Multiple Myeloma
Conditions
Keywords
Multiple Myeloma, Selinexor, Bortezomib, Dexamethasone
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.
Interventions
DRUGSelinexor
Selinexor/bortezomib/dexamethasone according to Nexpovio® SmPC
Sponsors
Menarini Stemline
Climedo Health GmbH
iOMEDICO AG
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline of EORTC global health scale | Baseline, up to 40 months | Change from baseline quality of life (QoL) over time for the global health scale of the EORTC QLQ- C30 questionnaire. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline of EORTC QLQ-MY20 further scales | Baseline, up to 30 days after selinexor treatment | Change from baseline in further scales of the EORTC QLQ-MY20 questionnaire |
| Assessment of drug tolerability and safety | Baseline, up to 40 months | Frequency of specific (serious) adverse drug reactions ((S)ADRs) (nausea, weight loss, diarrhea, vomiting, fatigue) |
| Adverse events (AEs) and serious adverse events (SAEs) according to NCI CTCAE | Baseline, up to 30 days after end of selinexor treatment | Incidence of (serious) AEs ((S)AEs) as characterized by type, frequency, severity and seriousness. |
| Adverse drug reaction (ADR) and serious adverse drug reactions (SADR) | Baseline, up to 30 days after end of selinexor treatment | Incidence of (serious) adverse drug reactions ((S)ADRs) as characterized by type, frequency, severity and seriousness. |
| Adverse events of special interest (AESI) | Baseline, up to 30 days after end of selinexor treatment | Incidence of AEs of special interest defined as cataracts (new-onset cataracts and worsening of cataracts) and Acute cerebellar syndrome. |
| Changes in selinexor therapy | From date of selinexor treatment start, up to 40 months | Frequency of treatment delays, no administrations (skips), discontinuation (withdrawn) of selinexor due to safety reasons |
| Effectiveness in routine treatment: Best response | Baseline, up to 40 months | Frequencies of best response during selinexor therapy will be calculated using descriptive statistics. |
| Effectiveness in routine treatment: Overall response rate (ORR) | Baseline, up to 40 months | 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. |
| Effectiveness in routine treatment: Disease control rate (DCR) | Baseline, up to 40 months | 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. |
| Effectiveness in routine treatment: Progression-free survival (PFS) | Baseline, up to 40 months | PFS is defined as the time interval measured from the day of first selinexor administration to first progression or death, whichever comes first. |
| 6 months PFS rate | Baseline, until 6 months after start of selinexor treatment | PFS rates will be analysed 6 months after treatment start of selinexor |
| 12 months PFS rate | Baseline, until 12 months after start of selinexor treatment | PFS rates will be analysed 12 months after treatment start of selinexor |
| Effectiveness in routine treatment: Overall survival (OS) | Baseline, up to 40 months | OS is defined as the time interval measured from the day of first selinexor administration to time of death from any cause. |
| 6 months OS rate | Baseline, until 6 months after start of selinexor treatment | OS rates will be analysed 6 and 12 months after treatment start of selinexor |
| 12 months OS rate | Baseline, until 12 months after start of selinexor treatment | OS rates will be analysed 6 and 12 months after treatment start of selinexor |
| Selinexor therapy: Dosing | Baseline, up to end of selinexor treatment | Dose intensity during treatment (mg/m2 per week) will be analysed |
| Selinexor therapy: Frequency | Cycle 1, day 1 | Frequency of starting dose of selinexor (100 mg, 80 mg, 60 mg, other) will be analysed |
| Selinexor therapy: Dose reduction of starting dose | Cycle 1, day 1 | Reasons for reduced starting dose compared to SmPC will be analysed |
| Selinexor therapy: Dose changes | From date of second selinexor application, up to 40 months | Reasons for dose reductions and dose re-escalation during treatment compared to previous dose |
| Previous therapies | Baseline | Frequency of distinct previous therapies (systemic / radiation / transplantation) |
| Daratumumab-based previous therapies | Baseline | Frequency of patients with daratumumab-based previous therapies |
| Treatment duration | From date of selinexor treatment start, up to 40 months | Treatment duration of selinexor therapy |
| Subsequent antineoplastic therapies | From Date of end of selinexor treatment up to 40 months | Frequency of distinct subsequent antineoplastic therapies. |
| Subsequent antineoplastic transplantations | From Date of end of selinexor treatment up to 40 months | Frequency of distinct subsequent antineoplastic transplantations. |
| Subsequent antineoplastic radiations | From Date of end of selinexor treatment up to 40 months | Frequency of distinct subsequent antineoplastic radiations. |
| Frequency of concomitant medication | Baseline up to 30 days after end of selinexor therapy | Frequency of concomitant medication administered |
| Anti-emetic substances for AE treatment | Baseline up to 30 days after end of selinexor treatment | Use of anti-emetic substances for AE treatment |
| Anti-emetic substances for prophylaxis | From date of selinexor treatment start, up to 40 months | Use of anti-emetic substances for prophlaxis |
| Anti-diarrhea substances for AE treatment | Baseline up to 30 days after end of selinexor treatment | Use of anti-diarrhea substances for AE treatment |
| Anti-diarrhea substances for prophylaxis | From date of selinexor treatment start, up to 40 months | Use of anti-diarrhea substances for prophylaxis |
| Anti-emetic and anti-diarrhea substances for AE treatment | From date of selinexor treatment start, up to date of end of selinexor treatment | Use of anti-emetic and anti-diarrhea substances for AE treatment |
| Anti-emetic and anti-diarrhea substances for prophylaxis | From date of selinexor treatment start, up to date of end of selinexor treatment | Use of anti-emetic and anti-diarrhea substances for prophylaxis |
| Administration of Glucocorticoids and NK1 antagonist for prophylaxis | From date of selinexor treatment start, up to 40 months | Frequency of glucocorticoids (i.e., dexamethasone given in addition to study medication) + NK1 antagonist administration used for prophylaxis. |
| Administration of NK1 + 5HT3 antagonist for prophylaxis | From date of selinexor treatment start, up to 40 months | Frequency of NK1 + 5HT3 antagonist administration used for prophylaxis |
| Administration of Glucocorticoids and 5HT3 antagonist for prophylaxis | From date of selinexor treatment start, up to 40 months | Frequency of glucocorticoids (i.e., dexamethasone given in addition to study medication) + 5HT3 antagonist administration used for prophylaxis. |
| Change from baseline of EORTC QLQ-C30 further scales | Baseline, up to 40 months | Change from baseline in further scales of the EORTC QLQ-C30 questionnaire |
| Therapy decision | Baseline | Assessment of parameters of therapy decision making. |
| Therapy choice | Baseline | Frequency of distinct parameters affecting therapy choice. |
| Assessment of myeloma comorbidity index R-MCI | Baseline | Assessment of R-MCI in all patients and patients with different starting doses |
| R-MCI risk groups | Baseline | Frequency of R-MCI risk groups in all patients and according to different selinexor starting dosages (100 mg vs. 80 mg vs. 60 mg). |
| Administration of Glucocorticoids, NK1 and 5HT3 antagonist for prophylaxis | From date of selinexor treatment start, up to 40 months | Frequency of glucocorticoids (i.e., dexamethasone given in addition to study medication) + NK1 + 5HT3 antagonist administration used for prophylaxis. |
Countries
Austria, Germany
Outcome results
None listed