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Selinexor and Backbone Treatments of Multiple Myeloma Patients (STOMP)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02343042
Recruitment Status : Recruiting
First Posted : January 21, 2015
Last Update Posted : July 2, 2020
Sponsor:
Information provided by (Responsible Party):
Karyopharm Therapeutics Inc

Tracking Information
First Submitted Date  ICMJE January 13, 2015
First Posted Date  ICMJE January 21, 2015
Last Update Posted Date July 2, 2020
Actual Study Start Date  ICMJE October 2015
Estimated Primary Completion Date May 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 15, 2020)
  • Phase 1 (Dose-escalation) [ Time Frame: 12 months ]
    Maximum tolerated dose (MTD) for once weekly (QW) and twice weekly (BIW) selinexor dose cohorts in the 9 Arms being evaluated
  • Phase 1 (Dose-escalation) [ Time Frame: 12 months ]
    Recommended Phase-2 dose (RP2D) for each Arm
  • Phase 1 (Dose-escalation) [ Time Frame: 14 days ]
    Maximum plasma concentration (Cmax) of selinexor over a dosing interval when given with and without clarithromycin
  • Phase 1 (Dose-escalation) [ Time Frame: 14 days ]
    Total exposure of selinexor in the blood (AUC0-last) from the time of dosing to the last measurable concentration collected when given with and without clarithromycin
  • Phase 2 (Expansion) [ Time Frame: 12 months ]
    Overall response rate (ORR) for each Arm independently. ORR to include stringent complete response (sCR), complete response (CR), very good partial response (VGPR), and partial response (PR), according to the International Myeloma Working Group (IMWG) criteria.
  • Phase 2 (Expansion) [ Time Frame: 12 months ]
    Duration of response (DOR) for each Arm
  • Phase 2 (Expansion) [ Time Frame: 12 months ]
    Clinical benefit rate (CBR), defined as ORR plus minimal response (MR) for each Arm
Original Primary Outcome Measures  ICMJE
 (submitted: January 15, 2015)
Maximal Tolerated Dose (MTD) for Selinexor [ Time Frame: 2 months ]
Determine the maximal tolerated dose (MTD) for selinexor in:
  • Arm 1 (SdP): Selinexor + dexamethasone + pomalidomide
  • Arm 2 (SdB): Selinexor + dexamethasone + bortezomib - Determine the recommended Phase 2 dose (RP2D; selinexor once weekly or twice weekly) for both arms.
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: January 15, 2015)
Number of patients with Adverse Events as a measure of safety and tolerability [ Time Frame: 2 months ]
- Evaluate the safety and tolerability of SdP (Selinexor + dexamethasone + pomalidomide) and SdB (Selinexor + dexamethasone + bortezomib) in patients with resistant/refractory multiple myeloma using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), v 4.03.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Selinexor and Backbone Treatments of Multiple Myeloma Patients
Official Title  ICMJE A Phase 1b/2 Study of Selinexor (KPT-330) in Combination With Backbone Treatments for Relapsed/Refractory Multiple Myeloma and Newly Diagnosed Multiple Myeloma
Brief Summary

This study will independently assess the efficacy and safety of 8 combination therapies in 9 arms, in dose-escalation/-evaluation and expansion phases, for the treatment of patients with relapsed/refractory multiple myeloma (RRMM) and newly diagnosed multiple myeloma (NDMM). The combinations to be evaluated are:

  • Arm 1: Selinexor + dexamethasone + pomalidomide (SPd)
  • Arm 2: Selinexor + dexamethasone + bortezomib (SVd); enrollment complete
  • Arm 3: Selinexor + dexamethasone + lenalidomide (SRd) in RRMM; enrollment complete
  • Arm 4: Selinexor + dexamethasone + pomalidomide + bortezomib (SPVd)
  • Arm 5: Selinexor + dexamethasone + daratumumab (SDd); enrollment complete
  • Arm 6: Selinexor + dexamethasone + carfilzomib (SKd)
  • Arm 7: Selinexor + dexamethasone + lenalidomide (SRd) in NDMM
  • Arm 8: Selinexor + dexamethasone + ixazomib (SNd)
  • Arm 9: Selinexor + dexamethasone + pomalidomide + elotuzumab (SPEd)

Selinexor pharmacokinetics:

  • PK Run-in (Days 1-14):

Starting in protocol version 8.0, patients enrolled to any arm in the Dose Escalation Phase (i.e., Arm 4 SPVd, Arm 6 SKd, Arm 8 SNd, Arm 9 SPEd) will also first be enrolled to a pharmacokinetics (PK) Run-in period until 9 patients have been enrolled to this period to evaluate the PK of selinexor before and after co-administration with a strong CYP3A4 inhibitor.

Detailed Description

This is a multi-center, open-label, clinical study with Dose Escalation (Phase 1) and Expansion (Phase 2) to independently assess the MTD, efficacy , and safety of 8 combination therapies in 9 arms in patients with RRMM and NDMM. Patients will be assigned to treatment arms based on their diagnoses and treatment histories. For 9 patients, a PK Run-in period will precede Cycle 1 (DLT evaluation) to assess selinexor PK when co-administered with a strong CYP3A4 inhibitor. In the Dose Escalation Phase (Phase 1): (a) in Arm 1 (SPd), Arm 2 (SVd), and Arm 3 (SRd in RRMM), patients will be randomized to either QW or BIW selinexor dosing cohorts; (b) in Arm 5 (SDd), patients will be sequentially assigned in blocks of 3 to either QW or BIW selinexor dosing; (c) in Arm 4 (SPVd), Arm 6 (SKd), Arm 7 (Srd in NDMM), Arm 8 (SNd), and Arm 9 (SPEd), patients will be assigned to QW selinexor dosing.

Starting in protocol version 8.0, patients enrolled to the Dose Escalation Phase of Arm 4 (SPVd), Arm 6 (SKd), Arm 8 (SNd), and Arm 9 (SPEd) will first be enrolled to a 14-day PK Run-in period (selinexor +/- clarithromycin) until 9 patients have been enrolled. During this 14-day PK Run-in period, selinexor 40 mg will be administered alone on Day 1, clarithromycin 500 mg twice daily (BID) will be administered on Days 2-8, and selinexor 40 mg will again be administered on Day 8 with the morning clarithromycin dose. Blood samples for PK analysis will be collected pre-dose and 1 (± 10 min), 1.5 (± 10 min), 2 (± 10 min), 3 (± 10 min), 4 (± 10 min), 5 (± 10 min), 6 (± 10 min), 8 (± 10 min), and 24 h (± 30 min) hours after selinexor is dosed on Day 1 (without clarithromycin) and Day 8 (with clarithromycin). Patients will then proceed to the DLT evaluation period that will begin after the completion of the 14-day PK Run-in period; this day will be designated as Cycle 1 Day 1 (C1D1) in the Dose Escalation Phase.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Multiple Myeloma
Intervention  ICMJE
  • Drug: Selinexor
    Tablets
    Other Names:
    • KPT-330
    • XPOVIO®
  • Drug: Dexamethasone
    Oral tablets in a multi-dose vial
    Other Name: Decadron®
  • Drug: Lenalidomide
    Oral capsule
    Other Name: Revlimid®
  • Drug: Pomalidomide
    Oral tablets
    Other Name: Pomalyst®
  • Drug: Bortezomib
    Subcutaneous Injection (single use vial)
    Other Name: Velcade®
  • Drug: Daratumumab
    Intravenous Infusion
    Other Name: Darzalex®
  • Drug: Carfilzomib
    Intravenous Infusion
    Other Name: Kyprolis®
  • Drug: Ixazomib
    Oral capsule
    Other Name: Ninlaro®
  • Drug: Elotuzumab
    Intravenous Infusion
    Other Name: Empliciti®
  • Drug: Clarithromycin
    Tablets
    Other Name: Biaxin
Study Arms  ICMJE
  • Experimental: 1: Selinexor, Low-dose Dexamethasone & Pomalidomide (SPd)

    Each cycle is 28 days

    Cohort 1.1: SEL 60/80/100 mg PO once weekly DEX 40 mg PO once weekly POM 2/3/4 mg PO Days 1-21

    Cohort 1.2: SEL 40/60/80 mg PO twice weekly DEX 20 mg PO twice weekly POM 3/4 mg PO Days 1-21

    Interventions:
    • Drug: Selinexor
    • Drug: Dexamethasone
    • Drug: Pomalidomide
  • Experimental: 2: Selinexor, Low-dose Dexamethasone & Bortezomib (SVd)

    One cycle is either 21 or 35 days (depending on bortezomib dosing schedule)

    Cohort 2.1: SEL 60/80/100 mg PO once weekly DEX 40 mg PO once weekly BOR 1.3 mg/m² subcutaneous (SC) once weekly

    Cohort 2.2: SEL 40/60/80 mg PO twice weekly DEX 20 mg PO twice weekly BOR 1.3 mg/m² subcutaneous (SC) once weekly

    Interventions:
    • Drug: Selinexor
    • Drug: Dexamethasone
    • Drug: Bortezomib
  • Experimental: 3: Selinexor, Low-dose DEX, & Lenalidomide (SRd) in RR MM

    Each cycle is 28 days

    Cohort 3.1: SEL 40/60/80/100 mg PO once weekly DEX 40 mg PO once weekly LEN 15/25 mg PO Days 1-21

    Cohort 3.2: SEL 40/60/80 mg PO twice weekly DEX 20 mg PO twice weekly LEN 15/25 mg PO Days 1-21

    Interventions:
    • Drug: Selinexor
    • Drug: Dexamethasone
    • Drug: Lenalidomide
  • Experimental: 4:Selinexor,Low-dose dexamethasone,Pomalidomide,Velcade (SPVd)

    PK Run-in Period: Selinexor & Clarithromycin:

    • For the first 9 patients enrolled into this dose escalation arm
    • 14 day run-in period after which patients will proceed to Dose-Escalation Phase C1D1

    Selinexor 40 mg will be dosed on Day 1 and 8. Clarithromycin 500 mg will be dosed twice daily on Days 2-8.

    PK samples will be collected on Day 1 and 8 at 1, 1.5, 2, 3, 4, 5, 6, 8, and 24 hours post dose.

    Dose-escalation Phase:

    • All patients enrolled into this Arm
    • Each cycle is 28 days.

    Cohort 4.1:

    SEL 20/40/60 mg PO once weekly DEX 40 mg PO once weekly POM 2/4 mg PO Days 1-21 BOR 1.3 mg/m² subcutaneous (SC) once weekly

    Interventions:
    • Drug: Selinexor
    • Drug: Dexamethasone
    • Drug: Pomalidomide
    • Drug: Bortezomib
    • Drug: Clarithromycin
  • Experimental: 5: Selinexor, Low-dose dexamethasone, & Daratumumab (SDd)

    Each cycle is 28 days

    Cohort 5.1:

    SEL 80/100 mg PO once weekly DEX 40 mg once weekly (IV or PO) DARA: 16 mg/kg IV infusion Cycle 1-2: Once weekly Cycle 3-6: Every other week Cycle 6 and greater: Once a month

    Cohort 5.2:

    SEL: 60 mg PO twice weekly DEX: 40 mg weekly (IV or PO) DARA: 16 mg/kg IV infusion Cycle 1-2: Once. weekly Cycle 3-6: Every other week Cycle 6 and greater: Once a month

    Interventions:
    • Drug: Selinexor
    • Drug: Dexamethasone
    • Drug: Daratumumab
  • Experimental: 6: Selinexor, Low-dose dexamethasone, & Carfilzomib (SKd)

    PK Run-in Period: Selinexor & Clarithromycin:

    • For the first 9 patients enrolled into this dose escalation arm
    • 14 day run-in period after which patient will proceed to Dose-Escalation Phase C1D1

    Selinexor 40 mg will be dosed on Day 1 and 8. Clarithromycin 500 mg will be dosed twice daily on Days 2-8.

    PK samples will be collected on Day 1 and 8 at 1, 1.5, 2, 3, 4, 5, 6, 8, and 24 hours post dose.

    Dose-Escalation Phase:

    • All patients enrolled into this Arm
    • Each cycle is 28 days

    Cohort 6.1:

    SEL 60/80/100 mg PO once weekly on days 1, 8, 15, and 22 DEX 40 mg IV or PO once weekly CAR 56 or 70 mg/m² IV infusion once weekly on days 1, 8, 15, and 22.

    Cohort 6.2:

    SEL 60/80/100 mg PO once weekly on day 1, 8, and 15. DEX 40 mg IV or PO once weekly CAR 56 or 70 mg/m² IV infusion once weekly on day 1, 8, and 15.

    Interventions:
    • Drug: Selinexor
    • Drug: Dexamethasone
    • Drug: Carfilzomib
    • Drug: Clarithromycin
  • Experimental: 7: Selinexor,Low-dose DEX & Lenalidomide (SRd) in NDMM

    Each cycle is 28 days

    Cohort 7.1:

    SEL 40/60/80 mg PO once weekly DEX 40 mg PO once weekly LEN 25 mg PO Days 1-21

    Interventions:
    • Drug: Selinexor
    • Drug: Dexamethasone
    • Drug: Lenalidomide
  • Experimental: 8: Selinexor, Low-dose dexamethasone, & Ixazomib (SNd)

    PK Run-in Period: Selinexor & Clarithromycin:

    • For the first 9 patients enrolled into this dose escalation arm
    • 14 day run-in period after which patient will proceed to Dose-Escalation Phase C1D1

    Selinexor 40 mg will be dosed on Day 1 and 8. Clarithromycin 500 mg will be dosed twice daily on Days 2-8.

    PK samples will be collected on Day 1 and 8 at 1, 1.5, 2, 3, 4, 5, 6, 8, and 24 hours post dose.

    Dose-Escalation Phase:

    • All patients enrolled into this Arm
    • Each cycle is 28 days

    Cohort 8.1:

    SEL 60/80/100 mg PO once weekly DEX 20 mg PO twice weekly IXA 3/4 mg PO Days once weekly

    Interventions:
    • Drug: Selinexor
    • Drug: Dexamethasone
    • Drug: Ixazomib
    • Drug: Clarithromycin
  • Experimental: 9: Selinexor, Low-dose DEX, Pomalidomide & Elotuzumab

    PK Run-in Period: Selinexor & Clarithromycin:

    • For the first 9 patients enrolled into this dose escalation arm
    • 14 day run-in period after which patient will proceed to Dose-Escalation Phase C1D1

    Selinexor 40 mg will be dosed on Day 1 and 8. Clarithromycin 500 mg will be dosed twice daily on Days 2-8.

    PK samples will be collected on Day 1 and 8 at 1, 1.5, 2, 3, 4, 5, 6, 8, and 24 hours post dose.

    Dose-Escalation Phase:

    • All patients enrolled into this Arm
    • Each cycle is 28 days

    Cohort 9.1:

    SEL 40/60/80 mg PO once weekly DEX 28/20 mg PO twice weekly POM 2/4 mg PO Days 1-21 ELO 10 mg/kg IV will be given once weekly on Days 1,8, 15 and 22 of Cycles 1-2. Starting on Cycle 3 and continuing for future cycles, elotuzumab will be dosed at 20 mg/kg on Day 1 of each cycle only.

    Interventions:
    • Drug: Selinexor
    • Drug: Dexamethasone
    • Drug: Pomalidomide
    • Drug: Elotuzumab
    • Drug: Clarithromycin
Publications * Bahlis NJ, Sutherland H, White D, Sebag M, Lentzsch S, Kotb R, Venner CP, Gasparetto C, Del Col A, Neri P, Reece D, Kauffman M, Shacham S, Unger TJ, Jeha J, Saint-Martin JR, Shah J, Chen C. Selinexor plus low-dose bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma. Blood. 2018 Dec 13;132(24):2546-2554. doi: 10.1182/blood-2018-06-858852. Epub 2018 Oct 23.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 15, 2020)
437
Original Estimated Enrollment  ICMJE
 (submitted: January 15, 2015)
140
Estimated Study Completion Date  ICMJE May 2022
Estimated Primary Completion Date May 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Written informed consent in accordance with federal, local, and institutional guidelines.
  2. Age ≥ 18 years at the time of informed consent.
  3. Histologically confirmed diagnosis with measurable disease for relapsed/refractory myeloma.
  4. Symptomatic MM for NDMM needing therapy, based on IMWG guidelines.
  5. Patients must have measurable disease as defined by at least one of the following:

