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.
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
75
Selinexor/bortezomib/dexamethasone according to Nexpovio® SmPC
Medizinische Universität Wien, Universitätsklinik für Innere Medizin I
Vienna, Austria
Gemeinschaftspraxis für Hämatologie und Onkologie GbR
Ravensburg, Baden-Wurttemberg, Germany
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.
Time frame: Baseline, up to 40 months
Change from baseline of EORTC QLQ-C30 further scales
Change from baseline in further scales of the EORTC QLQ-C30 questionnaire
Time frame: Baseline, up to 40 months
Change from baseline of EORTC QLQ-MY20 further scales
Change from baseline in further scales of the EORTC QLQ-MY20 questionnaire
Time frame: 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)
Time frame: Baseline, up to 40 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.
Time frame: 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.
Time frame: 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.
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Time frame: 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
Time frame: From date of selinexor treatment start, up to 40 months
Effectiveness in routine treatment: Best response
Frequencies of best response during selinexor therapy will be calculated using descriptive statistics.
Time frame: Baseline, up to 40 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.
Time frame: Baseline, up to 40 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.
Time frame: Baseline, up to 40 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.
Time frame: Baseline, up to 40 months
6 months PFS rate
PFS rates will be analysed 6 months after treatment start of selinexor
Time frame: 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
Time frame: 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.
Time frame: Baseline, up to 40 months
6 months OS rate
OS rates will be analysed 6 and 12 months after treatment start of selinexor
Time frame: 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
Time frame: Baseline, until 12 months after start of selinexor treatment
Selinexor therapy: Dosing
Dose intensity during treatment (mg/m2 per week) will be analysed
Time frame: 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
Time frame: Cycle 1, day 1
Selinexor therapy: Dose reduction of starting dose
Reasons for reduced starting dose compared to SmPC will be analysed
Time frame: Cycle 1, day 1
Selinexor therapy: Dose changes
Reasons for dose reductions and dose re-escalation during treatment compared to previous dose
Time frame: From date of second selinexor application, up to 40 months
Previous therapies
Frequency of distinct previous therapies (systemic / radiation / transplantation)
Time frame: Baseline
Daratumumab-based previous therapies
Frequency of patients with daratumumab-based previous therapies
Time frame: Baseline
Treatment duration
Treatment duration of selinexor therapy
Time frame: From date of selinexor treatment start, up to 40 months
Subsequent antineoplastic therapies
Frequency of distinct subsequent antineoplastic therapies.
Time frame: From Date of end of selinexor treatment up to 40 months
Subsequent antineoplastic transplantations
Frequency of distinct subsequent antineoplastic transplantations.
Time frame: From Date of end of selinexor treatment up to 40 months
Subsequent antineoplastic radiations
Frequency of distinct subsequent antineoplastic radiations.
Time frame: From Date of end of selinexor treatment up to 40 months
Frequency of concomitant medication
Frequency of concomitant medication administered
Time frame: Baseline up to 30 days after end of selinexor therapy
Anti-emetic substances for AE treatment
Use of anti-emetic substances for AE treatment
Time frame: Baseline up to 30 days after end of selinexor treatment
Anti-emetic substances for prophylaxis
Use of anti-emetic substances for prophlaxis
Time frame: From date of selinexor treatment start, up to 40 months
Anti-diarrhea substances for AE treatment
Use of anti-diarrhea substances for AE treatment
Time frame: Baseline up to 30 days after end of selinexor treatment
Anti-diarrhea substances for prophylaxis
Use of anti-diarrhea substances for prophylaxis
Time frame: From date of selinexor treatment start, up to 40 months
Anti-emetic and anti-diarrhea substances for AE treatment
Use of anti-emetic and anti-diarrhea substances for AE treatment
Time frame: 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
Time frame: 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.
Time frame: From date of selinexor treatment start, up to 40 months
Administration of NK1 + 5HT3 antagonist for prophylaxis
Frequency of NK1 + 5HT3 antagonist administration used for prophylaxis
Time frame: From date of selinexor treatment start, up to 40 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.
Time frame: From date of selinexor treatment start, up to 40 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.
Time frame: From date of selinexor treatment start, up to 40 months
Therapy decision
Assessment of parameters of therapy decision making.
Time frame: Baseline
Therapy choice
Frequency of distinct parameters affecting therapy choice.
Time frame: Baseline
Assessment of myeloma comorbidity index R-MCI
Assessment of R-MCI in all patients and patients with different starting doses
Time frame: 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).
Time frame: Baseline