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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03110562




Registration number
NCT03110562
Ethics application status
Date submitted
7/04/2017
Date registered
12/04/2017
Date last updated
26/01/2023

Titles & IDs
Public title
Bortezomib, Selinexor, and Dexamethasone in Patients With Multiple Myeloma
Scientific 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)
Secondary ID [1] 0 0
KCP-330-023
Universal Trial Number (UTN)
Trial acronym
BOSTON
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Myeloma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Selinexor
Treatment: Drugs - Bortezomib
Treatment: Drugs - Dexamethasone

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.

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.


Treatment: Drugs: Selinexor
oral 100 mg dose

Treatment: Drugs: Bortezomib
subcutaneous dose of 1.3 mg/m2

Treatment: Drugs: Dexamethasone
oral dose of 20mg
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free Survival (PFS) as Assessed by IRC
Timepoint [1] 0 0
From date of randomization until IRC-confirmed documented PD or death, censored date, whichever occurred first (up to 32 months)
Secondary outcome [1] 0 0
Overall Response Rate (ORR) as Assessed by IRC
Timepoint [1] 0 0
From date of randomization until disease progression or death, whichever occurred first (maximum duration up to 75 months)
Secondary outcome [2] 0 0
Percentage of Participants With Response Rates
Timepoint [2] 0 0
From date of randomization until disease progression or death, whichever occurred first (maximum duration up to 75 months)
Secondary outcome [3] 0 0
Overall Survival (OS)
Timepoint [3] 0 0
From date of randomization to the date of death or censored date, whichever occurred first (maximum duration of 75 months)
Secondary outcome [4] 0 0
Duration of Response (DOR) as Assessed by IRC
Timepoint [4] 0 0
From the first documentation of response to the first documentation of PD or death or censored date, whichever occurred first (maximum duration up to 75 months)
Secondary outcome [5] 0 0
Time-to-next-treatment (TTNT)
Timepoint [5] 0 0
From date of randomization to start of next anti-MM treatment or death, whichever occurs first (maximum duration of 75 months)
Secondary outcome [6] 0 0
Time-to-response (TTR) as Assessed by IRC
Timepoint [6] 0 0
From date of randomization until the date of first IRC confirmed response (maximum duration up to 75 months)
Secondary outcome [7] 0 0
Number of Participants With Grade >= 2 Peripheral Neuropathy Events
Timepoint [7] 0 0
From date of randomization up to 30 days after last dose of treatment (maximum duration of 75 months)
Secondary outcome [8] 0 0
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
Timepoint [8] 0 0
From date of randomization up to 30 days after last dose of treatment (maximum duration up to 75 months)
Secondary outcome [9] 0 0
Patient-reported Peripheral Neuropathy Measured by European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-CIPN20 Instrument
Timepoint [9] 0 0
Up to 75 months

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

- 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

- Urinary M-protein excretion at least 200 mg/24 hours; or

- 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
24/05/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/09/2023
Actual
Sample size
Target
Accrual to date
Final
402
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [2] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [3] 0 0
Mater Misericordiae Limited and Mater Medical Research - South Brisbane
Recruitment hospital [4] 0 0
Gold Coast University Hospital - Southport
Recruitment hospital [5] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [6] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [7] 0 0
St. Vincent's Hospital Melbourne - Fitzroy
Recruitment hospital [8] 0 0
The Alfred Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
2298 - Waratah
Recruitment postcode(s) [2] 0 0
4029 - Herston
Recruitment postcode(s) [3] 0 0
4101 - South Brisbane
Recruitment postcode(s) [4] 0 0
4215 - Southport
Recruitment postcode(s) [5] 0 0
5000 - Adelaide
Recruitment postcode(s) [6] 0 0
5042 - Bedford Park
Recruitment postcode(s) [7] 0 0
3065 - Fitzroy
Recruitment postcode(s) [8] 0 0
3004 - Melbourne
Recruitment outside Australia
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Florida
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Wolverhampton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Karyopharm Therapeutics Inc
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03110562
Trial related presentations / publications
Public notes

Contacts
Principal investigator
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Email 0 0
Contact person for public queries
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Contact person for scientific queries