Selinexor (Nexpovio®) (SVd) in Patients With Relapsed or Refractory Multiple Myeloma - SEATTLE- (SEATTLE)

A Non-interventional Study of Selinexor (Nexpovio®) in Combination With Bortezomib and Dexamethasone (SVd) in Patients With Relapsed or Refractory Multiple Myeloma (R/RMM)

The non-interventional study SEATTLE aims to answer open scientific questions regarding QoL and tolerability/safety and AE management of selinexor as well as effectiveness and dosing in clinical routine. Thus, SEATTLE will provide real-world evidence complementary to pivotal studies.

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Selinexor

Detailed Description

Multiple myeloma (MM) accounts for approximately 10% of hematological malignancies. Since MM patients are elderly and often comorbid patients, risk-adapted treatment strategies to further improve outcome in is crucial.Selinexor, a potent, oral, SINE (selective inhibitors of nuclear exports) binds reversibly to XPO. This leads to nuclear localization and functional activation of tumor suppressor proteins, which further leads to suppression of nuclear factor κB activity, and reduction in oncoprotein mRNA translation. All this induces apoptosis of tumor cells. Since treatment options for MM are various and the most important factor is to keep or improve quality of life (QoL) of the patients, there is an urge for real-world clinical data of MM patients treated with selinexor in clinical routine. The objective of this non-interventional study is to evaluate QoL and tolerability/safety and AE management as well as effectiveness and dosing in adult patients with relapsed or refractory MM, which receive selinexor in combination with bortezomib and dexamethasone in the 2nd or later therapy line in a real-world setting.

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Daniel Kummer, Dr.; Phone Number: +49761-152420; Email: seattle@iomedico.com

Study Locations

• Austria
  • Wien, Austria, 1090
    • Not yet recruiting
    • Medizinische Universität Wien, Universitätsklinik für Innere Medizin I
    • Contact: Maria Krauth, Assoc. Prof. PD Dr.; Phone Number: +43 1 40400 - 44100; Email: maria.krauth@meduniwien.ac.at
• Germany
  • Baden-Württemberg
    • Ravensburg, Baden-Württemberg, Germany, 88212
      • Recruiting
      • Gemeinschaftspraxis für Hämatologie und Onkologie GbR
      • Contact: Tobias Dechow, Prof. Dr.; Phone Number: +49 751 366197-0; Email: info@onkonet.eu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Adult patients (≥18 years old) with relapsed or refractory multiple myeloma and decision for treatment with selinexor in combination with bortezomib and dexamethasone (SVd) in ≥2nd therapy line

Description

Inclusion Criteria:

• Relapsed or refractory multiple myeloma
• Indication and decision for ≥2nd-line treatment with selinexor in combination with bortezomib and dexamethasone according to current selinexor SmPC as assessed by the treating physician
• Treatment decision before inclusion into this non-interventional study
• Willingness and ability to participate in the electronic patient-reported outcome (ePRO) module and answering of questionnaires
• Age ≥18 years
• Signed and dated informed consent form
• Inclusion before start of treatment (prospective inclusion)

Exclusion Criteria:

• Contraindications according to selinexor SmPC for patients with MM
• Participation in an interventional clinical trial

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
second line and later lines therapy; Patients enrolled for second line or later lines therapy with selinexor in combination with bortezomib and dexamethasone.	Drug: Selinexor; Selinexor/bortezomib/dexamethasone according to Nexpovio® SmPC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline of EORTC global health scale	Change from baseline quality of life (QoL) over time for the global health scale of the EORTC QLQ- C30 questionnaire.	Baseline, up to 28 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline of EORTC QLQ-C30 further scales	Change from baseline in further scales of the EORTC QLQ-C30 questionnaire	Baseline, up to 28 months
Change from baseline of EORTC QLQ-MY20 further scales	Change from baseline in further scales of the EORTC QLQ-MY20 questionnaire	Baseline, up to 30 days after selinexor treatment
Assessment of drug tolerability and safety	Frequency of specific (serious) adverse drug reactions ((S)ADRs) (nausea, weight loss, diarrhea, vomiting, fatigue)	Baseline, up to 28 months
Adverse events (AEs) and serious adverse events (SAEs) according to NCI CTCAE	Incidence of (serious) AEs ((S)AEs) as characterized by type, frequency, severity and seriousness.	Baseline, up to 30 days after end of selinexor treatment
Adverse drug reaction (ADR) and serious adverse drug reactions (SADR)	Incidence of (serious) adverse drug reactions ((S)ADRs) as characterized by type, frequency, severity and seriousness.	Baseline, up to 30 days after end of selinexor treatment
Adverse events of special interest (AESI)	Incidence of AEs of special interest defined as cataracts (new-onset cataracts and worsening of cataracts) and Acute cerebellar syndrome.	Baseline, up to 30 days after end of selinexor treatment
Changes in selinexor therapy	Frequency of treatment delays, no administrations (skips), discontinuation (withdrawn) of selinexor due to safety reasons	From date of selinexor treatment start, up to 28 months
Effectiveness in routine treatment: Best response	Frequencies of best response during selinexor therapy will be calculated using descriptive statistics.	Baseline, up to 28 months
Effectiveness in routine treatment: Overall response rate (ORR)	ORR of patients will be calculated. ORR is defined as the proportion of patients achieving a complete response, very good partial response or partial response as best overall response. Patients without response measurement are considered non-responders.	Baseline, up to 28 months
Effectiveness in routine treatment: Disease control rate (DCR)	DCR is defined as the proportion of patients achieving complete response, very good partial response, partial response, or stable disease as best response. Patients without response measurement are considered non-responders.	Baseline, up to 28 months
Effectiveness in routine treatment: Progression-free survival (PFS)	PFS is defined as the time interval measured from the day of first selinexor administration to first progression or death, whichever comes first.	Baseline, up to 28 months
6 months PFS rate	PFS rates will be analysed 6 months after treatment start of selinexor	Baseline, until 6 months after start of selinexor treatment
12 months PFS rate	PFS rates will be analysed 12 months after treatment start of selinexor	Baseline, until 12 months after start of selinexor treatment
Effectiveness in routine treatment: Overall survival (OS)	OS is defined as the time interval measured from the day of first selinexor administration to time of death from any cause.	Baseline, up to 28 months
6 months OS rate	OS rates will be analysed 6 and 12 months after treatment start of selinexor	Baseline, until 6 months after start of selinexor treatment
12 months OS rate	OS rates will be analysed 6 and 12 months after treatment start of selinexor	Baseline, until 12 months after start of selinexor treatment
Selinexor therapy: Dosing	Dose intensity during treatment (mg/m2 per week) will be analysed	Baseline, up to end of selinexor treatment
Selinexor therapy: Frequency	Frequency of starting dose of selinexor (100 mg, 80 mg, 60 mg, other) will be analysed	Cycle 1, day 1
Selinexor therapy: Dose reduction of starting dose	Reasons for reduced starting dose compared to SmPC will be analysed	Cycle 1, day 1
Selinexor therapy: Dose changes	Reasons for dose reductions and dose re-escalation during treatment compared to previous dose	From date of second selinexor application, up to 28 months
Previous therapies	Frequency of distinct previous therapies (systemic / radiation / transplantation)	Baseline
Daratumumab-based previous therapies	Frequency of patients with daratumumab-based previous therapies	Baseline
Treatment duration	Treatment duration of selinexor therapy	From date of selinexor treatment start, up to 28 months
Subsequent antineoplastic therapies	Frequency of distinct subsequent antineoplastic therapies.	From Date of end of selinexor treatment up to 28 months
Subsequent antineoplastic transplantations	Frequency of distinct subsequent antineoplastic transplantations.	From Date of end of selinexor treatment up to 28 months
Subsequent antineoplastic radiations	Frequency of distinct subsequent antineoplastic radiations.	From Date of end of selinexor treatment up to 28 months
Frequency of concomitant medication	Frequency of concomitant medication administered	Baseline up to 30 days after end of selinexor therapy
Anti-emetic substances for AE treatment	Use of anti-emetic substances for AE treatment	Baseline up to 30 days after end of selinexor treatment
Anti-emetic substances for prophylaxis	Use of anti-emetic substances for prophlaxis	From date of selinexor treatment start, up to 28 months
Anti-diarrhea substances for AE treatment	Use of anti-diarrhea substances for AE treatment	Baseline up to 30 days after end of selinexor treatment
Anti-diarrhea substances for prophylaxis	Use of anti-diarrhea substances for prophylaxis	From date of selinexor treatment start, up to 28 months
Anti-emetic and anti-diarrhea substances for AE treatment	Use of anti-emetic and anti-diarrhea substances for AE treatment	From date of selinexor treatment start, up to date of end of selinexor treatment
Anti-emetic and anti-diarrhea substances for prophylaxis	Use of anti-emetic and anti-diarrhea substances for prophylaxis	From date of selinexor treatment start, up to date of end of selinexor treatment
Administration of Glucocorticoids and NK1 antagonist for prophylaxis	Frequency of glucocorticoids (i.e., dexamethasone given in addition to study medication) + NK1 antagonist administration used for prophylaxis.	From date of selinexor treatment start, up to 28 months
Administration of NK1 + 5HT3 antagonist for prophylaxis	Frequency of NK1 + 5HT3 antagonist administration used for prophylaxis	From date of selinexor treatment start, up to 28 months
Administration of Glucocorticoids and 5HT3 antagonist for prophylaxis	Frequency of glucocorticoids (i.e., dexamethasone given in addition to study medication) + 5HT3 antagonist administration used for prophylaxis.	From date of selinexor treatment start, up to 28 months
Administration of Glucocorticoids, NK1 and 5HT3 antagonist for prophylaxis	Frequency of glucocorticoids (i.e., dexamethasone given in addition to study medication) + NK1 + 5HT3 antagonist administration used for prophylaxis.	From date of selinexor treatment start, up to 28 months
Therapy decision	Assessment of parameters of therapy decision making.	Baseline
Therapy choice	Frequency of distinct parameters affecting therapy choice.	Baseline
Assessment of myeloma comorbidity index R-MCI	Assessment of R-MCI in all patients and patients with different starting doses	Baseline
R-MCI risk groups	Frequency of R-MCI risk groups in all patients and according to different selinexor starting dosages (100 mg vs. 80 mg vs. 60 mg).	Baseline

Collaborators and Investigators

• Sponsor: iOMEDICO AG
• Collaborators: Stemline Switzerland GmbH; Climedo Health GmbH
• Investigators: Study Chair: Tobias Dechow, Prof. Dr., Gemeinschaftspraxis für Hämatologie und Onkologie GbR; Study Chair: Maria Krauth, Assoc. Prof. PD Dr., Universitätsklinikum AKH Wien

Study record dates

Study Major Dates

• Study Start (Actual): June 28, 2023
• Primary Completion (Estimated): September 15, 2025
• Study Completion (Estimated): September 15, 2025

Study Registration Dates

• First Submitted: June 23, 2023
• First Submitted That Met QC Criteria: July 13, 2023
• First Posted (Actual): July 20, 2023

Study Record Updates

• Last Update Posted (Actual): July 20, 2023
• Last Update Submitted That Met QC Criteria: July 13, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Multiple Myeloma; Dexamethasone; Bortezomib; Selinexor
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: IOM-090494

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No