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Bortezomib, Selinexor, and Dexamethasone in Patients With Multiple Myeloma (BOSTON)

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ClinicalTrials.gov Identifier: NCT03110562
Recruitment Status : Active, not recruiting
First Posted : April 12, 2017
Last Update Posted : November 27, 2019
Sponsor:
Information provided by (Responsible Party):
Karyopharm Therapeutics Inc

Tracking Information
First Submitted Date  ICMJE April 7, 2017
First Posted Date  ICMJE April 12, 2017
Last Update Posted Date November 27, 2019
Actual Study Start Date  ICMJE May 24, 2017
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 17, 2018)
Compare progression-free survival (PFS) based on the Independent Review Committee's (IRC's) disease outcome assessments in patients randomized to the SVd Arm versus the Vd Arm [ Time Frame: 15 months ]
PFS, defined as time from date of randomization until the first date of PD, per International Myeloma Working Group (IMWG) response criteria, or death due to any cause, whichever occurs first. For the purposes of PFS determination, PD will be determined by the IRC.
Original Primary Outcome Measures  ICMJE
 (submitted: April 7, 2017)
  • Compare progression-free survival (PFS) based on the Independent Review Committee's (IRC's) disease outcome assessments in patients randomized to the SVd Arm versus the Vd Arm [ Time Frame: 15 months ]
    PFS, defined as time from date of randomization until the first date of PD, per International Myeloma Working Group (IMWG) response criteria, or death due to any cause, whichever occurs first. For the purposes of PFS determination, PD will be determined by the IRC.
  • Compare the overall response rate (ORR) based on the IRC's response outcome assessments in patients randomized to the SVd Arm versus the Vd Arm [ Time Frame: 15 months ]
    ORR, defined as any response ≥ PR based on the IRC's response outcome assessments, according to the IMWG response criteria
Change History Complete list of historical versions of study NCT03110562 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Bortezomib, Selinexor, and Dexamethasone in Patients With Multiple Myeloma
Official Title  ICMJE A Phase 3 Randomized, Controlled, Open-label Study of Selinexor, Bortezomib, and Dexamethasone (SVd) Versus Bortezomib and Dexamethasone (Vd) in Patients With Relapsed or Refractory Multiple Myeloma (RRMM)
Brief Summary This Phase 3, 2-arm, randomized, active comparator-controlled, open-label, multicenter study will compare the efficacy and health-related quality of life (HR-QoL) and assess the safety of selinexor plus bortezomib (Velcade®) plus low-dose dexamethasone (SVd) versus bortezomib plus low-dose dexamethasone (Vd) in adult patients with RRMM who have received 1 to 3 prior anti-multiple myeloma (MM) regimens. Crossover from the Vd Arm to a treatment that includes selinexor (i.e., SVdX or SdX) will be allowed at the point of IRC-confirmed objective disease progression per the IMWG criteria for patients in the Vd Arm.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Multiple Myeloma
Intervention  ICMJE
  • Drug: Selinexor
    oral 100 mg dose
  • Drug: Bortezomib
    subcutaneous dose of 1.3 mg/m2
    Other Name: Velcade®
  • Drug: Dexamethasone
    oral dose of 20mg
Study Arms  ICMJE
  • Active Comparator: selinexor+bortezomib+dexamethasone (SVd)
    Selinexor will be given on Days 1, 8, 15, 22, and 29 of each 35-day cycle. Bortezomib will be given Days 1, 8, 15, and 22 of each 35-day cycle. Dexamethasone will be given Days 1, 2, 8, 9, 15, 16, 22, 23, 29, and 30 of each 35-day cycle.
    Interventions:
    • Drug: Selinexor
    • Drug: Bortezomib
    • Drug: Dexamethasone
  • Active Comparator: bortezomib+dexamethasone (Vd)
    Bortezomib will be given Days 1, 4, 8, and 11 of each 21-day cycle for the first 8 cycles. For Cycles ≥ 9, bortezomib will be given on Days 1, 8, 15, and 22 of each 35-day cycle. Dexamethasone will be given on Days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle for the first 8 cycles. For Cycles ≥ 9, dexamethasone will be given on Days 1, 2, 8, 9, 15, 16, 22, 23, 29, and 30 of each 35-day cycle.
    Interventions:
    • Drug: Bortezomib
    • Drug: Dexamethasone
Publications * Not Provided

*   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 Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: May 29, 2019)
402
Original Estimated Enrollment  ICMJE
 (submitted: April 7, 2017)
364
Estimated Study Completion Date  ICMJE June 2020
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Histologically confirmed MM with measurable disease per IMWG guidelines as defined by at least 1 of the following:

    1. Serum M-protein ≥ 0.5 g/dL (> 5 g/L) by serum protein electrophoresis (SPEP) or for immunoglobulin (Ig) A myeloma, by quantitative serum IgA levels; or
    2. Urinary M-protein excretion at least 200 mg/24 hours; or
    3. Serum free light chain (FLC) ≥ 100 mg/L, provided that the serum FLC ratio is abnormal.
  2. Had at least 1 prior anti-MM regimen and no more than 3 prior anti-MM regimens. Induction therapy followed by stem cell transplant and consolidation/maintenance therapy will be considered as 1 anti-MM regimen.
  3. Documented evidence of progressive MM (based on the Investigator's determination according to the modified IMWG response criteria) on or after their most recent regimen.
  4. Prior treatment with bortezomib or other Proteasome Inhibitor (PI) is allowed, provided all of the following criteria are met:

