm/group description (8 doses of 40 mg/m^2 or 6 doses of 60 mg per induction cycle). | Drug | Cohort 1 / Selinexor 40 mg/m^2 in combination with cytarabine and idarubicin, Cohort 2 / Selinexor 60 mg flat dose in combination with cytarabine and idarubicin |
| IdarubicinInfusion, iv, 10 mg/m^2, on days 1,3,5 in cycle 1, on days 1,3 in cycle 2 | Drug | Cohort 1 / Selinexor 40 mg/m^2 in combination with cytarabine and idarubicin, Cohort 2 / Selinexor 60 mg flat dose in combination with cytarabine and idarubicin |
| CytarabineAlso: Ara-CContinuous infusion day 1 to 7, 100 mg/m^2, iv, | Drug | Cohort 1 / Selinexor 40 mg/m^2 in combination with cytarabine and idarubicin, Cohort 2 / Selinexor 60 mg flat dose in combination with cytarabine and idarubicin |
Primary outcome
Number of Participants With CR/CRi = Overall Reponse Rate
Time frame: 1-2 induction cycles (4 - 8 weeks)
Efficacy of selinexor in combination with standard chemotherapy in patients with relapsed/refractory AML by determination of rate of complete response (CR) or morphologic complete response with incomplete blood count recovery (CRi), as defined by the recommendations on diagnosis and management of AML in adults from an international expert panel, on behalf of the European LeukemiaNet: CR: Absolute Neutrophil count (ANC) >1.0x10^9/L, Platelet count >100x10^9/L, Bone marrow blasts <5%, no Auer rods, no evidence of extramedullary disease. CRi: Same as CR, but ANC may be <1.0x10^9/L and/or Platelet count <100x10^9/L. Patients with morphologic leukemia free-state (MLFS) were included in the group of responders. MLFS: Bone marrow blasts <5%, no Auer rods, no evidence of extramedullary disease. The best response after Selinexor treatment was analyzed, thus the best response after the induction cycle(s).
7 secondary outcomes
Number of Participants With Partial Remission (PR) = Rate of PR
Time frame: 1-2 induction cycles (4 - 8 weeks)
Percentage of Patients Transplanted After Induction Therapy (Stem Cell Transplantation)
Time frame: 1-2 induction cycles (4 - 8 weeks)
Early Death Rate
Time frame: 1 induction cycle (4 weeks)
Overall Survival
Time frame: Time from registration to event, max 2 years
Relapse-Free Survival
Time frame: Time from registration to event, max 2 years
Event-Free Survival
Time frame: Time from registration to event, max 2 years
Progression-Free Survival
Time frame: Time from registration to event, max 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Aug 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
The record lists no contact. Use the official record to reach the sponsor.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Selinexor, Idarubicin and Cytarabine in people with Acute Myeloid Leukemia (Relapsed/Refractory), run by GSO Global Clinical Research BV at 3 sites in Germany.
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 14 inclusion and 13 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 25 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Germany. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Aug 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants With CR/CRi = Overall Reponse Rate (time frame: 1-2 induction cycles (4 - 8 weeks)). 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 25 Aug 2021.