Bortezomib, Selinexor, and Dexamethasone in Patients With Multiple Myeloma

Multiple Myeloma Clinical Trial

— BOSTON  

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03110562
• Other study ID #: KCP-330-023
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: May 24, 2017
• Est. completion date: September 1, 2023

Study information

• Verified date: January 2023
• Source: Karyopharm Therapeutics Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 402
• Est. completion date: September 1, 2023
• Est. primary completion date: February 18, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Selinexor
oral 100 mg dose
• Bortezomib
subcutaneous dose of 1.3 mg/m2
• Dexamethasone
oral dose of 20mg

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Flinders Medical Centre	Bedford Park	South Australia
Australia	St. Vincent's Hospital Melbourne	Fitzroy	Victoria
Australia	Royal Brisbane and Women's Hospital	Herston	Queensland
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	Mater Misericordiae Limited and Mater Medical Research	South Brisbane	Queensland
Australia	Gold Coast University Hospital	Southport	Queensland
Australia	Calvary Mater Newcastle	Waratah	New South Wales
Austria	Medical University Innsbruck, Department of Internal Medicine V (Hematology and Oncology)	Innsbruck
Austria	University Hospital Krems, Department of Internal Medicine II	Krems
Austria	General Hospital Hietzing	Vienna
Austria	Medical University of Vienna	Vienna
Austria	Wilhelminen Hospital, Department of Internal Medicine I, Center for Oncology & Hematology	Vienna
Belgium	Jules Bordet Institute	Brussels
Belgium	UCL Saint-Luc	Brussels
Belgium	University Hospital Ghent	Ghent
Belgium	General Hospital Delta	Roeselare
Belgium	St. Augustinus Hospital	Wilrijk
Bulgaria	University Multiprofile Hospital for Active Treatment, Sveti Georgi Clinic of Clinical Hematology	Plovdiv
Bulgaria	Specialized Hospital for Active Treatment of Hematological Diseases, Clinic of Hematology, Dept. of Clinical Hematology	Sofia
Bulgaria	University Multiprofile Hospital for Active Treatment, Sveti Ivan Rilski Clinic of Hematology	Sofia
Canada	Tom Baker Cancer Center/ Alberta Health Services	Calgary	Alberta
Canada	Cross Cancer Institute / University of Alberta	Edmonton	Alberta
Canada	Queen Elizabeth II Health Sciences Center	Halifax	Nova Scotia
Canada	Maisonneuve-Rosemont Hospital	Montreal	Quebec
Canada	Royal Victoria Hospital / McGill University	Montreal	Quebec
Canada	L'Hôtel-Dieu de Québec	Quebec City	Quebec
Canada	Saskatchewan Cancer Agency-Allan Blair Cancer Centre	Regina	Saskatchewan
Canada	Saskatoon Cancer Center	Saskatoon	Saskatchewan
Canada	North East Cancer Centre Sudbury	Sudbury	Ontario
Canada	Princess Margaret Cancer Research	Toronto	Ontario
Canada	Vancouver General Hospital	Vancouver	British Columbia
Czechia	University Hopsital Brno	Brno
Czechia	University Hospital Hradec Kralove	Hradec Kralove
Czechia	University Hospital Olomouc	Olomouc
Czechia	University Hospital Ostrava, Dept. of Hematooncology	Ostrava
Czechia	University Hospital Kralovske Vinohrady, Clinic of Internal Hematology	Prague
Czechia	General University Hospital in Prague	Praha 2	Prague
France	Hospital Center Departmental La Roche-Sur-Yon	La Roche-sur-Yon
France	Claude Huriez Hospital	Lille
France	South Lyon Hospital Center	Lyon
France	Brabois Adults Hospital, University Hospital Center of Nancy	Nancy
France	Nantes University Hospital Center	Nantes
France	Necker Children's Hospital, Department of Adult Hematology	Paris	Ile De France
France	Saint-Louis Hospital	Paris
France	Miletrie Hospital, University Hospital Center of Poitiers	Poitiers
Germany	Group Practice for Hematology and Oncology	Dresden	Saxony
Germany	University Hospital Freiburg, Department of Internal Medicine I	Freiburg	Baden-Wuerttemberg
Germany	Klinikum Leverkusen gGmbH Medizinisxhe Klinik 3	Leverkusen	North Rhine Westfalia
Greece	Alexandra General Hospital, Therapeutic Clinic	Athens
Greece	General Hospital of Athens "Evangelismos", Department of Hematology and Lymphoma	Athens
Greece	University General Hospital of Patra	Pátra
Greece	Theageneion Cancer Hospital, Hematology Department	Thessaloníki
Hungary	Integrated Szent Istvan and Szent laszlo Hospital, Department of Hematology and Stem Cell Transplantation	Budapest
Hungary	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	Medical Center of the University of Pecs, Department of Hematology	Pecs
India	IMS & SUM Hospital	Bhubaneswar	Odisha
India	Postgraduate Institute of Medical Education & Research (PGIMER)	Chandigarh	Punjab
India	Cancer Institute	Chennai	Tamil Nadu
India	Saveetha Medical College Hospital	Chennai	Tamil Nadu
India	SRM Institute of Medical Sciences	Chennai	Tamil Nadu
India	G. Kuppuswamy Naidu Hospital	Coimbatore	Tamil Nadu
India	Yashoda Hospital	Hyderabad	Telengana
India	Netaji Subhash Chandra Bose Cancer Research Institute	Kolkata	West Bengal
India	Nil Ratan Sircar (NRS) Medical College	Kolkata	West Bengal
India	TATA Memorial Centre	Kolkata	West Bengal
India	King George's Medical University	Lucknow	Uttar Pradesh
India	Dayanand Medical College & Hospital	Ludhiana	Punjab
India	Asviratham Speciality Hospital	Madurai	Tamil Nadu
India	Meenakshi Mission Hospital	Madurai	Tamil Nadu
India	Jaslok Hospital and Research Centre	Mumbai	Maharashta
India	Prince Aly Khan Hospital	Mumbai	Maharashta
India	Rajiv Gandhi Cancer Hospital	New Delhi
India	Regional Cancer Centre	Patna	Bihar
India	Bhaktivedanta Hospital	Thane	Maharashtra
India	Regional Cancer Centre	Thiruvananthapuram	Kerala
Israel	Barzilai Medical Center	Ashkelon
Israel	Rambam Health Care Campus	Haifa
Israel	Hadassah Medical Center	Jerusalem
Israel	Rabin Medical Center	Peta? Tiqwa
Italy	Azienda Ospedaliero-Universitaria Ospedali Riuniti	Ancona
Italy	ASST Papa Giovanni XXIII	Bergamo
Italy	Polyclinic S. Orsola-Malpighi, Department of Hematology, Oncology and Laboratory Medicine, Operative Unit of Hematology - Cavo	Bologna
Italy	University Hospital Careggi, Department of Hematology	Florence
Italy	University Hospital San Martino, IRCCA, Dept. of Integrative Cancer Therapies, Operative Unit of Clinical Hematology	Genoa
Italy	Hospital Niguerda Ca Granda, Department of Hematology and Oncology, Hematology Unit	Milan
Italy	Umberto I Polyclinic of Rome, Department of Cellular Biotechnology and Hematology, Hematology Center	Rome
Italy	Hospital Santa Maria of Terni	Terni	Umbria
Italy	University Hospital San Giovanni Battista of Turin	Turin
Poland	Jan Biziel University Hospital #2 in Bydgoszcz, Department of Hematology	Bydgoszcz
Poland	Independent Public Healthcare Facility Municipal Hospital Group in Chorzow, Department of Hematology	Chorzow
Poland	University Hospital in Krakow, Teaching Unit of the Hematology Department	Krakow
Poland	Nicolaus Copernicus Memorial Provincial Specialist Hospital in Lodz, Department of Hematology	Lódz
Poland	Independent Public Teaching Hospital No.1 in Lublin, Department of Hematology-Oncology and Bone Marrow Transplantation	Lublin
Poland	St. John of Dukla Oncology Center of Lublin, Department of Hematology	Lublin
Poland	Military Institute of Medicine, Department of Internal Medicine and Hematology	Warsaw
Romania	Hyperclnical MedLife PDR Vulturului Brasov, Hematology Department	Brasov
Romania	Bucharest University Emergency Hospital, Department of Hematology	Bucharest
Romania	Colentina Clinical Hospital, Department of Hematology	Bucharest
Russian Federation	N.A. Semashko Central Clinical Hospital #2 under OJSC Russian Railways	Moscow
Russian Federation	S.P. Botkin City Clinical Hospital	Moscow
Russian Federation	First I.P. Pavlov State Medical University of St. Petersburg	Saint Petersburg
Russian Federation	V.A. Almazov North-West Federal Medical Research Center, Chemotherapy of Oncohematology Diseases and Bone Marrow Transplantation Department #1	Saint Petersburg
Serbia	Clinical Center of Serbia, Clinic of Hematology	Belgrade
Serbia	Institute of Oncology and Radiology of Serbia, Clinic of Medical Oncology	Belgrade
Serbia	Clinical Center Kragujevac, Clinic of Hematology	Kragujevac
Serbia	Clinical Center Nis, Clinic of Hematology and Clinical Immunology	Nis
Serbia	Clinical Center of Vojvodina, Clinic of Hematology	Novi Sad
Spain	Catalan Institute of Oncology (ICO) Badalona	Badalona
Spain	University Hospital of Vall d'Hebron	Barcelona
Spain	University Hospital of the Canary Islands	La Laguna	Santa Cruz De Tenerife
Spain	University Hospital Infanta Leonor, Department of Hematology	Madrid
Spain	University Clinical Hospital of Salamanca, Department of Hematology	Salamanca
Spain	University Hospital Virgen del Rocio (HUVR)	Seville
Ukraine	Cherkasy Regional Oncology Center, Regional Treatment and Diagnostic Hematology Center, Department of Hematology	Cherkasy
Ukraine	City Clinical Hospital No.4 of Dnipro City Council, City hematology center	Dnipropetrovsk
Ukraine	BMT Kiev Center	Kiev
Ukraine	Kiev Cancer Institute	Kiev
Ukraine	Institute of Blood Pathology and Transfusion Medicine, Department of Hematology with Laboratory Group	Lviv
Ukraine	Vinnytsia M.I. Pyrohov Regional Clinical Hospital, Department of Hematology	Vinnytsia
Ukraine	O.F. Herbachevskyi Regional Clinical Hospital, Hematology Department with Intensive Therapy Wards	Zhytomyr
United Kingdom	Belfast Heatlh & Social Care Trust Belfast City Hospital	Belfast	Northern Ireland
United Kingdom	University Hospitals Birmingham NHS Foundation Trust Queen Elizabeth Hospital	Birmingham
United Kingdom	Cardiff & Vale University Health Board University Hospital of Wales	Cardiff	Wales
United Kingdom	NHS Tayside Ninewells Hospital	Dundee	Scotland
United Kingdom	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	Royal Liverpool & Broadgreen University Hospital NHS Trust Royal Liverpool University Hospital	Liverpool
United Kingdom	Imperial College Healthcare NHS Trust Hammersmith Hospital	London
United Kingdom	King's College Hospital NHS Foundation Trust	London
United Kingdom	London North West Healthcare NHS Trust Northwick Park Hospital	London
United Kingdom	University College London	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 States	McFarland Clinic	Ames	Iowa
United States	SCOR AnMed Health Cancer Center	Anderson	South Carolina
United States	Emory University	Atlanta	Georgia
United States	University of Maryland	Baltimore	Maryland
United States	Central Care Cancer Center	Bolivar	Missouri
United States	University of Cincinnati Health	Cincinnati	Ohio
United States	Baylor Sammons Cancer Center	Dallas	Texas
United States	University of Texas Southwestern	Dallas	Texas
United States	Commonwealth Hematology	Danville	Kentucky
United States	Kaiser Permanente Hawaii	Honolulu	Hawaii
United States	Southwest Cancer Center of Oklahoma	Lawton	Oklahoma
United States	Norton Cancer Institute	Louisville	Kentucky
United States	Mount Sinai	New York	New York
United States	The Valley Hospital Luckow Pavilion	Paramus	New Jersey
United States	Boca Raton Clinical Research (BRCR) Medical Center	Plantation	Florida
United States	Kaiser Permanente Northwest OR	Portland	Oregon
United States	The Cancer Institute at St. Francis Hospital	Roslyn	New York
United States	Stormont Vail Health Care (Cotton O'Neil Cancer Center )	Topeka	Kansas
United States	Prairie Lakes Healthcare	Watertown	South Dakota
United States	Novant-Forsyth Memorial Hospital	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Karyopharm Therapeutics Inc

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Bulgaria,  Canada,  Czechia,  France,  Germany,  Greece,  Hungary,  India,  Israel,  Italy,  Poland,  Romania,  Russian Federation,  Serbia,  Spain,  Ukraine,  United Kingdom, 

Outcome

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