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

Recruiting
Conditions
Multiple Myeloma
Interventions
Registration Number
NCT05954780
Lead Sponsor
iOMEDICO AG
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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
100
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 & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
second line and later lines therapySelinexorPatients enrolled for second line or later lines therapy with selinexor in combination with bortezomib and dexamethasone.
Primary Outcome Measures
NameTimeMethod
Change from baseline of EORTC global health scaleBaseline, 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 Outcome Measures
NameTimeMethod
Therapy choiceBaseline

Frequency of distinct parameters affecting therapy choice.

Selinexor therapy: DosingBaseline, up to end of selinexor treatment

Dose intensity during treatment (mg/m2 per week) will be analysed

Effectiveness in routine treatment: Best responseBaseline, up to 40 months

Frequencies of best response during selinexor therapy will be calculated using descriptive statistics.

Daratumumab-based previous therapiesBaseline

Frequency of patients with daratumumab-based previous therapies

Treatment durationFrom date of selinexor treatment start, up to 40 months

Treatment duration of selinexor therapy

Selinexor therapy: FrequencyCycle 1, day 1

Frequency of starting dose of selinexor (100 mg, 80 mg, 60 mg, other) will be analysed

Change from baseline of EORTC QLQ-MY20 further scalesBaseline, up to 30 days after selinexor treatment

Change from baseline in further scales of the EORTC QLQ-MY20 questionnaire

12 months PFS rateBaseline, until 12 months after start of selinexor treatment

PFS rates will be analysed 12 months after treatment start of selinexor

6 months PFS rateBaseline, until 6 months after start of selinexor treatment

PFS rates will be analysed 6 months after treatment start of selinexor

Selinexor therapy: Dose reduction of starting doseCycle 1, day 1

Reasons for reduced starting dose compared to SmPC will be analysed

Frequency of concomitant medicationBaseline up to 30 days after end of selinexor therapy

Frequency of concomitant medication administered

Anti-emetic substances for prophylaxisFrom date of selinexor treatment start, up to 40 months

Use of anti-emetic substances for prophlaxis

Administration of Glucocorticoids and NK1 antagonist for prophylaxisFrom 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 Glucocorticoids and 5HT3 antagonist for prophylaxisFrom 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 scalesBaseline, up to 40 months

Change from baseline in further scales of the EORTC QLQ-C30 questionnaire

Assessment of drug tolerability and safetyBaseline, up to 40 months

Frequency of specific (serious) adverse drug reactions ((S)ADRs) (nausea, weight loss, diarrhea, vomiting, fatigue)

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 therapyFrom 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: 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.

Adverse events (AEs) and serious adverse events (SAEs) according to NCI CTCAEBaseline, 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.

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.

6 months OS rateBaseline, 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 rateBaseline, until 12 months after start of selinexor treatment

OS rates will be analysed 6 and 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.

Previous therapiesBaseline

Frequency of distinct previous therapies (systemic / radiation / transplantation)

Subsequent antineoplastic therapiesFrom Date of end of selinexor treatment up to 40 months

Frequency of distinct subsequent antineoplastic therapies.

Anti-diarrhea substances for AE treatmentBaseline up to 30 days after end of selinexor treatment

Use of anti-diarrhea substances for AE treatment

Assessment of myeloma comorbidity index R-MCIBaseline

Assessment of R-MCI in all patients and patients with different starting doses

R-MCI risk groupsBaseline

Frequency of R-MCI risk groups in all patients and according to different selinexor starting dosages (100 mg vs. 80 mg vs. 60 mg).

Selinexor therapy: Dose changesFrom date of second selinexor application, up to 40 months

Reasons for dose reductions and dose re-escalation during treatment compared to previous dose

Subsequent antineoplastic radiationsFrom Date of end of selinexor treatment up to 40 months

Frequency of distinct subsequent antineoplastic radiations.

Anti-emetic substances for AE treatmentBaseline up to 30 days after end of selinexor treatment

Use of anti-emetic substances for AE treatment

Anti-diarrhea substances for prophylaxisFrom date of selinexor treatment start, up to 40 months

Use of anti-diarrhea substances for prophylaxis

Anti-emetic and anti-diarrhea substances for AE treatmentFrom date of selinexor treatment start, up to date of end of selinexor treatment

Use of anti-emetic and anti-diarrhea substances for AE treatment

Administration of NK1 + 5HT3 antagonist for prophylaxisFrom date of selinexor treatment start, up to 40 months

Frequency of NK1 + 5HT3 antagonist administration used for prophylaxis

Therapy decisionBaseline

Assessment of parameters of therapy decision making.

Subsequent antineoplastic transplantationsFrom Date of end of selinexor treatment up to 40 months

Frequency of distinct subsequent antineoplastic transplantations.

Anti-emetic and anti-diarrhea substances for prophylaxisFrom 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, NK1 and 5HT3 antagonist for prophylaxisFrom 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.

Trial Locations

Locations (2)

Gemeinschaftspraxis für Hämatologie und Onkologie GbR

🇩🇪

Ravensburg, Baden-Württemberg, Germany

Medizinische Universität Wien, Universitätsklinik für Innere Medizin I

🇦🇹

Wien, Austria

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