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

Study Overview
=================
Brief Summary
-----------------
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.

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.

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

Conditions
-----------------
Multiple Myeloma

Intervention / Treatment
-----------------
* Drug: Selinexor


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| second line and later lines therapy<br>Patients enrolled for second line or later lines therapy with selinexor in combination with bortezomib and dexamethasone. | Drug: Selinexor<br>* Selinexor/bortezomib/dexamethasone according to Nexpovio® SmPC<br>|

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Multiple Myeloma, Selinexor, Bortezomib, Dexamethasone