A Phase II Study of Selinexor Plus Cytarabine and Idarubicin in Patients With Relapsed/Refractory Acute Myeloid Leukemia (AML)

August 1, 2021 updated by: GSO Global Clinical Research BV

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
42

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Hamburg, Germany, 20246
        • Universitätsklinikum Hamburg-Eppendorf
    • Hessen
      • Frankfurt am Main, Hessen, Germany, 60590
        • Universitätsklinikum Frankfurt
    • Niedersachsen
      • Hannover, Niedersachsen, Germany, 30625
        • Medizinische Hochschule Hannover

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Cytological or histological diagnosis of AML with the exception of promyelocytic leukemia (AML M3)

  2. Patients must have relapsed/refractory disease (relapse after stem cell transplantation is permitted) as defined as:

    1. patients with <PR after first cycle of induction chemotherapy, or
    2. patients with <CR(i) after second cycle of induction chemotherapy, or
    3. patients who relapse after conventional chemotherapy or
    4. patients who have undergone a single stem cell transplantation and who have relapse of their AML.
  3. Men and women aged ≥18 years and eligible for standard dose of chemotherapy (7+3);
  4. 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;
  5. ECOG performance status ≤ 2
  6. 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.
  7. Ability to swallow and retain oral medication;
  8. Ability to understand and provide signed informed consent;
  9. Cardiac ejection fraction must be >/=50% (by echocardiography).
  10. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.

Exclusion Criteria:

  1. Treatment with any investigational agent within four weeks.
  2. Cumulative anthracycline dose (daunorubicin or equivalent) >360 mg/m^2
  3. HIV infection
  4. Presence of any medical or psychiatric condition which may limit full compliance with the study, including but not limited to:
  5. Presence of CNS leukemia
  6. Unresolved toxicity from previous anti-cancer therapy or incomplete recovery from surgery.

  7. For patients after SCT as part of prior treatment:

    1. Necessity of immunosuppressive drugs
    2. GvHD > grade 1
  8. 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.
  9. Ongoing cardiac dysrhythmias of NCI CTCAE >/= Grade 2.
  10. 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.
  11. Clinically significant bleeding within 1 month

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Cohort 1 / Selinexor 40 mg/m^2 in combination with cytarabine and idarubicin

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).
Drug: Selinexor
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).
Other Names:
  • KPT-330
Drug: Idarubicin
Infusion, iv, 10 mg/m^2, on days 1,3,5 in cycle 1, on days 1,3 in cycle 2
Drug: Cytarabine
Continuous infusion day 1 to 7, 100 mg/m^2, iv,
Other Names:
  • Ara-C
Experimental: Cohort 2 / Selinexor 60 mg flat dose in combination with cytarabine and idarubicin

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).
Drug: Selinexor
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).
Other Names:
  • KPT-330
Drug: Idarubicin
Infusion, iv, 10 mg/m^2, on days 1,3,5 in cycle 1, on days 1,3 in cycle 2
Drug: Cytarabine
Continuous infusion day 1 to 7, 100 mg/m^2, iv,
Other Names:
  • Ara-C

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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).
1-2 induction cycles (4 - 8 weeks)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of Participants With Partial Remission (PR) = Rate of PR
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 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).
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)
Percentage of patients being transplanted after induction therapy (stem cell transplantation)
1-2 induction cycles (4 - 8 weeks)
Early Death Rate
Time Frame: 1 induction cycle (4 weeks)
Early death was defined as death before the end of the first induction cycle.
1 induction cycle (4 weeks)
Overall Survival
Time Frame: Time from registration to event, max 2 years
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.
Time from registration to event, max 2 years
Relapse-Free Survival
Time Frame: Time from registration to event, max 2 years
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.
Time from registration to event, max 2 years
Event-Free Survival
Time Frame: Time from registration to event, max 2 years
Event-free survival (EFS) was calculated from the time of informed consent until death, not achieving CR/CRi or relapse after CR/CRi.
Time from registration to event, max 2 years
Progression-Free Survival
Time Frame: Time from registration to event, max 2 years

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%.
Time from registration to event, max 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
GSO Global Clinical Research BV

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Karyopharm Therapeutics Inc

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 31, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 31, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 16, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 23, 2014

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 25, 2014

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 25, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 1, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • SAIL
  • 2014-000526-37 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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