Clinical Trials /

Selinexor With Induction, Consolidation, and Maintenance Therapy in Treating Older Patients With Acute Myeloid Leukemia

NCT02835222

Description:

This pilot phase II trial studies how well selinexor works when given together with induction, consolidation, and maintenance therapy in treating older patients with acute myeloid leukemia. Selinexor may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cytarabine and daunorubicin hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Selinexor with induction, consolidation, and maintenance therapy may kill more cancer cells in older patients with acute myeloid leukemia.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Selinexor With Induction, Consolidation, and Maintenance Therapy in Treating Older Patients With Acute Myeloid Leukemia
  • Official Title: A Pilot Phase II Study of Selinexor in Combination With Induction/Consolidation/Maintenance Therapy in Older AML Patients

Clinical Trial IDs

  • ORG STUDY ID: IRB00039092
  • SECONDARY ID: NCI-2016-00951
  • SECONDARY ID: CCCWFU 22316
  • SECONDARY ID: P30CA012197
  • NCT ID: NCT02835222

Conditions

  • Untreated Adult Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
Cytarabine.beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-Beta-D-arabinofuranosylcytosine, 1.beta.-D-Arabinofuranosylcytosine, 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-, 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-, Alexan, Ara-C, ARA-cell, Arabine, Arabinofuranosylcytosine, Arabinosylcytosine, Aracytidine, Aracytin, Aracytine, Beta-Cytosine Arabinoside, CHX-3311, Cytarabinum, Cytarbel, Cytosar, Cytosar-U, Cytosine Arabinoside, Cytosine-.beta.-arabinoside, Cytosine-beta-arabinoside, Erpalfa, Starasid, Tarabine PFS, U 19920, U-19920, Udicil, WR-28453cytarabine, daunorubicin, selinexor
Daunorubicin HydrochlorideCerubidin, Cerubidine, Cloridrato de Daunorubicina, Daunoblastin, Daunoblastina, Daunoblastine, Daunomycin Hydrochloride, Daunomycin, hydrochloride, Daunorubicin.HCl, Daunorubicini Hydrochloridum, FI-6339, Ondena, RP-13057, Rubidomycin Hydrochloride, Rubilemcytarabine, daunorubicin, selinexor
SelinexorCRM1 Nuclear Export Inhibitor KPT-330, KPT-330, Selective Inhibitor of Nuclear Export KPT-330, SINE KPT-330cytarabine, daunorubicin, selinexor

Purpose

This pilot phase II trial studies how well selinexor works when given together with induction, consolidation, and maintenance therapy in treating older patients with acute myeloid leukemia. Selinexor may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cytarabine and daunorubicin hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Selinexor with induction, consolidation, and maintenance therapy may kill more cancer cells in older patients with acute myeloid leukemia.

Detailed Description

      PRIMARY OBJECTIVES:

      I. Assess the feasibility of adding selinexor to induction, consolidation and maintenance
      therapy of elderly acute myeloid leukemia (AML) patients.

      SECONDARY OBJECTIVES:

      I. To assess the safety of administering selinexor under the proposed study regimen.

      II. To assess response and survival endpoints of patients receiving the proposed study
      regimen.

      III. To assess the rate of allogeneic stem cell transplantation.

      OUTLINE:

      INDUCTION THERAPY: Patients receive cytarabine intravenously (IV) on days 1-7, daunorubicin
      hydrochloride IV on days 1-3, and selinexor orally (PO) twice weekly from day 1. Treatment
      continues for 14 days in the absence of disease progression or unacceptable toxicity.

      RE-INDUCTION THERAPY: Patients whose disease has not responded receive cytarabine IV on days
      1-5, daunorubicin hydrochloride IV on days 1-2, and selinexor PO twice weekly. Treatment
      continues for 14 days in the absence of disease progression or unacceptable toxicity.

      CONSOLIDATION THERAPY: Patients in remission receive cytarabine IV every 12 hours on days 1,
      3 and 6, and selinexor PO twice weekly from day 1. Treatment repeats every 42 days for up to
      3 courses in the absence of disease progression or unacceptable toxicity.

      MAINTENANCE THERAPY: Patients who have had a response and have not gone on to transplant
      receive selinexor PO twice weekly. Treatment continues for 4 weeks in the absence of disease
      progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up for 14 days and then every 3
      months for up to 1 year.
    

Trial Arms

NameTypeDescriptionInterventions
cytarabine, daunorubicin, selinexorExperimentalINDUCTION: Cytarabine IV on days 1-7, daunorubicin hydrochloride IV on days 1-3, and selinexor PO twice weekly from day 1. Treatment continues for 14 days in the absence of disease progression or unacceptable toxicity. RE-INDUCTION: Disease has not responded receive cytarabine IV on days 1-5, daunorubicin hydrochloride IV on days 1-2, and selinexor PO twice weekly. Treatment continues for 14 days in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: In remission receive cytarabine IV every 12 hours for a total 6 doses days 1-3, and selinexor PO twice weekly from day 1. Treatment repeats every 42 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Have had a response, completed all planned consolidation, have not gone to transplant receive selinexor on Days 1 and 8 for cycle 1 only, then Day 1 for cycles 2-4; Day 1 of every 4th cycle. Treatment continues until progression or unacceptable toxicity.
  • Cytarabine
  • Daunorubicin Hydrochloride
  • Selinexor

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have histologically or cytologically documented newly diagnosed de novo
             Acute Myeloid Leukemia (non-APL) that has not yet been treated. Hydrea and ATRA
             previous treatments are acceptable.

