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Trial record 6 of 6 for:    LIPE

Selinexor and Backbone Treatments of Multiple Myeloma Patients (STOMP)

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ClinicalTrials.gov Identifier: NCT02343042
Recruitment Status : Recruiting
First Posted : January 21, 2015
Last Update Posted : September 24, 2019
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 September 24, 2019
Actual Study Start Date  ICMJE October 2015
Estimated Primary Completion Date May 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 9, 2019)
  • Phase 1 (Dose-escalation) [ Time Frame: 12 months ]
    Determine the maximum tolerated dose (MTD) for once weekly (QW) and twice weekly (BIW) selinexor dose Cohorts in the 7 Arms being evaluated.
  • Phase 1 (Dose-escalation) [ Time Frame: 12 months ]
    Determine the recommended Phase-2 dose (RP2D) for each Arm.
  • Phase 2 (Expansion) [ Time Frame: 12 months ]
    Determine the overall response rate (ORR; primary endpoint) 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 ]
    Determine the ORR for each Arm in patients with free light chain (FLC) MM.
  • Phase 2 (Expansion) [ Time Frame: 12 months ]
    Determine the duration of response (DOR) for each Arm.
  • Phase 2 (Expansion) [ Time Frame: 12 months ]
    Determine the 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 Complete list of historical versions of study NCT02343042 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 9, 2019)
  • Phase 1 (Dose-escalation) [ Time Frame: 12 months ]
    Evaluate safety and tolerability (per Arm) using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
  • Phase 2 (Expansion) [ Time Frame: 12 months ]
    • Assess time to progression (TTP), progression-free survival (PFS), and overall survival (OS) for each Arm.
  • Phase 2 (Expansion) [ Time Frame: 12 months ]
    Assess safety, tolerability, and incidence of adverse events (AEs) per CTCAE version 4.03 for each Arm.
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
Brief Summary

This study will independently assess the efficacy and safety of six combination therapies for the treatment of patients with Relapsed/Refractory Multiple Myeloma (RR MM) and Newly Diagnosed Multiple Myeloma (NDMM). The combinations to be evaluated include: selinexor + pomalidomide + dexamethasone (SPd), selinexor + bortezomib + dexamethasone (SVd), selinexor + lenalidomide + dexamethasone (SRd), selinexor + pomalidomide + dexamethasone + bortezomib (SPVd), selinexor + daratumumab + dexamethasone (SDd), and selinexor + carfilzomib + dexamethasone (SKd).

The abbreviations for combination treatments have been revised to use V (Velcade) for bortezomib, R (Revlimid) for lenalidomide, D (Darzalex) for daratumumab, and K (Kyprolis) for carfilzomib.

Detailed Description

Multi-center, open-label, randomized (for dose schedule) clinical study with dose escalation (Phase 1) and expansion (Phase 2) stages to independently assess the maximum tolerated dose (MTD,) efficacy, and safety of selinexor + pomalidomide + dexamethasone (SPd), selinexor + bortezomib + dexamethasone (SVd), selinexor + lenalidomide + dexamethasone (SRd), selinexor + pomalidomide + dexamethasone + bortezomib (SPVd), selinexor + daratumumab + dexamethasone (SDd), and selinexor + carfilzomib + dexamethasone (SKd) in patients with relapsed/refractory multiple myeloma (RR MM) and newly diagnosed multiple myeloma (ND MM).

SPVd arm will not open for enrollment until further notice.

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 Name: KPT-330
  • Drug: Dexamethasone
    Oral tablets in a multi-dose vial.
    Other Name: Decadron
  • Drug: Lenalidomide
    25 mg Oral capsule
    Other Name: REVLIMID
  • Drug: Pomalidomide
    4 mg oral tablets
    Other Name: Pomalyst
  • Drug: Bortezomib
    3.5 mg for injection supplied as lyophilized powder in single-use viles for subcutaneous injection.
    Other Name: Velcade
  • Drug: Daratumumab
    16 mg/kg Intravenous
    Other Name: Darzalex
  • Drug: Carfilzomib
    56 mg/m2 Intravenous
    Other Name: Kyprolis
Study Arms  ICMJE
  • Experimental: 1: Selinexor, Low-dose Dexamethasone & Pomalidomide (SPd)

    Pomalidomide will be dosed at 4 mg daily for 21 days per cycle.

    Cohort 1.1: Selinexor 80 mg with dexamethasone 40 mg once weekly.

    Cohort 1.2: Selinexor 60 mg with dexamethasone 20 mg twice weekly; dexamethasone 40 mg weekly will also be given (without selinexor) on Days 22 & 24.

    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: Selinexor 80 mg with dexamethasone 40 mg once weekly. Bortezomib 1.3 mg/m2 subcutaneous (SC) once weekly.

    Cohort 2.2: Selinexor 60 mg with dexamethasone 20 mg twice weekly; dexamethasone 40 mg weekly will also be given on Days 29 and 31. Bortezomib 1.3 mg/m2 SC dosed once weekly.

    Interventions:
    • Drug: Selinexor
    • Drug: Dexamethasone
    • Drug: Bortezomib
  • Experimental: 3: Selinexor, Low-dose dexamethasone, & Lenalidomide (SRd)

    Lenalidomide at 25mg daily for 21 days per 28 day cycle.

    Cohort 3.1: Selinexor 80mg with dexamethasone 40mg once weekly.

    Cohort 3.2: Selinexor 60mg with dexamethasone 20mg twice weekly; dexamethasone 40mg weekly will also be given (without selinexor) on Days 22 and 24.

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

    Cohort 4.1: Selinexor 100 mg with dexamethasone 40 mg once weekly. Pomalidomide at 4 mg daily for 21 days per 28 day cycle. Bortezomib 1.3 mg/m2 subcutaneous (SC) once weekly.

    Cohort 4.2: Selinexor 60 mg with dexamethasone 20 mg twice weekly. Pomalidomide at 4 mg daily for 21 days per 28 day cycle. Bortezomib 1.3 mg/m2 subcutaneous (SC) once weekly.

    Note: This arm is not open for enrollment at any institution in this study.

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

    Daratumumab at 16 mg/kg IV every week for cycles 1 and 2; then every 2 weeks for cycles 3-6, then once a month for cycles 6 and beyond.

    Cohort 5.1: Selinexor 100 mg once weekly, with dexamethasone or equivalent dose of other corticosteroid, given intravenously or by mouth, 40 mg weekly in single or divided doses.

    Cohort 5.2: Selinexor 60 mg twice weekly with dexamethasone or equivalent dose of other corticosteroid, given intravenously or by mouth, 40 mg weekly in single or divided doses.

    Interventions:
    • Drug: Selinexor
    • Drug: Dexamethasone
    • Drug: Daratumumab
  • Experimental: 6: Selinexor, Low-dose Dexamethasone, & Carfilzomib (Skd)
    Cohort 6.1: Selinexor 100 mg with dexamethasone 40 mg once weekly. Carfilzomib 56 mg/m2 IV once weekly per 28 day cycle.
    Interventions:
    • Drug: Selinexor
    • Drug: Dexamethasone
    • Drug: Carfilzomib
  • Experimental: 7: Selinexor,Low-dose Dexamethasone,Lenalidomide (SRd) NDMM
    Cohort 7.1 in Newly Diagnosed MM: Selinexor 60 mg with dexamethasone 40 mg once weekly. Lenalidomide at 25 mg daily for 21 days per 28 day cycle.
    Interventions:
    • Drug: Selinexor
    • Drug: Dexamethasone
    • Drug: Lenalidomide
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 5, 2018)
321
Original Estimated Enrollment  ICMJE
 (submitted: January 15, 2015)
140
Estimated Study Completion Date  ICMJE May 2020
Estimated Primary Completion Date May 2020   (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, measurable disease and evidence of disease progression of MM, as described below.
  4. Symptomatic MM, based on IMWG guidelines. 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 serum protein electrophoresis 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.
  5. Any non-hematological toxicities (except for peripheral neuropathy as described in exclusion criterion #24) that patients experienced from treatments in previous clinical studies must have resolved to ≤ Grade 2 by Cycle 1 Day 1.
  6. Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2.
  7. Adequate hepatic function within 21 days prior to C1 D1:

    • For SPd and SRd: 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 < 2.5x ULN)
    • For SVd, SPVd and SDd): 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
  8. Adequate renal function within 21 days prior to C1 D1:

    • Estimated creatinine clearance of (calculated using the formula of Cockroft and Gault):
    • ≥ 20 mL/min for SVd, SPVd, and SDd Arms
    • ≥ 45 mL/min for SPd Arm (as requested by the manufacturer)
    • > 50 mL/min for SRd Arm
  9. Adequate hematopoietic function within 21 days prior to C1 D1: total white blood cell (WBC) count ≥ 1,500/mm3, ANC ≥ 1000/mm3, hemoglobin (Hb) ≥ 8.0 g/dL, and platelet count ≥ 75,000/mm3. For expansion cohorts only, platelet counts > 50,000/mm3; for patients in whom ≥ 50% of bone marrow nucleated cells are plasma cells, platelets or ≥ 30,000/mm3 are acceptable for expansion cohorts. Patients receiving hematopoietic growth factor support, including erythropoietin (EPO), darbepoetin, granulocyte-colony stimulating factor (G-CSF), granulocyte macrophagecolony stimulating factor (GM-CSF), and platelet stimulators (e.g., eltrombopag or romiplostim) may continue to do so. However, patients in the escalation cohorts must be platelet transfusion independent for > 1 week in order to be enrolled in the study.
  10. Female patients of child-bearing potential must agree to use dual methods 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 child-bearing potential. Acceptable methods of contraception are condoms with contraceptive foam, oral, implantable or injectable contraceptives, contraceptive patch, intrauterine device, diaphragm with spermicidal gel, or a sexual partner who is surgically sterilized or post-menopausal. For both male and female patients, effective methods of contraception must be used throughout the study and for three months following the last dose.

    SPd (Arm 1) Only:

  11. Relapsed and refractory MM with:

    1. Documented evidence of PD after achieving at least 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 proteasome inhibitor (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:

  12. 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:

  13. 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:

  14. Patients whose MM is relapsing after ≥ 1 prior therapy with progression on their last therapy.

    SDd (Arm 5) Only:

  15. 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.
  16. Patients must not have received prior daratumumab therapy (Cohort 5.3 ONLY - dose expansion at RP2D).

    SKd (Arm 6) Only:

  17. Patients may have received prior bortezomib or carfilzomib therapy, however their MM must NOT be refractory to carfilzomib.

    SRd in NDMM (Arm 7) Only:

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

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. Blood (or blood product) transfusions and blood growth factors within 7 days of C1D1 (only for patients enrolling into the Expansion Phase)
  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. In the SVd (Arm 2) only: Prior history of neuropathy Grade > 2, or Grade 2 neuropathy with pain at screening (within 21 days prior to C1D1)
  23. Prior exposure to a SINE compound, including selinexor
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 September 2019

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