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

This study is currently recruiting participants.
Verified June 2017 by Karyopharm Therapeutics Inc
Sponsor:
ClinicalTrials.gov Identifier:
NCT03110562
First Posted: April 12, 2017
Last Update Posted: June 12, 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 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® or generic equivalent) 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. After progressive disease (PD), patients in the Vd Arm may cross over to SVd treatment. Patients who cross over will be referred to as SVdX patients.

Condition Intervention Phase
Multiple Myeloma Drug: Selinexor Drug: Bortezomib Drug: Dexamethasone Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Karyopharm Therapeutics Inc:

Primary Outcome Measures:
  • 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


Estimated Enrollment: 364
Actual Study Start Date: June 7, 2017
Estimated Study Completion Date: June 2020
Estimated Primary Completion Date: June 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: Selinexor
oral 100 mg dose
Drug: Bortezomib
subcutaneous dose of 1.3 mg/m2
Other Name: Velcade® or generic equivalent
Drug: Dexamethasone
oral dose of 20mg
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.
Drug: Bortezomib
subcutaneous dose of 1.3 mg/m2
Other Name: Velcade® or generic equivalent
Drug: Dexamethasone
oral dose of 20mg

  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 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. Resolution of any clinically significant non-hematological toxicities (if any) from previous treatments to ≤ Grade 1 by C1D1.
  6. Adequate hepatic function within 28 days prior to C1D1
  7. Adequate renal function within 28 days prior to C1D1
  8. Adequate hematopoietic function within 7 days prior to C1D1

Exclusion Criteria:

  1. Has received selinexor or another XPO1 inhibitor previously.
  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. Intolerance, hypersensitivity, or contraindication to glucocorticoids.
  12. Radiation, chemotherapy, or immunotherapy or any other anticancer therapy ≤ 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. 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.
  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): NCT03110562


Contacts
Contact: Sharon Shacham, PhD (617)658-0600 SShacham@Karyopharm.com
Contact: Michael Kauffman, MD, PhD (617)658-0600 MKauffman@Karyopharm.com

Locations
Canada, Alberta
Southern Alberta Cancer Research Institute / University of Calgary Not yet recruiting
Calgary, Alberta, Canada, T2N 4Z6
Contact: Nizar Bahlis, MD       nbahlis@ucalgary.ca   
Principal Investigator: Nizar Bahlis, MD         
Cross Cancer Institute / University of Alberta Not yet recruiting
Edmonton, Alberta, Canada, T6G 1Z2
Contact: Chris Venner, MD       ChristopherPaul.Venner@albertahealthservices.ca   
Principal Investigator: Chris Venner, MD         
Canada, British Columbia
Vancouver General Hospital Not yet recruiting
Vancouver, British Columbia, Canada, V5Z 1M9
Contact: Heather Sutherland, MD, PhD, FRCPC       hsutherl@bccancer.bc.ca   
Principal Investigator: Heather Sutherland, MD, PhD, FRCPC         
Canada, Nova Scotia
Queen Elizabeth II Health Sciences Center Recruiting
Halifax, Nova Scotia, Canada, B3H 2Y9
Contact: Darrell White, MD, MSc, FRCPC, FACP       Darrell.White@nshealth.ca   
Principal Investigator: Darrell White, MD, MSc, FRCPC, FACP         
Canada, Ontario
Princess Margaret Cancer Research Recruiting
Toronto, Ontario, Canada, M5G 1X5
Contact: Donna Reece, MD       Donna.Reece@uhn.edu   
Principal Investigator: Donna Reece, MD         
Canada, Quebec
Maisonneuve-Rosemont Hospital Not yet recruiting
Montreal, Quebec, Canada, H1T 2M4
Contact: Richard LeBlanc, M.D., FRCPC       rleblanc.hmr@ssss.gouv.qc.ca   
Principal Investigator: Richard LeBlanc, M.D., FRCPC         
Royal Victoria Hospital / McGill University Not yet recruiting
Montreal, Quebec, Canada, H3A 1A1
Contact: Michael Sebag       michael.sebag@mcgill.ca   
Principal Investigator: Michael Sebag, MD         
L'Hôtel-Dieu de Québec Recruiting
Quebec City, Quebec, Canada, G1R 2J6
Contact: Marc Lalancette, MD       marclalancette@hotmail.com   
Principal Investigator: Marc Lalancette, MD         
Canada, Saskatchewan
Saskatoon Cancer Center Recruiting
Saskatoon, Saskatchewan, Canada, S7N 4H4
Contact: Waleed Sabry, MD       Waleed.Sabry@saskcancer.ca   
Principal Investigator: Waleed Sabry, MD         
Greece
Alexandra General Hospital, Therapeutic Clinic Recruiting
Athens, Greece, 11528
Contact: Meletios-Athanasios Dimopoulos, MD    (+) 30 697 731 19 99    mdimop@med.uoa.gr   
Principal Investigator: Meletios-Athanasios Dimopoulos, MD         
Sponsors and Collaborators
Karyopharm Therapeutics Inc
  More Information

Responsible Party: Karyopharm Therapeutics Inc
ClinicalTrials.gov Identifier: NCT03110562     History of Changes
Other Study ID Numbers: KCP-330-023
First Submitted: April 7, 2017
First Posted: April 12, 2017
Last Update Posted: June 12, 2017
Last Verified: June 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Karyopharm Therapeutics Inc:
Relapsed or Refractory Multiple Myeloma
RRMM
Bortezomib
Dexamethasone

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
Bortezomib
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors