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Study of Selinexor (KPT- 330), Lenalidomide, & Dexamethasone in Relapsed/Refractory Multiple Myeloma Patients (SLAM)

Primary Purpose

Multiple Myeloma

Status
Withdrawn
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Selinexor
Lenalidomide
Dexamethasone
Sponsored by
Karyopharm Therapeutics Inc
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma focused on measuring KPT-330, Selinexor, Multiple Myeloma, Relapsed/refractory, Lenalidomide, Dexamethasone, Karyopharm

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Histologically confirmed diagnosis, measurable disease and evidence of disease progression of MM.
  • Relapsed or refractory to the most recently received therapy. Relapsed is defined as documented evidence of PD after achieving at least SD for ≥ 1 cycle. Refractory disease is defined as ≤ 25% response (i.e., patients never achieved minimal response or better) or progression during therapy or within 60 days after completion of therapy.
  • Symptomatic MM, based on IMWG guidelines. Patients must have measurable disease.

Exclusion Criteria:

  • Smoldering MM.
  • Multiple myeloma that does not express M-protein or FLC (i.e., non-secretory MM is excluded), and quantitative immunoglobulin levels cannot be used instead.
  • Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome
  • Active MM involving the central nervous system (CNS).

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Experimental

    Arm Label

    A: Selinexor (1x/week), Lenalidomide, & Dexamethasone

    B: Selinexor (2x/week), Lenalidomide, & Dexamethasone

    Arm Description

    Lenalidomide will be dosed initially at 15 mg daily, and if that dose is tolerated per dose-limiting toxicity (DLT criteria,) it will be increased to 25 mg for that arm. Selinexor will be started at 80 mg (~45 mg/m2) once weekly in combination with dexamethasone 40 mg once weekly with each dose of selinexor. If the selinexor 80 mg dose is tolerated per DLT criteria, the dose will be increased to 100 mg (~60 mg/m2) and evaluated for MTD, tolerability and efficacy.

    Lenalidomide will be dosed initially at 15 mg daily, and if that dose is tolerated per DLT criteria, it will be increased to 25 mg for that arm. Selinexor will be started at 60 mg (~35 mg/m2) twice weekly in combination with dexamethasone 20 mg twice weekly with each dose of selinexor; dexamethasone 20 mg will also be given, without selinexor, on Days 22 and 24. If the selinexor 60 mg dose is tolerated per DLT criteria, the dose will be increased to 80 mg (~45 mg/m2) and evaluated for MTD, tolerability and efficacy.

    Outcomes

    Primary Outcome Measures

    Determine maximum tolerated dose (MTD)
    Determine the maximum tolerated dose (MTD) of selinexor in the combination SLd in patients with RR MM, as determined by dose limiting toxicities (DLTs), efficacy, and safety
    Overall response rate (ORR)
    According to the International Myeloma Working Group [IMWG] criteria, Overall Response Rate (ORR) includes: stringent complete response [sCR], complete response [CR], very good partial response [VGPR], and partial response [PR]

    Secondary Outcome Measures

    Full Information

    First Posted
    March 10, 2015
    Last Updated
    January 24, 2023
    Sponsor
    Karyopharm Therapeutics Inc
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    1. Study Identification

    Unique Protocol Identification Number
    NCT02389543
    Brief Title
    Study of Selinexor (KPT- 330), Lenalidomide, & Dexamethasone in Relapsed/Refractory Multiple Myeloma Patients
    Acronym
    SLAM
    Official Title
    A Multi-Center, Phase 1/2, Open-Label Study of Selinexor (KPT- 330), Lenalidomide, and Dexamethasone in Patients With Relapsed/Refractory Multiple Myeloma
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    January 2023
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    Terminated this trial and added a Lenalidomide arm to KCP-330-017
    Study Start Date
    July 2015 (undefined)
    Primary Completion Date
    January 2018 (Anticipated)
    Study Completion Date
    February 2018 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Karyopharm Therapeutics Inc

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    This is an open-label, randomized clinical study with two stages to assess the maximum tolerated dose (MTD), efficacy, and safety of selinexor, lenalidomide, and dexamethasone (SLd) in patients with relapsed/refractory (RR) multiple myeloma (MM). The stages are dose escalation (Phase 1) and expansion (Phase 2).
    Detailed Description
    In Phase 1 (Dose Escalation), patients will be randomized to either once-weekly (Arm A) or twice- weekly (Arm B) dosing with selinexor. Dose escalation will be performed within each arm for both lenalidomide and selinexor to determine the selinexor MTD for that arm. Each arm will be expanded until approximately 17 patients have been treated at the MTD in each arm. The Sponsor and Investigator will review the MTD, efficacy, and safety data from Phase 1 to determine which dose schedule (Arm A or B) to be used as the RP2D dose in the Expansion Phase. In Phase 2 (Expansion), patients who had received the MTD dose that was nominated for RP2D will continue at the same dose. Patients who did not receive the RP2D for that arm will stay on their Phase 1 dose. Additional patients will be accrued, as needed, to achieve the target population size of approximately 34 patients at the RP2D.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Multiple Myeloma
    Keywords
    KPT-330, Selinexor, Multiple Myeloma, Relapsed/refractory, Lenalidomide, Dexamethasone, Karyopharm

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1, Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    A: Selinexor (1x/week), Lenalidomide, & Dexamethasone
    Arm Type
    Experimental
    Arm Description
    Lenalidomide will be dosed initially at 15 mg daily, and if that dose is tolerated per dose-limiting toxicity (DLT criteria,) it will be increased to 25 mg for that arm. Selinexor will be started at 80 mg (~45 mg/m2) once weekly in combination with dexamethasone 40 mg once weekly with each dose of selinexor. If the selinexor 80 mg dose is tolerated per DLT criteria, the dose will be increased to 100 mg (~60 mg/m2) and evaluated for MTD, tolerability and efficacy.
    Arm Title
    B: Selinexor (2x/week), Lenalidomide, & Dexamethasone
    Arm Type
    Experimental
    Arm Description
    Lenalidomide will be dosed initially at 15 mg daily, and if that dose is tolerated per DLT criteria, it will be increased to 25 mg for that arm. Selinexor will be started at 60 mg (~35 mg/m2) twice weekly in combination with dexamethasone 20 mg twice weekly with each dose of selinexor; dexamethasone 20 mg will also be given, without selinexor, on Days 22 and 24. If the selinexor 60 mg dose is tolerated per DLT criteria, the dose will be increased to 80 mg (~45 mg/m2) and evaluated for MTD, tolerability and efficacy.
    Intervention Type
    Drug
    Intervention Name(s)
    Selinexor
    Other Intervention Name(s)
    KPT-330
    Intervention Description
    Two different dosing schedules will be tested, once weekly and twice weekly. If the selinexor 80 mg dose is tolerated, the dose will be increased to 100 mg.
    Intervention Type
    Drug
    Intervention Name(s)
    Lenalidomide
    Intervention Description
    In both arms, lenalidomide will be started at 15 mg/day (Dose Level 1) and, if tolerated per DLT criteria, will be escalated to 25 mg/day (Dose Level 2).
    Intervention Type
    Drug
    Intervention Name(s)
    Dexamethasone
    Intervention Description
    Dexamethasone will be given in combination with each dose of selinexor on the once weekly treatment arm. For the twice weekly arm dexamethasone will be given in combination with each dose of selinexor and will also be given without selinexor on Days 22 and 24.
    Primary Outcome Measure Information:
    Title
    Determine maximum tolerated dose (MTD)
    Description
    Determine the maximum tolerated dose (MTD) of selinexor in the combination SLd in patients with RR MM, as determined by dose limiting toxicities (DLTs), efficacy, and safety
    Time Frame
    12 months
    Title
    Overall response rate (ORR)
    Description
    According to the International Myeloma Working Group [IMWG] criteria, Overall Response Rate (ORR) includes: stringent complete response [sCR], complete response [CR], very good partial response [VGPR], and partial response [PR]
    Time Frame
    12 months

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Histologically confirmed diagnosis, measurable disease and evidence of disease progression of MM. Relapsed or refractory to the most recently received therapy. Relapsed is defined as documented evidence of PD after achieving at least SD for ≥ 1 cycle. Refractory disease is defined as ≤ 25% response (i.e., patients never achieved minimal response or better) or progression during therapy or within 60 days after completion of therapy. Symptomatic MM, based on IMWG guidelines. Patients must have measurable disease. Exclusion Criteria: Smoldering MM. Multiple myeloma that does not express M-protein or FLC (i.e., non-secretory MM is excluded), and quantitative immunoglobulin levels cannot be used instead. Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome Active MM involving the central nervous system (CNS).

    12. IPD Sharing Statement

    Learn more about this trial

    Study of Selinexor (KPT- 330), Lenalidomide, & Dexamethasone in Relapsed/Refractory Multiple Myeloma Patients

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