    1. Serum M-protein ≥ 0.5 g/dL by serum protein electrophoresis (SPEP) or, for IgA myeloma, by quantitative IgA
    2. Urinary M-protein excretion at least 200 mg/24 hours
    3. Serum FLC ≥ 100 mg/L, provided that FLC ratio is abnormal
    4. If SPEP is felt to be unreliable for routine M-protein measurement (e.g., for IgA MM), then quantitative Ig levels by nephelometry or turbidometry are acceptable
  6. Any non-hematological toxicities (except for peripheral neuropathy as described in exclusion criterion #22) that patients had from treatments in previous clinical studies must have resolved to ≤ Grade 2 by Cycle 1 Day 1.
  7. Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2.
  8. Adequate hepatic function within 28 days prior to C1D1:

    • For SPd, SRd, and SPEd: Total bilirubin < 2x upper limit of normal (ULN) (except patients with Gilbert's syndrome [hereditary indirect hyperbilirubinemia] who must have a total bilirubin of ≤ 3x ULN) and both aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5x ULN
    • For SVd, SPVd, SDd, and SNd: Total bilirubin of < 1.5x ULN (except patients with Gilbert's syndrome [hereditary indirect hyperbilirubinemia] who must have a total bilirubin of ≤ 3x ULN) and both AST and ALT < 2.0x ULN
    • For SKd: Total bilirubin < 2x ULN (except patients with Gilbert's syndrome [hereditary indirect hyperbilirubinemia] who must have a total bilirubin of ≤ 3x ULN) and both AST and ALT < 3.0x ULN
  9. Adequate renal function within 28 days prior to C1D1. Estimated creatinine clearance (CrCl) calculated using the formula of Cockroft and Gault (1976):

    • ≥ 20 mL/min for SVd, SDd, and SKd arms
    • ≥ 30 mL/min for SNd arm
    • ≥ 45 mL/min for SPd, SPVd, and SPEd arms
    • > 60 mL/min for SRd arm
  10. Adequate hematopoietic function within 28 days prior to C1D1: total white blood cell (WBC) count ≥ 1,500/mm³, ANC ≥ 1,000/mm³, hemoglobin (Hb) ≥ 8.0 g/dL, and platelet count ≥ 150,000/mm³.
  11. Female patients of childbearing potential must have a negative serum pregnancy test at Screening. Female patients of childbearing potential and fertile male patients who are sexually active with a female of childbearing potential must use highly effective methods of contraception throughout the study and for 1 week following the last dose of study treatment.

    SPd (Arm 1) Only:

  12. Relapsed and refractory MM with:

    1. Documented evidence of progressive disease (PD) after achieving at least stable disease (SD) for ≥ 1 cycle during a previous MM regimen (i.e., relapsed MM)
    2. ≤ 25% response (i.e., patients never achieved ≥ MR) or PD during or within 60 days from the end of the most recent MM regimen (i.e., refractory MM)
    3. Previously undergone ≥ 2 cycles of lenalidomide and a PI (in separate therapeutic regimens [not for maintenance] or in combination)
    4. In the expansion arm at RP2D, patients must not be pomalidomide refractory

    SVd (Arm 2) Only:

  13. Relapsed or refractory MM with:

    1. Documented evidence of relapse after ≥ 1 previous line of therapy
    2. Not refractory to bortezomib in their most recent line of therapy

    SRd in RRMM (Arm 3) Only:

  14. Patients who received ≥ 1 prior therapeutic regimen (prior lenalidomide is allowed as long as patient's MM was not refractory to prior lenalidomide; patients whose MM was refractory to lenalidomide maintenance regimens will be allowed in this cohort).

    SPVd (Arm 4) Only:

  15. Patients who received 1- 3 prior lines of therapy, including ≥ 2 cycles of lenalidomide and have demonstrated disease progression on their last therapy (may include prior bortezomib, as long as the patient's MM was not refractory to bortezomib therapy), but patients must be pomalidomide-naïve in the Dose Expansion at RP2D (Cohort 4.3 ONLY).

    SDd (Arm 5) Only:

  16. Patients who received ≥ 3 prior lines of therapy, including a PI and an IMiD, or patients with MM refractory to both a PI and an IMiD.
  17. Patients must not have received prior anti-CD38 monoclonal antibodies (Cohort 5.3 ONLY - Dose Expansion at RP2D).

    SKd (Arm 6) Only:

  18. Patients may have received prior PIs; however, their MM must NOT be refractory to carfilzomib.

    SRd in NDMM (Arm 7) Only:

  19. Patients must have symptomatic myeloma per IMWG guidelines with either CRAB criteria or myeloma-defining events and need systemic therapy. No prior systemic therapy for NDMM is permitted other than pulse dose dexamethasone (maximum dose of 160 mg) or corticosteroid equivalent.

