Bortezomib, Selinexor, and Dexamethasone in Patients With Multiple Myeloma



Status:Recruiting
Conditions:Blood Cancer, Hematology, Hematology
Therapuetic Areas:Hematology, Oncology
Healthy:No
Age Range:18 - Any
Updated:11/4/2018
Start Date:May 24, 2017
End Date:June 2020
Contact:Michael Kauffman, MD, PhD
Email:MKauffman@Karyopharm.com
Phone:(617) 658-0600

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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)

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.


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.
We found this trial at
22
sites
520 Techwood Drive
Danville, Kentucky 40422
Principal Investigator: Emmanuel Nidhiry, MD
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201 Dowman Dr
Atlanta, Georgia 30303
(404) 727-6123
Principal Investigator: Ajay Nooka, MD, MPH, FACP
Emory University Emory University, recognized internationally for its outstanding liberal artscolleges, graduate and professional schools,...
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Ames, Iowa 50010
Principal Investigator: Debra Prow, MD
McFarland Clinic, PC It has been over 65 years since the founders of McFarland Clinic...
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Ames, IA
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2000 East Greenville Street
Anderson, South Carolina 29621
Principal Investigator: John Doster, MD
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Anderson, SC
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Baltimore, Maryland 20742
(301) 405-1000
Principal Investigator: Ashraf Badros, M.D., M.B., Ch.B.
University of Maryland As a globally-connected university offering a world-class education, the University of Maryland...
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Bolivar, Missouri 65613
Principal Investigator: Leonid Shunyakov, MD
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Bolivar, MO
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Cincinnati, Ohio 45267
Principal Investigator: Tahir Latif, MBBS MBA FACP
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Cincinnati, OH
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Dallas, Texas 75246
Principal Investigator: Moshe Levy, MD
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Dallas, Texas 75390
Principal Investigator: Larry Anderson, MD, PhD
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Dallas, TX
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Darlinghurst, New South Wales 2010
Principal Investigator: Nada Hamad, MBBS FRACP FRCPA
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Darlinghurst,
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2620 West Faidley Avenue
Grand Island, Nebraska 68803
Principal Investigator: Mehmet Copur, M.D. F.A.C.P.
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Honolulu, Hawaii 96819
Principal Investigator: Jennnifer Carney, MD
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104 Northwest 31st Street
Lawton, Oklahoma 73505
Principal Investigator: Jose Najera, MD
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Louisville, Kentucky 40207
Principal Investigator: Don Stevens, MD
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New York, New York
Principal Investigator: Sundar Jagannath, MD
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Paramus, New Jersey 07652
Principal Investigator: Jason Suh, MD
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600 South Dixie Highway
Plantation, Florida 33324
Principal Investigator: Jason Tache, DO
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2850 Northwest Nicolai Street
Portland, Oregon 97210
Principal Investigator: Abdul Hai Mansoor, MD
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100 Port Washington Boulevard
Roslyn, New York 11576
Principal Investigator: Dilip Patel, MD
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1414 Southwest 8th Avenue
Topeka, Kansas 66606
Principal Investigator: Muhammad Salamat, MD, MBBS
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401 9th Avenue Northwest
Watertown, South Dakota 57201
Principal Investigator: Bipinkumar Amin, MD, MBBS
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3333 Silas Creek Parkway
Winston-Salem, North Carolina 27103
Principal Investigator: Franklin Chen, MD
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