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Selinexor and Backbone Treatments of Multiple Myeloma Patients (STOMP)

This study is currently recruiting participants.
Verified November 2017 by Karyopharm Therapeutics Inc
Sponsor:
ClinicalTrials.gov Identifier:
NCT02343042
First Posted: January 21, 2015
Last Update Posted: December 4, 2017
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.
Information provided by (Responsible Party):
Karyopharm Therapeutics Inc
  Purpose
This study will independently assess the efficacy and safety of four combination therapies for the treatment of patients with relapsed/refractory multiple myeloma (RR MM): selinexor + pomalidomide + dexamethasone (SPd), selinexor + bortezomib + dexamethasone (SVd), selinexor + lenalidomide+ dexamethasone (SRd), and selinexor + daratumumab + dexamethasone (SDd). The abbreviations for combination treatments have been revised to use V (Velcade) for bortezomib and R (Revlimid) for lenalidomide.

Condition Intervention Phase
Multiple Myeloma Drug: Selinexor Drug: Dexamethasone Drug: Lenalidomide Drug: Pomalidomide Drug: Bortezomib Drug: Daratumumab Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b/2 Study of Selinexor (KPT-330) in Combination With Backbone Treatments for Relapsed/Refractory Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Karyopharm Therapeutics Inc:

Primary Outcome Measures:
  • Maximal Tolerated Dose (MTD) and Recommended Phase 2 dose (RP2D) for Selinexor [ Time Frame: 12 months ]
    - Determine the MTD and RP2D; selinexor once weekly or twice weekly for all arms.


Secondary Outcome Measures:
  • Number of patients with Adverse Events as a measure of safety and tolerability [ Time Frame: 12 months ]
    - Evaluate the safety and tolerability of SPd (selinexor + pomalidomide + dexamethasone), SVd (selinexor + bortezomib + dexamethasone ), SRd (selinexor + lenalidomide + dexamethasone ), and SDd (selinexor + daratumumab + dexamethasone) in patients with relapsed/refractory multiple myeloma using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), v 4.03.


Estimated Enrollment: 262
Actual Study Start Date: October 2015
Estimated Study Completion Date: April 2018
Estimated Primary Completion Date: March 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 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.

Drug: Selinexor
Tablets
Other Name: KPT-330
Drug: Dexamethasone
Oral tablets in a multi-dose vial.
Other Name: Decadron
Drug: Pomalidomide
4 mg oral tablets
Other Name: Pomalyst
Experimental: Arm 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.

Drug: Selinexor
Tablets
Other Name: KPT-330
Drug: Dexamethasone
Oral tablets in a multi-dose vial.
Other Name: Decadron
Drug: Bortezomib
3.5mg for injection supplied as lyophilized powder in single-use viles for subcutaneous injection.
Other Name: Velcade
Experimental: Arm 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.
Drug: Selinexor
Tablets
Other Name: KPT-330
Drug: Dexamethasone
Oral tablets in a multi-dose vial.
Other Name: Decadron
Drug: Lenalidomide
25mg Oral capsule
Other Name: REVLIMID
Experimental: Arm 4 Selinexor, Low-dose dexamethasone, & Daratumumab (SDd)

Daratumumab at 16mg/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. A cycle is 28 days.

Cohort 4.1: Selinexor 100mg with dexamethasone 40mg once weekly. Cohort 4.2: Selinexor 60mg with dexamethasone 20mg twice weekly;

dexamethasone 40mg weekly, or equivalent dose of other corticosteroid, may be given intravenously or by mouth will also be given (without selinexor: For once weekly dosing, Cycles 1 and 2: Days 2, 3, 9, 10, 16, 17, 23, and 24; Cycles 3-6: Days 2, 3, 16, and 17; Cycles >6: Days 2 and 3. For twice weekly dosing, Cycles 1 and 2: Days 2, 9, 16, 17, 22, 23, and 24; Cycles 3-6: Days 2, 16, 22, 24; Cycles >6: Days 2, 22, and 24.

Drug: Selinexor
Tablets
Other Name: KPT-330
Drug: Dexamethasone
Oral tablets in a multi-dose vial.
Other Name: Decadron
Drug: Daratumumab
16mg/kg Intravenous
Other Name: Darzalex

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), and selinexor + daratumumab + dexamethasone (SDd) in patients with relapsed/refractory multiple myeloma (RR MM).
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Inclusion Criteria:

  1. Histologically confirmed diagnosis, measurable disease and evidence of disease progression of MM, as described below.
  2. Symptomatic MM, based on IMWG guidelines. Patients must have measurable disease as defined by at least one of the following:

    • Serum M-protein ≥ 0.5 g/dL by serum electrophoresis (SPEP) or, for IgA myeloma, by quantitative IgA
    • Urinary M-protein excretion at least 200 mg/24 hours
    • Serum FLC ≥ 100 mg/L, provided that FLC ratio is abnormal
    • If serum protein electrophoresis is felt to be unreliable for routine M-protein measurement, then quantitative Ig levels by nephelometry or turbidometry are acceptable.
  3. Any non-hematological toxicities (except for peripheral neuropathy as described in exclusion criterion #22) that patients experienced from treatments in previous clinical studies must have resolved to ≤ Grade 2 by Cycle 1 Day 1.
  4. Adequate hepatic function within 21 days prior to C1 D1:
  5. Adequate renal function within 21 days prior to C1 D1:
  6. Adequate hematopoietic function within 21 days prior to C1 D1:
  7. SPd (Arm 1) Only:

    Relapsed and refractory MM with:

    • Documented evidence of PD after achieving at least SD for ≥ 1 cycle during a previous MM regimen (i.e., relapsed MM)
    • ≤ 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)
    • Previously undergone ≥ 2 cycles of lenalidomide and a proteasome inhibitor (in separate therapeutic regimens [not for maintenance] or in combination)
  8. SVd (Arm 2) Only:

    Relapsed or refractory MM with:

    • Documented evidence of relapse after ≥ 1 previous line of therapy
    • Not refractory to bortezomib in their most recent line of therapy
  9. SRd (Arm 3) Only:

    • Patients who received ≥ 1 prior therapeutic regimen (prior lenalidomide is allowed as long as patient was not refractory to prior lenalidomide)
  10. SDd (Arm 4 Only):

    • Patients who received ≥ 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent.

Exclusion Criteria:

  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 MM involving the central nervous system (CNS)
  5. Active plasma cell leukemia
  6. Blood (or blood product) transfusions and blood growth factors within 7 days of C1 D1 only for patients enrolling into the Expansion Phase
  7. Radiation, chemotherapy, or immunotherapy or any other anticancer therapy ≤ 2 weeks prior to C1 D1, and radio-immunotherapy within 6 weeks prior to C1 D1. Patients on long-term glucocorticoids during Screening, including use for spinal cord compression, do not require a washout period. Prior radiation is permitted for treatment of fractures or to prevent fractures as well as for pain management
  8. Treatment with an investigational anti-cancer therapy within 3 weeks prior to C1 D1
  9. Prior autologous stem cell transplantation < 1 month, or allogeneic stem cell transplantation < 3 months prior to C1 D1
  10. Active graft versus host disease after allogeneic stem cell transplantation
  11. A life expectancy of < 3 months
  12. Major surgery within 4 weeks prior to C1 D1
  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 C1 D1
    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. Prior history of malignancies: cancer treated with curative intent > 5 years before study enrollment and without evidence of recurrence will be allowed. Cancer treated with curative intent < 5 years previously will not be allowed unless approved by the medical monitor. Exceptions include:

    1. Resected basal or squamous cell carcinoma of the skin
    2. Carcinoma in situ of the cervix
  19. Any active gastrointestinal dysfunction that prevents the patient from swallowing tablets, or interferes with absorption of study treatment
  20. Currently pregnant or breastfeeding
  21. A serious psychiatric or medical condition which, in the opinion of the investigator, could interfere with treatment
  22. Hypersensitivity to any of the treatments for the Arm in which the patient is enrolled
  23. 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 C1 D1)

  24. Prior participation in a selinexor clinical trial
  Contacts and Locations
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): NCT02343042