    SNd (Arm 8) Only:

  20. Patients must have MM that relapsed after 1 - 3 prior lines of therapy (may not include those with MM refractory to bortezomib or carfilzomib and patients must be ixazomib-naïve).

    SPEd (Arm 9) Only:

  21. Patients who received ≥ 2 prior therapies, including lenalidomide and a PI (in separate or the same regimens), but patients must be pomalidomide-naïve and elotuzumab-naïve in the Dose Expansion at RP2D (Cohort 9.3 ONLY).

Exclusion Criteria:

Patients meeting any of the following exclusion criteria are not eligible to enroll in this study:

  1. Smoldering MM
  2. MM that does not express M-protein or FLC (i.e., non-secretory MM is excluded), and quantitative immunoglobulin levels cannot be used instead
  3. Documented active systemic amyloid light chain amyloidosis
  4. Active plasma cell leukemia
  5. Red Blood Cell (RBC) and platelet transfusions and blood growth factors within 14 days of C1D1.
  6. Radiation, chemotherapy, or immunotherapy or any other anticancer therapy ≤ 2 weeks prior to C1D1, and radio-immunotherapy within 6 weeks prior to C1D1. Patients on long-term glucocorticoids during Screening do not require a washout period. Prior radiation is permitted for treatment of fractures or to prevent fractures as well as for pain management
  7. Patients with history of SCC with residual paraplegia (Dose Escalation Phase only).
  8. Treatment with an investigational anti-cancer therapy within 3 weeks prior to C1D1
  9. Prior autologous stem cell transplantation < 1 month, or allogeneic stem cell transplantation < 3 months prior to C1D1
  10. Active graft versus host disease after allogeneic stem cell transplantation
  11. Life expectancy < 3 months
  12. Major surgery within 4 weeks prior to C1D1
  13. Active, unstable cardiovascular function:

    1. Symptomatic ischemia, or
    2. Uncontrolled clinically-significant conduction abnormalities (e.g., patients with ventricular tachycardia on antiarrhythmics are excluded; patients with 1st degree atrioventricular (AV) block or asymptomatic left anterior fascicular block/right bundle branch block (LAFB/RBBB) will not be excluded), or
    3. Congestive heart failure (CHF) of New York Heart Association (NYHA) Class ≥ 3, or
    4. Myocardial infarction (MI) within 3 months prior to C1D1
    5. Ejection fraction (EF) < 50% at Screening
  14. Uncontrolled active hypertension
  15. Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose
  16. Known active hepatitis A, B or C
  17. Known HIV infection or HIV seropositivity
  18. Any active gastrointestinal dysfunction that prevents the patient from swallowing tablets or interferes with absorption of study treatment
  19. Currently pregnant or breastfeeding
  20. A serious psychiatric or medical condition which, in the opinion of the Investigator, could interfere with treatment
  21. Hypersensitivity to any of the treatments for the Arm in which the patient is enrolled
  22. Prior exposure to a SINE compound, including selinexor

    In the SVd Arm (Arm 2), SPVd (Arm 4), and SNd Arm (Arm 8) only:

  23. Prior history of neuropathy Grade > 2, or Grade ≥ 2 neuropathy with pain at screening (within 28 days prior to C1D1).

    Patients who are eligible for the selinexor PK Run-in only:

  24. Treatment with moderate or strong inhibitors/inducers of CYP3A within 7 days prior to Day 1 of the PK Run-in period
  25. Not able to receive a strong CYP3A4 inhibitor due to concomitant medications

    SKd Arm only:

  26. HBs Ag + plus HBc Ab + even though no active HBV hepatitis. If HBs Ag - plus HBc Ab +, treating physician needs to contact the medical monitor
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Michael Kauffman, MD, PhD mkauffman@karyopharm.com
Contact: Sharon Shacham, PhD SShacham@karyopharm.com
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02343042
Other Study ID Numbers  ICMJE KCP-330-017
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Responsible Party Karyopharm Therapeutics Inc
Study Sponsor  ICMJE Karyopharm Therapeutics Inc
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Michael Kauffman, MD, Ph.D Karyopharm Therapeutics Inc
PRS Account Karyopharm Therapeutics Inc
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP