Bortezomib, Selinexor, and Dexamethasone in Patients With Multiple Myeloma

Phase 3

Completed

• Conditions: Multiple Myeloma
• Interventions: Drug: Selinexor; Drug: Bortezomib; Drug: Dexamethasone

• Registration Number: NCT03110562
• Lead Sponsor: Karyopharm Therapeutics Inc

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 available

Study Timeline

• Study First Submitted: 2017-04-07
• Study First Submitted QC: 2017-04-07
• Study First Posted: 2017-04-12
• Study Start: 2017-05-24
• Primary Completion: 2020-02-18
• Results First Submitted: 2021-06-15
• Results First Submitted QC: 2021-06-15
• Results First Posted: 2021-07-08
• Study Completion: 2022-05-12
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-25
• Last Update Posted: 2024-08-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 402

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 (normal FLC ratio: 0.26 to 1.65).

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:

   1. 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
   2. Participant did not discontinue bortezomib due to ≥ Grade 3 related toxicity, AND
   3. 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. Patients with chronic, stable Grade 2 non-hematological toxicities may be included following approval from the Medical Monitor.

9. Adequate hepatic function within 28 days prior to C1D1.

   1. Total bilirubin <1.5 × upper limit of normal (ULN) (except patients with Gilbert's syndrome who must have a total bilirubin of <3 × ULN), and
   2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) normal to <2 × ULN.

10. Adequate renal function within 28 days prior to C1D1 (estimated creatinine clearance [CrCl] of ≥20 mL/min, calculated using the formula of Cockroft and Gault):

(140-Age) × Mass (kg)/(72 × creatinine mg/dL) Multiply by 0.85 if the patient is female, or if CrCl is ≥20 mL/min as measured by 24-hour urine collection.

11. Adequate hematopoietic function within 7 days prior to C1D1: total white blood cell (WBC) count ≥1500/mm3, absolute neutrophil count ≥1000/mm3, hemoglobin ≥8.5 g/dL and platelet count ≥75,000/mm3 (patients for whom < 50% of bone marrow nucleated cells are plasma cells) or ≥50,000/mm3 (patients for whom ≥50% of bone marrow nucleated cells are plasma cells).

12. Patients receiving hematopoietic growth factor support, including erythropoietin, darbepoetin, granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), and platelet stimulators (eg, eltrombopag, romiplostim, or interleukin-11) must have a 2-week interval between growth factor support and the Screening assessments, but they may receive growth factor support during the study.

13. Patients must have:

    • At least a 2-week interval from the last red blood cell (RBC) transfusion prior to the Screening hemoglobin assessment, and
    • At least a 1-week interval from the last platelet transfusion prior to the Screening platelet assessment.

However, patients may receive RBC and/or platelet transfusions as clinically indicated per institutional guidelines during the study.

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. Cancer treated with curative intent for >5 years previously and without evidence of recurrence will be allowed.

3. Has 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. Patients on prophylactic antibiotics or with a controlled infection within 1 week prior to C1D1 are acceptable.

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

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
SVd Arm: Selinexor + Bortezomib + Dexamethasone	Dexamethasone	Participants received a fixed oral dose of 100 milligrams (mg) selinexor tablets (5 tablets of 20 mg each) once weekly (QW) on Days 1, 8, 15, 22, and 29 of each 35-day cycle, along with subcutaneous (SC) injection of 1.3 milligrams per square meter (mg/m\^2) bortezomib QW on Days 1, 8, 15, and 22 of each 35-day cycle, and an oral dose of 20 mg of dexamethasone twice weekly (BIW) on Days 1, 2, 8, 9, 15, 16, 22, 23, 29, and 30 of each 35-day cycle until PD confirmed by the IRC, investigator or participant decision to discontinue study treatment, pregnancy, unacceptable AEs or toxicity that could not be managed by supportive care, withdrawal of consent, death, or sponsor decision to terminate the study.
SVd Arm: Selinexor + Bortezomib + Dexamethasone	Selinexor	Participants received a fixed oral dose of 100 milligrams (mg) selinexor tablets (5 tablets of 20 mg each) once weekly (QW) on Days 1, 8, 15, 22, and 29 of each 35-day cycle, along with subcutaneous (SC) injection of 1.3 milligrams per square meter (mg/m\^2) bortezomib QW on Days 1, 8, 15, and 22 of each 35-day cycle, and an oral dose of 20 mg of dexamethasone twice weekly (BIW) on Days 1, 2, 8, 9, 15, 16, 22, 23, 29, and 30 of each 35-day cycle until PD confirmed by the IRC, investigator or participant decision to discontinue study treatment, pregnancy, unacceptable AEs or toxicity that could not be managed by supportive care, withdrawal of consent, death, or sponsor decision to terminate the study.
SVd Arm: Selinexor + Bortezomib + Dexamethasone	Bortezomib	Participants received a fixed oral dose of 100 milligrams (mg) selinexor tablets (5 tablets of 20 mg each) once weekly (QW) on Days 1, 8, 15, 22, and 29 of each 35-day cycle, along with subcutaneous (SC) injection of 1.3 milligrams per square meter (mg/m\^2) bortezomib QW on Days 1, 8, 15, and 22 of each 35-day cycle, and an oral dose of 20 mg of dexamethasone twice weekly (BIW) on Days 1, 2, 8, 9, 15, 16, 22, 23, 29, and 30 of each 35-day cycle until PD confirmed by the IRC, investigator or participant decision to discontinue study treatment, pregnancy, unacceptable AEs or toxicity that could not be managed by supportive care, withdrawal of consent, death, or sponsor decision to terminate the study.
Vd Arm: Bortezomib + Dexamethasone	Bortezomib	Participants received SC injection of 1.3 mg/m\^2 bortezomib on Days 1, 4, 8, and 11 of each 21-day cycle for the first 8 cycles, followed by greater than or equal to (\>=) 9 cycles on Days 1, 8, 15, and 22 of each 35-day cycle, and received oral dose of 20 mg dexamethasone BIW on Days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle for the first 8 cycles and for cycles \>= 9 on Days 1, 2, 8, 9, 15, 16, 22, 23, 29, and 30 of each 35-day cycle until PD confirmed by the IRC, investigator or participant decision to discontinue study treatment, pregnancy, unacceptable AEs or toxicity that could not be managed by supportive care, withdrawal of consent, death, or sponsor decision to terminate the study.
Vd Arm: Bortezomib + Dexamethasone	Dexamethasone	Participants received SC injection of 1.3 mg/m\^2 bortezomib on Days 1, 4, 8, and 11 of each 21-day cycle for the first 8 cycles, followed by greater than or equal to (\>=) 9 cycles on Days 1, 8, 15, and 22 of each 35-day cycle, and received oral dose of 20 mg dexamethasone BIW on Days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle for the first 8 cycles and for cycles \>= 9 on Days 1, 2, 8, 9, 15, 16, 22, 23, 29, and 30 of each 35-day cycle until PD confirmed by the IRC, investigator or participant decision to discontinue study treatment, pregnancy, unacceptable AEs or toxicity that could not be managed by supportive care, withdrawal of consent, death, or sponsor decision to terminate the study.
SVdX Arm: Selinexor + Bortezomib + Dexamethasone	Dexamethasone	Participants in the VD arm who had IRC-confirmed PD and were able to tolerate continued bortezomib treatment had crossed over to receive fixed oral dose of 100 mg selinexor tablets (5 tablets of 20 mg each) QW on Days 1, 8, 15, 22, and 29 of each 35-day cycle, along with SC injection of 1.3 mg/m\^2 bortezomib QW on Days 1, 8, 15, and 22 of each 35-day cycle, and an oral dose of 20 mg of dexamethasone BIW on Days 1, 2, 8, 9, 15, 16, 22, 23, 29, and 30 of each 35-day cycle until PD confirmed by the IRC, investigator or participant decision to discontinue study treatment, pregnancy, unacceptable AEs or toxicity that could not be managed by supportive care, withdrawal of consent, death, or sponsor decision to terminate the study.
SVdX Arm: Selinexor + Bortezomib + Dexamethasone	Selinexor	Participants in the VD arm who had IRC-confirmed PD and were able to tolerate continued bortezomib treatment had crossed over to receive fixed oral dose of 100 mg selinexor tablets (5 tablets of 20 mg each) QW on Days 1, 8, 15, 22, and 29 of each 35-day cycle, along with SC injection of 1.3 mg/m\^2 bortezomib QW on Days 1, 8, 15, and 22 of each 35-day cycle, and an oral dose of 20 mg of dexamethasone BIW on Days 1, 2, 8, 9, 15, 16, 22, 23, 29, and 30 of each 35-day cycle until PD confirmed by the IRC, investigator or participant decision to discontinue study treatment, pregnancy, unacceptable AEs or toxicity that could not be managed by supportive care, withdrawal of consent, death, or sponsor decision to terminate the study.
SVdX Arm: Selinexor + Bortezomib + Dexamethasone	Bortezomib	Participants in the VD arm who had IRC-confirmed PD and were able to tolerate continued bortezomib treatment had crossed over to receive fixed oral dose of 100 mg selinexor tablets (5 tablets of 20 mg each) QW on Days 1, 8, 15, 22, and 29 of each 35-day cycle, along with SC injection of 1.3 mg/m\^2 bortezomib QW on Days 1, 8, 15, and 22 of each 35-day cycle, and an oral dose of 20 mg of dexamethasone BIW on Days 1, 2, 8, 9, 15, 16, 22, 23, 29, and 30 of each 35-day cycle until PD confirmed by the IRC, investigator or participant decision to discontinue study treatment, pregnancy, unacceptable AEs or toxicity that could not be managed by supportive care, withdrawal of consent, death, or sponsor decision to terminate the study.
SdX Arm: Selinexor + Dexamethasone	Selinexor	Participants in the VD arm who had IRC-confirmed PD and were unable to tolerate continued bortezomib treatment had crossed over to receive fixed oral dose of 100 mg selinexor tablets (5 tablets of 20 mg each) QW on Days 1, 8, 15, 22, and 29 of each 35-day cycle and an oral dose of 20 mg of dexamethasone BIW on Days 1, 2, 8, 9, 15, 16, 22, 23, 29, and 30 of each 35-day cycle until PD confirmed by the IRC, investigator or participant decision to discontinue study treatment, pregnancy, unacceptable AEs or toxicity that could not be managed by supportive care, withdrawal of consent, death, or sponsor decision to terminate the study.
SdX Arm: Selinexor + Dexamethasone	Dexamethasone	Participants in the VD arm who had IRC-confirmed PD and were unable to tolerate continued bortezomib treatment had crossed over to receive fixed oral dose of 100 mg selinexor tablets (5 tablets of 20 mg each) QW on Days 1, 8, 15, 22, and 29 of each 35-day cycle and an oral dose of 20 mg of dexamethasone BIW on Days 1, 2, 8, 9, 15, 16, 22, 23, 29, and 30 of each 35-day cycle until PD confirmed by the IRC, investigator or participant decision to discontinue study treatment, pregnancy, unacceptable AEs or toxicity that could not be managed by supportive care, withdrawal of consent, death, or sponsor decision to terminate the study.

Primary Outcome Measures

Name	Time	Method
SVd/Vd Arm: Progression-free Survival (PFS) as Assessed by Independent Review Committee (IRC)	From date of randomization until IRC-confirmed documented PD or death, censored date, whichever occurred first (up to 33 months)	PFS was defined as time from date of randomization until the first date of IRC-confirmed PD, per International Myeloma Working Group (IMWG) response criteria, or death due to any cause, whichever occurs first. PD included increase of 25% from lowest confirmed response value in 1 or more of the following criteria: a) serum M-protein with absolute increase of \>= 0.5 gram per deciliter (g/dL); b) serum M-protein increase \>= 1 g/dL if the lowest M-component was \>=5 g/dL; c) urine M-protein (absolute increase must be \>= 200 mg per 24 hours); d) in participants without measurable serum and urine M-protein levels: the difference between involved and uninvolved free light chain (FLC) levels (absolute increase must be greater than \[\>\] 10 mg/dL); e) in participants without measurable serum and urine M-protein levels and without measurable involved FLC levels: bone marrow plasma cell percentage irrespective of baseline status (absolute increase must be \>=10%).

Secondary Outcome Measures

Name	Time	Method
SVd/Vd Arm: Number of Participants With at Least One Grade Greater Than or Equal to [>=] 2 Peripheral Neuropathy Events	From first dose of study treatment to 30 days after the last dose of study treatment inclusive, or the day before the start of new anti-MM treatment, whichever occurs first (up to 33 months)	Peripheral neuropathy events was assessed using the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03. The grade ranges from Grade 1 (mild, asymptomatic, or mild symptoms) to Grade 5 (death related to an adverse event). Grade 2 indicates a moderate condition that may require minimal intervention and can limit certain daily activities. Grade 3 represents severe symptoms that are not immediately life-threatening but may lead to hospitalization and restrict self-care activities. Grade 4 denotes life-threatening consequences requiring urgent intervention. Number of participants experiencing at least one Grade \>= 2 peripheral neuropathy event have been reported.
SVdX Arm: Overall Response Rate (ORR1) as Assessed by IRC During SVdX Treatment	From date of first SVdX treatment until disease progression or initiating a new MM treatment (up to 33 months)	ORR was defined as the percentage of the participants who achieved a confirmed partial response or better (i.e., PR, VGPR, CR, or sCR) based on the IRC's response outcome assessments, according to the IMWG response criteria. PR: \>=50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by \>=90% or \<200 mg per 24 hours; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level \<100 mg per 24 hours; CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \<=5% plasma cells in bone marrow; or sCR: CR as defined as Normal FLC ratio+ Absence of clonal cells in bone marrow biopsy by immunohistochemistry.
SVdX Arm: Progression Free Survival1 (PFS1) as Assessed by IRC During SVdX Treatment	From date of first SVdX treatment until IRC-confirmed documented PD or death or censored date, whichever occurred first (up to 33 months)	PFS1 is defined as the duration of time from the date of the first dose of the SVd treatment after crossover from the Vd arm until the first date of PD or death due to any cause, whichever occurred first. PD included increase of 25% from lowest confirmed response value in 1 or more of the following criteria: a) serum M-protein with absolute increase of \>= 0.5 gram per deciliter (g/dL); b) serum M-protein increase \>= 1 g/dL if the lowest M-component was \>=5 g/dL; c) urine M-protein (absolute increase must be \>= 200 mg per 24 hours); d) in participants without measurable serum and urine M-protein levels: the difference between involved and uninvolved free light chain (FLC) levels (absolute increase must be greater than \[\>\] 10 mg/dL); e) in participants without measurable serum and urine M-protein levels and without measurable involved FLC levels: bone marrow plasma cell percentage irrespective of baseline status (absolute increase must be \>=10%).
SVd/Vd Arm: Percentage of Participants With Response Rate of Very Good Partial Response (VGPR) or Better Based on IRC Assessment	From date of randomization until confirmed PD or initiating a new MM treatment (up to 33 months)	Response rate was defined as percentage of participants with responses of VGPR, at any time prior to IRC-confirmed PD or initiating a new MM treatment. VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level \< 100 mg per 24 hours.
SVd/Vd Arm: Overall Response Rate (ORR) as Assessed by IRC	From date of randomization until disease progression or initiating a new MM treatment (up to 33 months)	ORR was defined as the percentage of the participants who achieved any confirmed partial response (PR) or better PR, complete response (CR), very good partial response (VGPR) or stringent complete response (sCR) based on the IRC's response outcome assessments, according to the International Myeloma Working Group (IMWG) response criteria, before IRC-confirmed PD or initiating a new MM treatment. PR: \>= 50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by \>= 90% or to \< 200 mg per 24 hours; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level \< 100 mg per 24 hours; CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \<= 5% plasma cells in bone marrow; or stringent complete response (sCR): CR as defined as Normal free light chain (FLC) ratio + Absence of clonal cells by immunohistochemistry.