          -  Patients must not have a secondary AML (defined as a history of prior radiation
             therapy or systemic chemotherapy, CMML or MDS not treated with a hypomethylating
             agent) however history of previous MDS treated with a hypomethylating agent IS
             allowed.

          -  Hydroxyurea may be used to control leukocytosis, provided that it is without Grade >2
             toxicity, and can be taken until start of therapy.

          -  Age >60 years.

          -  ECOG performance status of ≤ 2 and fit for induction therapy in the opinion of the
             treating physician.

          -  Laboratory values ≤2 weeks must be:

          -  AST(SGOT)/ALT(SGPT)≤ 2.5 X institutional upper limit of normal

          -  Bilirubin ≤ 2 X ULN (3X if known history of Gilbert'syndrome)

          -  Creatinine clearance (CrCl) must be > 20 mL/min

          -  Baseline left ventricular ejection fraction of at least 40% by MUGA or ECHO.

          -  Female patients of childbearing potential must agree to use 2 methods of contraception
             (including 1 highly effective and 1 effective method of contraception) and have a
             negative serum pregnancy test at Screening. Male patients must use an effective
             barrier method of contraception if sexually active with a female of childbearing
             potential. For both male and female patients, effective methods of contraception must
             be used throughout the study and for 3 months following the last dose of study
             treatment. Please refer to Section 6.4.4 of this protocol.

          -  Ability to understand and the willingness to sign an IRB-approved informed consent
             document.

        Exclusion Criteria:

          -  Patients who have received any therapy other than hydroxyurea or ATRA with the purpose
             of treating their AML or patients with Acute Promyelocytic Leukemia are not eligible.

          -  Patients with a secondary AML (defined as a history of prior radiation therapy or
             systemic chemotherapy, antecedent MDS, MPN or CMML) CMML or MDS not treated with a
             hypomethylating agent) however history of previous MDS treated with a hypomethylating
             agent IS allowed.

          -  Patients having received prior radiotherapy, treatment with cytotoxic agents,
             treatment with biologic agents or any anti-cancer therapy for a non-AML malignancy
             within the 4 weeks prior to treatment with selinexor, or those who have not fully
             recovered from the acute, non-hematological, non-infectious toxicities of any prior
             treatment with cytotoxic drugs, radiotherapy or other anti-cancer modalities (returned
             to baseline status as noted before most recent treatment).

          -  Patients with another active malignancy that requires treatment excluding non-melanoma
             skin cancers.

          -  Patients that have received a chemotherapy regimen with stem cell support in the
             previous 6 months.

          -  Patients with known central nervous system involvement should be excluded from this
             clinical trial because the penetration of selinexor into the CNS is not currently
             known.

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to selinexor.

          -  Uncontrolled concurrent illness including, but not limited to symptomatic congestive
             heart failure, unstable angina pectoris, or cardiac arrhythmia

          -  Psychiatric illness/social situations that would limit compliance with study
             requirements.

          -  Patients with known HIV infection or hepatitis (Note: Patients with known HIV
             infection are excluded because patients with an immune deficiency are at increased
             risk of lethal infections when treated with marrow-suppressive therapy.

          -  Pregnant women are excluded from this study because of the potential for teratogenic
             or abortifacient effects. Because there is an unknown but potential risk for adverse
             events in nursing infants secondary to treatment of the mother, breastfeeding should
             be discontinued.

          -  Patients unable to swallow tablets, patients with malabsorption syndrome, or any other
             GI disease or GI dysfunction that could interfere with absorption of study treatment

          -  Prior exposure to a SINE compound
      
Maximum Eligible Age:N/A
Minimum Eligible Age:60 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Feasibility of combining selinexor with induction/consolidation/maintenance therapy assessed by percentage of patients eligible for maintenance therapy who complete at least 3 courses
Time Frame:Up to 1 year
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Incidence of adverse events assessed by Common Terminology Criteria for Adverse Events version 4.0
Time Frame:Up to 1 year
Safety Issue:
Description:The frequency of toxicities experienced by the participants will be presented by type and grade in an effort to monitor and report safety of the treatment.
Measure:Overall survival
Time Frame:Up to 1 year
Safety Issue:
Description:Kaplan-Meier estimation will be used to analyze the overall survival.
Measure:Progress-free survival
Time Frame:Up to 1 year
Safety Issue:
Description:
Measure:Rate of allogeneic stem cell transplantation
Time Frame:Up to 1 year
Safety Issue:
Description:
Measure:Rate of complete remission
Time Frame:Up to 1 year
Safety Issue:
Description:Confidence intervals will be calculated around the estimates of the response rate (complete remission and complete remission with incomplete recovery).

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Wake Forest University Health Sciences

Last Updated

November 12, 2019