    • Best response achieved with prior bortezomib at any time was ≥ PR and with the last PI (PI therapy (alone or in combination) was ≥ PR, AND
    • Participant did not discontinue bortezomib due to ≥ Grade 3 related toxicity, AND
    • Must have had at least a 6-month PI-treatment-free interval prior to Cycle 1 Day 1 (C1D1) of study treatment.
  5. Must have an ECOG Status score of 0, 1, or 2.
  6. Written informed consent in accordance with federal, local, and institutional guidelines.
  7. Age ≥18 years.
  8. Resolution of any clinically significant non-hematological toxicities (if any) from previous treatments to ≤ Grade 1 by C1D1.
  9. Adequate hepatic function within 28 days prior to C1D1.
  10. Adequate renal function within 28 days prior to C1D1.
  11. Adequate hematopoietic function within 7 days prior to C1D1.
  12. 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 3 months following the last dose of study treatment.

Exclusion Criteria:

  1. Prior exposure to a SINE compound (i.e. an XPO-1 inhibitor), including selinexor.
  2. Prior malignancy that required treatment, or has shown evidence of recurrence (except for non-melanoma skin cancer or adequately treated cervical carcinoma in situ) during the 5 years prior to randomization.
  3. Any concurrent medical condition or disease (e.g., uncontrolled active hypertension, uncontrolled active diabetes, active systemic infection, etc.) that is likely to interfere with study procedures.
  4. Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within 1 week prior to C1D1.
  5. Active plasma cell leukemia.
  6. Documented systemic light chain amyloidosis.
  7. MM involving the central nervous system.
  8. Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome.
  9. Spinal cord compression.
  10. Greater than Grade 2 neuropathy or ≥ Grade 2 neuropathy with pain at baseline, regardless of whether or not the patient is currently receiving medication
  11. Known intolerance, hypersensitivity, or contraindication to glucocorticoids.
  12. Radiation, chemotherapy, or immunotherapy or any other anticancer therapy (including investigational therapies) ≤ 2 weeks prior to C1D1. Localized radiation to a single site at least 1 week before C1D1 is permitted. Glucocorticoids within 2 weeks of C1D1 are permitted. Patients on long-term glucocorticoids during Screening do not require a washout period but must be able to tolerate the specified dexamethasone dose in this study.
  13. Prior autologous stem cell transplantation < 1 month or allogeneic stem cell transplantation < 4 months prior to C1D1.
  14. Active graft versus host disease (after allogeneic stem cell transplantation) at C1D1.
  15. Pregnant or breastfeeding females.
  16. Body Surface Area < 1.4 m² at baseline, calculated by the Dubois or Mosteller method.
  17. Life expectancy of < 4 months.
  18. Major surgery within 4 weeks prior to C1D1.
  19. Active, unstable cardiovascular function:

    1. Symptomatic ischemia, or
    2. Uncontrolled clinically significant conduction abnormalities (e.g., patients with ventricular tachycardia on anti-arrhythmics are excluded; patients with first-degree atrioventricular block or asymptomatic left anterior fascicular block/right bundle branch block will not be excluded), or
    3. Congestive heart failure of New York Heart Association Class ≥ 3 or known left ventricular ejection fraction < 40%, or
    4. Myocardial infarction within 3 months prior to C1D1.
  20. Known active human immunodeficiency virus (HIV) infection or HIV seropositivity
  21. Known active hepatitis A, B, or C infection; or known to be positive for hepatitis C virus ribonucleic acid (RNA) or hepatitis B virus surface antigen.
  22. Any active gastrointestinal dysfunction interfering with the patient's ability to swallow tablets, or any active gastrointestinal dysfunction that could interfere with absorption of study treatment.
  23. Any active, serious psychiatric, medical, or other conditions/situations that, in the opinion of the Investigator, could interfere with treatment, compliance, or the ability to give informed consent.
  24. Contraindication to any of the required concomitant drugs or supportive treatments.
  25. Patients unwilling or unable to comply with the protocol, including providing 24-hour urine samples for urine protein electrophoresis at the required time points.
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 information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Austria,   Belgium,   Bulgaria,   Canada,   Czechia,   France,   Germany,   Greece,   Hungary,   India,   Israel,   Italy,   Poland,   Romania,   Russian Federation,   Serbia,   Spain,   Ukraine,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03110562
Other Study ID Numbers  ICMJE KCP-330-023
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Karyopharm Therapeutics Inc
Study Sponsor  ICMJE Karyopharm Therapeutics Inc
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Michael Kauffman, MD, PhD Karyopharm Therapeutics Inc
PRS Account Karyopharm Therapeutics Inc
Verification Date November 2019

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