SVd/Vd Arm: Overall Survival (OS)	From date of randomization to the date of death or censored date, whichever occurred first (up to 45 months)	OS was defined as the time from the date of randomization until either the date of death due to any cause or until the participant is lost to follow-up, for all participants.
SVd/Vd Arm: Duration of Response (DOR) as Assessed by IRC	From the first documentation of response to the first documentation of PD or death, whichever occurred first (up to 45 months)	DOR was defined as the duration of time from the first occurrence of an IRC confirmed response of at least (\>=) PR until the first date of IRC-confirmed PD or death due to any cause, whichever occurred first. PR: \>= 50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by \>= 90% or to \< 200 mg per 24 hours; PD: Increase of 25% from lowest confirmed response value in 1 or more of the following criteria: Serum M-protein with absolute increase of \>= 0.5 g/dL; Serum M-protein increase \>= 1 g/dL if the lowest M-component was \>= 5 g/dL; Urine M-protein (absolute increase must be \>= 200 mg per 24 hours). Analysis was performed using Kaplan-Meier method.
SVd/Vd Arm: Time-to-next-treatment (TTNT) in Participants Randomized to the SVd and Vd Arm Who Received Treatment After SVd/Vd	From date of randomization to start of next anti-MM treatment or death, whichever occurred first (up to 33 months)	TTNT is defined as the duration from date of randomization to start of next anti-MM treatment or death, whichever occurs first. For patients without an event, their follow-up time will be censored at the date of discontinuation from study, or last participating visit on or before database cutoff date, whichever occurs first.
SVd/Vd Arm: Time To Response (TTR) in Participants Randomized to the SVd and Vd Arm	From randomization to the date of first IRC-confirmed PR or better (i.e., PR, VGPR, CR, or sCR), whichever occurred first (up to 33 months)	TTR was defined as duration from randomization to the date of first IRC-confirmed PR or better (i.e., PR, VGPR, CR, or sCR) before IRC-confirmed PD or initiating a new MM treatment per IMWG response criteria. The participants who do not achieve IRC-confirmed PR or better response will be censored at the date of last disease assessment on or before database cutoff date. PR: \>= 50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by \>= 90% or to \< 200 mg per 24 hours; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level \< 100 mg per 24 hours; CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \<= 5% plasma cells in bone marrow; or sCR: Normal free light chain (FLC) ratio + Absence of clonal cells by immunohistochemistry.
SVd/Vd/SVdx Arm: Progression Free Survival 2 (PFS 2) in Participants Randomized to the SVd and Vd Arm Who Received Post-SVd/Vd/SVdX Treatment	From date of first dose of post-SVd/Vd/SVdX treatment to the date of first PD on post-SVd/Vd/SVdX treatment, or death due to any cause (up to 33 months)	PFS 2 was defined as the duration of time from the date of the first dose of the treatment after SVd/Vd/SVdX until the first date of PD on treatment after SVd/Vd/SVdX or death due to any cause, whichever occurred first. PD included increase of 25% from lowest confirmed response value in 1 or more of the following criteria: a) serum M-protein with absolute increase of \>= 0.5 gram per deciliter (g/dL); b) serum M-protein increase \>= 1 g/dL if the lowest M-component was \>=5 g/dL; c) urine M-protein (absolute increase must be \>= 200 mg per 24 hours); d) in participants without measurable serum and urine M-protein levels: the difference between involved and uninvolved free light chain (FLC) levels (absolute increase must be greater than \[\>\] 10 mg/dL); e) in participants without measurable serum and urine M-protein levels and without measurable involved FLC levels: bone marrow plasma cell percentage irrespective of baseline status (absolute increase must be \>=10%).
SVd/Vd Arm: Change From Baseline in Participant-Reported Peripheral Neuropathy (PN) Assessed by European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire- Chemotherapy-Induced PN 20 (EORTC- QLQ-CIPN20) Total Scores	Svd Arm: Baseline up to End of treatment (EOT) (at Day 820); Vd Arm: Baseline up to EOT (at Day 848)	The EORTC QLQ-CIPN20 instrument is a 20-item QoL instrument, which has been developed to elicit patients' experience of symptoms and functional limitations related to CIPN. The QLQ-CIPN20 contains 20 items assessing sensory (9 items), motor (8 items), and autonomic symptoms (3 items) containing a 4-point Likert scale (1= not at all, 2= a little, 3= quite a bit, and 4= very much), participants indicate the degree to which they have experienced sensory, motor, and autonomic symptoms during the past week. Sensory raw scale scores range from 1 to 36, motor raw scale scores range from 1 to 32, and autonomic raw scale scores range from 1 to 12 for men and 1-8 for women (erectile function item is excluded). All scale scores are linearly converted to a total score with range of 0-100 scale, with higher scores indicating more symptom burden.

Trial Locations

Locations (156)

Princess Margaret Cancer Research; 🇨🇦 Toronto, Ontario, Canada

Kaiser Permanente Hawaii; 🇺🇸 Honolulu, Hawaii, United States

Norton Cancer Institute; 🇺🇸 Louisville, Kentucky, United States

G. Kuppuswamy Naidu Hospital; 🇮🇳 Coimbatore, Tamil Nadu, India

McFarland Clinic; 🇺🇸 Ames, Iowa, United States

Stormont Vail Health Care (Cotton O'Neil Cancer Center ); 🇺🇸 Topeka, Kansas, United States

Central Care Cancer Center; 🇺🇸 Bolivar, Missouri, United States

The Valley Hospital Luckow Pavilion; 🇺🇸 Paramus, New Jersey, United States

Calvary Mater Newcastle; 🇦🇺 Waratah, New South Wales, Australia

St. Vincent's Hospital Melbourne; 🇦🇺 Fitzroy, Victoria, Australia

University Multiprofile Hospital for Active Treatment, Sveti Georgi Clinic of Clinical Hematology; 🇧🇬 Plovdiv, Bulgaria

Tom Baker Cancer Center/ Alberta Health Services; 🇨🇦 Calgary, Alberta, Canada

Vancouver General Hospital; 🇨🇦 Vancouver, British Columbia, Canada

L'Hôtel-Dieu de Québec; 🇨🇦 Quebec City, Quebec, Canada

General University Hospital in Prague; 🇨🇿 Praha 2, Prague, Czechia

University Hopsital Brno; 🇨🇿 Brno, Czechia

University Hospital Hradec Kralove; 🇨🇿 Hradec Kralove, Czechia

University Hospital Olomouc; 🇨🇿 Olomouc, Czechia

University Hospital Kralovske Vinohrady, Clinic of Internal Hematology; 🇨🇿 Prague, Czechia

University Hospital Ostrava, Dept. of Hematooncology; 🇨🇿 Ostrava, Czechia

Hospital Center Departmental La Roche-Sur-Yon; 🇫🇷 La Roche-sur-Yon, France

Miletrie Hospital, University Hospital Center of Poitiers; 🇫🇷 Poitiers, France

Claude Huriez Hospital; 🇫🇷 Lille, France

Nantes University Hospital Center; 🇫🇷 Nantes, France

Saint-Louis Hospital; 🇫🇷 Paris, France

University Hospital Freiburg, Department of Internal Medicine I; 🇩🇪 Freiburg, Baden-Wuerttemberg, Germany

General Hospital of Athens "Evangelismos", Department of Hematology and Lymphoma; 🇬🇷 Athens, Greece

Alexandra General Hospital, Therapeutic Clinic; 🇬🇷 Athens, Greece

University General Hospital of Patra; 🇬🇷 Pátra, Greece

Theageneion Cancer Hospital, Hematology Department; 🇬🇷 Thessaloníki, Greece

Semmelweis University, 1st Department of Internal Medicine; 🇭🇺 Budapest, Hungary

Semmelweis University, 3rd Department of Internal Medicine; 🇭🇺 Budapest, Hungary

Kaposi Mor Teaching Hospital, 2nd Department of Internal Medicine; 🇭🇺 Kaposvar, Hungary

Prince Aly Khan Hospital; 🇮🇳 Mumbai, Maharashta, India

Medical Center of the University of Pecs, Department of Hematology; 🇭🇺 Pecs, Hungary

Regional Cancer Centre; 🇮🇳 Thiruvananthapuram, Kerala, India

Bhaktivedanta Hospital; 🇮🇳 Thane, Maharashtra, India

Postgraduate Institute of Medical Education & Research (PGIMER); 🇮🇳 Chandigarh, Punjab, India

Dayanand Medical College & Hospital; 🇮🇳 Ludhiana, Punjab, India

SRM Institute of Medical Sciences; 🇮🇳 Chennai, Tamil Nadu, India

Saveetha Medical College Hospital; 🇮🇳 Chennai, Tamil Nadu, India

Asviratham Speciality Hospital; 🇮🇳 Madurai, Tamil Nadu, India

Yashoda Hospital; 🇮🇳 Hyderabad, Telengana, India

Meenakshi Mission Hospital; 🇮🇳 Madurai, Tamil Nadu, India

King George's Medical University; 🇮🇳 Lucknow, Uttar Pradesh, India

TATA Memorial Centre; 🇮🇳 Kolkata, West Bengal, India

Barzilai Medical Center; 🇮🇱 Ashkelon, Israel

Hadassah Medical Center; 🇮🇱 Jerusalem, Israel

Rambam Health Care Campus; 🇮🇱 Haifa, Israel

Rabin Medical Center; 🇮🇱 Petaẖ Tiqwa, Israel

ASST Papa Giovanni XXIII; 🇮🇹 Bergamo, Italy

Azienda Ospedaliero-Universitaria Ospedali Riuniti; 🇮🇹 Ancona, Italy

Polyclinic S. Orsola-Malpighi, Department of Hematology, Oncology and Laboratory Medicine, Operative Unit of Hematology - Cavo; 🇮🇹 Bologna, Italy

University Hospital San Martino, IRCCA, Dept. of Integrative Cancer Therapies, Operative Unit of Clinical Hematology; 🇮🇹 Genoa, Italy

University Hospital San Giovanni Battista of Turin; 🇮🇹 Turin, Italy

Jan Biziel University Hospital #2 in Bydgoszcz, Department of Hematology; 🇵🇱 Bydgoszcz, Poland

Independent Public Teaching Hospital No.1 in Lublin, Department of Hematology-Oncology and Bone Marrow Transplantation; 🇵🇱 Lublin, Poland

University Hospital in Krakow, Teaching Unit of the Hematology Department; 🇵🇱 Krakow, Poland

Military Institute of Medicine, Department of Internal Medicine and Hematology; 🇵🇱 Warsaw, Poland

St. John of Dukla Oncology Center of Lublin, Department of Hematology; 🇵🇱 Lublin, Poland

Nicolaus Copernicus Memorial Provincial Specialist Hospital in Lodz, Department of Hematology; 🇵🇱 Łódź, Poland

Hyperclnical MedLife PDR Vulturului Brasov, Hematology Department; 🇷🇴 Braşov, Romania

Colentina Clinical Hospital, Department of Hematology; 🇷🇴 Bucharest, Romania

Bucharest University Emergency Hospital, Department of Hematology; 🇷🇴 Bucharest, Romania

N.A. Semashko Central Clinical Hospital #2 under OJSC Russian Railways; 🇷🇺 Moscow, Russian Federation

S.P. Botkin City Clinical Hospital; 🇷🇺 Moscow, Russian Federation

V.A. Almazov North-West Federal Medical Research Center, Chemotherapy of Oncohematology Diseases and Bone Marrow Transplantation Department #1; 🇷🇺 Saint Petersburg, Russian Federation

First I.P. Pavlov State Medical University of St. Petersburg; 🇷🇺 Saint Petersburg, Russian Federation

Clinical Center of Serbia, Clinic of Hematology; 🇷🇸 Belgrade, Serbia

Institute of Oncology and Radiology of Serbia, Clinic of Medical Oncology; 🇷🇸 Belgrade, Serbia

Clinical Center Nis, Clinic of Hematology and Clinical Immunology; 🇷🇸 Nis, Serbia

Catalan Institute of Oncology (ICO) Badalona; 🇪🇸 Badalona, Spain

Clinical Center of Vojvodina, Clinic of Hematology; 🇷🇸 Novi Sad, Serbia

Cherkasy Regional Oncology Center, Regional Treatment and Diagnostic Hematology Center, Department of Hematology; 🇺🇦 Cherkasy, Ukraine

University Hospital Infanta Leonor, Department of Hematology; 🇪🇸 Madrid, Spain

University Hospital of Vall d'Hebron; 🇪🇸 Barcelona, Spain

University Clinical Hospital of Salamanca, Department of Hematology; 🇪🇸 Salamanca, Spain

BMT Kiev Center; 🇺🇦 Kiev, Ukraine

Kiev Cancer Institute; 🇺🇦 Kiev, Ukraine

O.F. Herbachevskyi Regional Clinical Hospital, Hematology Department with Intensive Therapy Wards; 🇺🇦 Zhytomyr, Ukraine

Cardiff & Vale University Health Board University Hospital of Wales; 🇬🇧 Cardiff, Wales, United Kingdom

NHS Tayside Ninewells Hospital; 🇬🇧 Dundee, Scotland, United Kingdom

University Hospitals Birmingham NHS Foundation Trust Queen Elizabeth Hospital; 🇬🇧 Birmingham, United Kingdom

Royal Liverpool & Broadgreen University Hospital NHS Trust Royal Liverpool University Hospital; 🇬🇧 Liverpool, United Kingdom

London North West Healthcare NHS Trust Northwick Park Hospital; 🇬🇧 London, United Kingdom

King's College Hospital NHS Foundation Trust; 🇬🇧 London, United Kingdom

Imperial College Healthcare NHS Trust Hammersmith Hospital; 🇬🇧 London, United Kingdom

The Christie NHS Foundation Trust; 🇬🇧 Manchester, United Kingdom

Freeman Hospital; 🇬🇧 Newcastle Upon Tyne, United Kingdom

The Royal Wolverhampton NHS Trust New Cross Hospital; 🇬🇧 Wolverhampton, United Kingdom

University Hospital of the Canary Islands; 🇪🇸 La Laguna, Santa Cruz De Tenerife, Spain

Hospital Santa Maria of Terni; 🇮🇹 Terni, Umbria, Italy

Cancer Institute; 🇮🇳 Chennai, Tamil Nadu, India

Emory University; 🇺🇸 Atlanta, Georgia, United States

Commonwealth Hematology; 🇺🇸 Danville, Kentucky, United States

University of Cincinnati Health; 🇺🇸 Cincinnati, Ohio, United States

Mount Sinai; 🇺🇸 New York, New York, United States

The Cancer Institute at St. Francis Hospital; 🇺🇸 Roslyn, New York, United States

Southwest Cancer Center of Oklahoma; 🇺🇸 Lawton, Oklahoma, United States

Baylor Sammons Cancer Center; 🇺🇸 Dallas, Texas, United States

University of Texas Southwestern; 🇺🇸 Dallas, Texas, United States

Rajiv Gandhi Cancer Hospital; 🇮🇳 New Delhi, India

University Hospital Careggi, Department of Hematology; 🇮🇹 Florence, Italy

City Clinical Hospital No.4 of Dnipro City Council, City hematology center; 🇺🇦 Dnipropetrovsk, Ukraine

Cross Cancer Institute / University of Alberta; 🇨🇦 Edmonton, Alberta, Canada

Queen Elizabeth II Health Sciences Center; 🇨🇦 Halifax, Nova Scotia, Canada

Netaji Subhash Chandra Bose Cancer Research Institute; 🇮🇳 Kolkata, West Bengal, India

SCOR AnMed Health Cancer Center; 🇺🇸 Anderson, South Carolina, United States

Boca Raton Clinical Research (BRCR) Medical Center; 🇺🇸 Plantation, Florida, United States

University Hospital Krems, Department of Internal Medicine II; 🇦🇹 Krems, Austria

Medical University of Vienna; 🇦🇹 Vienna, Austria

UCL Saint-Luc; 🇧🇪 Brussels, Belgium

Specialized Hospital for Active Treatment of Hematological Diseases, Clinic of Hematology, Dept. of Clinical Hematology; 🇧🇬 Sofia, Bulgaria

Royal Victoria Hospital / McGill University; 🇨🇦 Montreal, Quebec, Canada

Institute of Blood Pathology and Transfusion Medicine, Department of Hematology with Laboratory Group; 🇺🇦 Lviv, Ukraine

Group Practice for Hematology and Oncology; 🇩🇪 Dresden, Saxony, Germany

Nil Ratan Sircar (NRS) Medical College; 🇮🇳 Kolkata, West Bengal, India

General Hospital Hietzing; 🇦🇹 Vienna, Austria

Wilhelminen Hospital, Department of Internal Medicine I, Center for Oncology & Hematology; 🇦🇹 Vienna, Austria

University Hospital Ghent; 🇧🇪 Ghent, Belgium

General Hospital Delta; 🇧🇪 Roeselare, Belgium

University of Maryland; 🇺🇸 Baltimore, Maryland, United States

The Alfred Hospital; 🇦🇺 Melbourne, Victoria, Australia

Mater Misericordiae Limited and Mater Medical Research; 🇦🇺 South Brisbane, Queensland, Australia

Royal Brisbane and Women's Hospital; 🇦🇺 Herston, Queensland, Australia

Prairie Lakes Healthcare; 🇺🇸 Watertown, South Dakota, United States

Jules Bordet Institute; 🇧🇪 Brussels, Belgium

Necker Children's Hospital, Department of Adult Hematology; 🇫🇷 Paris, Ile De France, France

Brabois Adults Hospital, University Hospital Center of Nancy; 🇫🇷 Nancy, France

Klinikum Leverkusen gGmbH Medizinisxhe Klinik 3; 🇩🇪 Leverkusen, North Rhine Westfalia, Germany

Umberto I Polyclinic of Rome, Department of Cellular Biotechnology and Hematology, Hematology Center; 🇮🇹 Rome, Italy

Independent Public Healthcare Facility Municipal Hospital Group in Chorzow, Department of Hematology; 🇵🇱 Chorzow, Poland

Clinical Center Kragujevac, Clinic of Hematology; 🇷🇸 Kragujevac, Serbia

Saskatchewan Cancer Agency-Allan Blair Cancer Centre; 🇨🇦 Regina, Saskatchewan, Canada

Gold Coast University Hospital; 🇦🇺 Southport, Queensland, Australia

Medical University Innsbruck, Department of Internal Medicine V (Hematology and Oncology); 🇦🇹 Innsbruck, Austria

St. Augustinus Hospital; 🇧🇪 Wilrijk, Belgium

University Multiprofile Hospital for Active Treatment, Sveti Ivan Rilski Clinic of Hematology; 🇧🇬 Sofia, Bulgaria

Maisonneuve-Rosemont Hospital; 🇨🇦 Montreal, Quebec, Canada

Jaslok Hospital and Research Centre; 🇮🇳 Mumbai, Maharashta, India

Flinders Medical Centre; 🇦🇺 Bedford Park, South Australia, Australia

North East Cancer Centre Sudbury; 🇨🇦 Sudbury, Ontario, Canada

Royal Adelaide Hospital; 🇦🇺 Adelaide, South Australia, Australia

Vinnytsia M.I. Pyrohov Regional Clinical Hospital, Department of Hematology; 🇺🇦 Vinnytsia, Ukraine

IMS & SUM Hospital; 🇮🇳 Bhubaneswar, Odisha, India

Integrated Szent Istvan and Szent laszlo Hospital, Department of Hematology and Stem Cell Transplantation; 🇭🇺 Budapest, Hungary

South Lyon Hospital Center; 🇫🇷 Lyon, France

Belfast Heatlh & Social Care Trust Belfast City Hospital; 🇬🇧 Belfast, Northern Ireland, United Kingdom

Hospital Niguerda Ca Granda, Department of Hematology and Oncology, Hematology Unit; 🇮🇹 Milan, Italy

University Hospital Virgen del Rocio (HUVR); 🇪🇸 Seville, Spain

Kaiser Permanente Northwest OR; 🇺🇸 Portland, Oregon, United States

The Leeds Teaching Hospitals NHS Trust St. James University Hospital; 🇬🇧 Leeds, United Kingdom

University Hospitals of Leicester NHS Trust Royal Leicester Infirmary; 🇬🇧 Leicester, United Kingdom

University College London; 🇬🇧 London, United Kingdom

Novant-Forsyth Memorial Hospital; 🇺🇸 Winston-Salem, North Carolina, United States

Saskatoon Cancer Center; 🇨🇦 Saskatoon, Saskatchewan, Canada