Contacts
Contact: Michael Kauffman, MD, PhD mkauffman@karyopharm.com
Contact: Sharon Shacham, PhD SShacham@karyopharm.com

Locations
United States, California
Jonnsson Comprehensive Cancer Center / University of Los Angeles Recruiting
Los Angeles, California, United States, 0095
Contact: Gary Schiller, MD, PhD    888-798-0719    GSchiller@mednet.ucla.edu   
Principal Investigator: Gary Schiller, MD, PhD         
United States, New York
Columbia University Recruiting
New York, New York, United States, 10032
Contact: Suzanne Lentzsch, MD    212-305-5065    CTOInformation@columbia.edu   
Principal Investigator: Suzanne Lentzsch, MD         
Wilmot Cancer Center/ University of Rochester Recruiting
Rochester, New York, United States
Contact: Brea Lipe, MD       Brea_Lipe@URMC.Rochester.edu   
Principal Investigator: Brea Lipe, MD         
United States, North Carolina
Duke Institute of Cancer/ Duke University Recruiting
Durham, North Carolina, United States, 27710
Contact: Cristina Gasparetto, MD    919-668-1017    gaspa001@mc.duke.edu   
Principal Investigator: Cristina Gasparetto, MD         
United States, Washington
Swedish Cancer Institute Recruiting
Seattle, Washington, United States, 98109
Contact: William Bensinger, MD    855-922-6237      
Principal Investigator: William Bensinger, MD         
Canada, Alberta
Tom Baker Cancer Center/Alberta Health Services Recruiting
Calgary, Alberta, Canada, T2N 4Z6
Contact: Nizar Bahlis, MD    +1 (403) 944-1880    nbahlis@ucalgary.ca   
Principal Investigator: Nizar Bahlis, MD         
Cross Cancer Institute / University of Alberta Recruiting
Edmonton, Alberta, Canada, T6G 1Z2
Contact: Chris Venner    780-432-8771      
Principal Investigator: Chris Venner, MD         
Canada, British Columbia
Vancouver General Hospital Recruiting
Vancouver,, British Columbia, Canada, V5Z 1M9
Contact: Heather Sutherland    604.736.2033      
Principal Investigator: Heather Sutherland, MD         
Canada, Manitoba
Cancer Care Manitoba Active, not recruiting
Winnipeg, Manitoba, Canada, R3E 0V9
Canada, Newfoundland and Labrador
Memorial Hospital of Newfoundland Recruiting
St. John's, Newfoundland and Labrador, Canada, A1B 3V6
Contact: Debra Bergstrom         
Canada, Nova Scotia
Queen Elizabeth II Health Sciences Center Recruiting
Halifax, Nova Scotia, Canada, B3H 2Y9
Contact: Darrell White         
Principal Investigator: Darrell White, MD         
Canada, Ontario
Princess Margaret Cancer Centre Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Saima Dean    416 946 4501 ext 5241      
Principal Investigator: Christine Chen         
Canada, Quebec
Maisonneuve-Rosemont Hospital Active, not recruiting
Montreal, Quebec, Canada, H1T 2M4
Royal Victoria Hospital / McGill University Active, not recruiting
Montreal, Quebec, Canada, H3A 1A1
Sponsors and Collaborators
Karyopharm Therapeutics Inc
Investigators
Study Director: Michael Kauffman, MD, Ph.D Karyopharm Therapeutics Inc
  More Information

Responsible Party: Karyopharm Therapeutics Inc
ClinicalTrials.gov Identifier: NCT02343042     History of Changes
Other Study ID Numbers: KCP-330-017
First Submitted: January 13, 2015
First Posted: January 21, 2015
Last Update Posted: December 4, 2017
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

Keywords provided by Karyopharm Therapeutics Inc:
Selinexor
KCP-330
STOMP
Multiple Myeloma
Relapsed/Refractory
Dexamethasone
Pomalidomide
Bortezomib
Karyopharm
Lenalidomide
Daratumumab

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Lenalidomide
Pomalidomide
Daratumumab
Thalidomide
Bortezomib
BB 1101
Antibodies, Monoclonal
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids