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A 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

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ClinicalTrials.gov Identifier: NCT02249091
Recruitment Status : Active, not recruiting
First Posted : September 25, 2014
Last Update Posted : February 14, 2018
Sponsor:
Collaborator:
Karyopharm Therapeutics Inc
Information provided by (Responsible Party):
GSO Global Clinical Research BV

Brief 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.

Selinexor inhibits the growth of cancer cells by keeping certain proteins in the nucleus which control the cell growth.


Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia (Relapsed/Refractory) Drug: Selinexor Drug: Idarubcin Drug: Cytarabine Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : September 2014
Estimated Primary Completion Date : June 2018
Estimated Study Completion Date : June 2018


Arm Intervention/treatment
Experimental: Selinexor in combination with cytarabine and idarubicin

All enrolled patients will be treated with cytarabine at a dose of 100 mg/m² continuous infusion (day 1-7) and idarubicin at a dose of 10 mg/m² iv (day 1,3,5) every 4 weeks and selinexor for up to 2 induction cycles. If a second cycles is applied idarubicin is only given on day 1 and 3.

Selinexor will be administered at a dose of 40 mg/m² twice weekly orally starting on day 2 (total of 8 doses per induction cycle).

Drug: Selinexor
Patients receive Selinexor 40 mg/m2 twice weekly orally
Other Name: KPT-330

Drug: Idarubcin
infusion, iv, 10 mg/m2, 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/m2, iv,




Primary Outcome Measures :
  1. Efficacy of Selinexor in combination with standard chemotherapy in patients with relapsed/ refractory AML by determination of rate of complete remission (CR) or morphologic complete remission with incomplete blood count recovery (CRi) after [ Time Frame: After completion of induction therapy (= up to 8 weeks). ]
    CR and CRi as defined by the revised recommendations of the International Working Group for diagnosis, standardization of response criteria in Acute Myeloid Leukemia for AML


Secondary Outcome Measures :
  1. Efficacy of Selinexor in combination with standard chemotherapy in patients with relapsed/ refractory AML by rate of partial remissions [ Time Frame: After 4 and/or 8 weeks of treatment ]
  2. Efficacy of Selinexor in combination with standard chemotherapy in patients with relapsed/ refractory AML by percentage of patients being transplanted after induction therapy [ Time Frame: After 4 and/or 8 weeks of treatment ]
  3. Efficacy of Selinexor in combination with standard chemotherapy in patients with relapsed/ refractory AML by Overall Survival (including early death rate) [ Time Frame: from registration til date of death, max 2 years ]
  4. Efficacy of Selinexor in combination with standard chemotherapy in patients with relapsed/ refractory AML by Event-free survival [ Time Frame: time from registration to event, max 2 years ]
    Events are defined as Death, not achieving a CR or CRi, Relapse after CR or CRi. Disease status will be assessed every 4 weeks.

  5. To evaluate overall safety of Selinexor [ Time Frame: Registration to 30 days after EOT ]
    To evaluate overall safety of Selinexor by assessing adverse events observed during the treatment within this study.


Other Outcome Measures:
  1. To identify the Pharmacokinetics (Cmax) of Selinexor in patients with relapsed/refractory AML [ Time Frame: week 1 of 1st induction cycle ]
    - Limited pharmacokinetics to measure plasma concentration of Selinexor

  2. Pharmacodynamics: Selinexor-induced changes in mRNA levels of tumor suppressor markers in patients with relapsed/refractory AML [ Time Frame: week 1 of each induction cycle ]
  3. Pharmacodynamics: Selinexor-induced changes in plasma cytokine levels patients with relapsed/refractory AML [ Time Frame: week 1 of each induction cycle ]
  4. Pharmacodynamics: Selinexor-induced changes in gene expression profiling of leukemic blasts isolated from patients with relapsed/refractory AML [ Time Frame: prior and after week -1 Selinexor intake ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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/m²
  3. HIV infection
  4. Presence of any medical or psychiatric condition which may limit full compliance with the study, including but not limited to:

    1. Presence of CNS leukemia
    2. Unresolved toxicity from previous anti-cancer therapy or incomplete recovery from surgery.
  5. For patients after SCT as part of prior treatment:

    1. Necessity of immunosuppressive drugs
    2. GvHD > grade 1
  6. 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.
  7. Ongoing cardiac dysrhythmias of NCI CTCAE >/= Grade 2.
  8. 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.
  9. Clinically significant bleeding within 1 month

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02249091


Locations
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Germany
Universitätsklinikum Frankfurt
Frankfurt am Main, Hessen, Germany, 60590
Medizinische Hochschule Hannover
Hannover, Niedersachsen, Germany, 30625
Universitätsklinikum Hamburg-Eppendorf
Hamburg, Germany, 20246
Sponsors and Collaborators
GSO Global Clinical Research BV
Karyopharm Therapeutics Inc

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Responsible Party: GSO Global Clinical Research BV
ClinicalTrials.gov Identifier: NCT02249091     History of Changes
Other Study ID Numbers: SAIL
2014-000526-37 ( EudraCT Number )
First Posted: September 25, 2014    Key Record Dates
Last Update Posted: February 14, 2018
Last Verified: February 2018

Additional relevant MeSH terms:
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Leukemia, Myeloid, Acute
Leukemia, Myeloid
Leukemia
Neoplasms by Histologic Type
Neoplasms
Cytarabine
Idarubicin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors