selinexor for Relapsed or refractory multiple myeloma

Inclusion criteria

• {"criterion_text":"- Relapsed or refractory MM per IMWG criteria (Appendix 2) with measurable disease as defined by at least 1 of the following: a. Serum M-protein ≥0.5 g/dL (≥5 g/L) by serum protein electrophoresis (SPEP) or, for immunoglobulin (Ig) A or D myeloma, by quantitative serum IgA or IgD levels ≥0.5 g/dL. b. Urinary M-protein excretion ≥200 mg/24 hours. c. Serum free light chain (FLC) ≥100 mg/L, provided that the FLC ratio is abnormal (normal FLC ratio: 0.26 to 1.65)."}
• {"criterion_text":"- Patients with active hepatitis B virus (HBV) are eligible if antiviral therapy for hepatitis B has been given for >8 weeks and viral load is <100 IU/mL. Patients with evidence of non-active HBV should be discussed with the Medical Monitor and should be monitored or receive prophylaxis at the discretion of the Investigator and study site institutional guidelines"}
• {"criterion_text":"- Patients with a history of hepatitis C virus (HCV) are eligible if they have received adequate curative anti-HCV treatment and HCV viral load is below the limit of quantification."}
• {"criterion_text":"- Patients with a history of human immunodeficiency virus (HIV) are eligible if they have CD4+ T cell counts ≥350 cells/μL, negative viral load, and no history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections in the last year and should be on established antiretroviral therapy (ART) for at least 4 weeks."}
• {"criterion_text":"- Global (excluding Germany): Female patients of childbearing potential must have a negative serum pregnancy test within 10 to 14 days and a second negative serum test within 24 hours prior to the first dose of study treatment. Female patients of childbearing potential who are sexually active must agree to use a barrier method in addition to highly effective methods of contraception throughout the study and for 90 days following the last dose of study treatment. Germany only: Premenopausal female patients of childbearing potential must have a negative serum pregnancy test within 10 to 14 days and a second negative serum test within 24 hours prior to the first dose of study treatment. Premenopausal female patients of childbearing potential who are sexually active must agree to use a barrier method in addition highly effective methods of contraception throughout the study and for 90 days following the last dose of study treatment."}
• {"criterion_text":"- Male patients who are sexually active must agree to use a barrier method in addition to highly effective methods of contraception throughout the study treatment period and for 90 days following the last dose of selinexor treatment. Male patients must agree not to donate sperm during the study treatment period and for at least 90 days after the last dose of selinexor treatment."}
• {"criterion_text":"- Age ≥18 years at the time of signing informed consent."}
• {"criterion_text":"- Written informed consent signed in accordance with federal, local, and institutional guidelines."}
• {"criterion_text":"- Patients must be able and willing to take enteric-coated aspirin according to clinical practice, or if history of prior thrombotic disease, must be fully anticoagulated with warfarin (international normalized ratio [INR] 2-3) or be treated with full -dose, low molecular weight heparin, as if to treat deep venous thrombosis (DVT)/pulmonary embolism (PE) at the Investigator's discretion. For patients on warfarin, INR should be repeated as clinically indicated. Use of alternative anticoagulants, such as direct oral anticoagulants, may be considered per Investigator discretion."}
• {"criterion_text":"- Received at least 1 and no more than 4 prior anti-MM lines of therapy. Induction therapy followed by stem cell transplant and consolidation/maintenance therapy will be considered as 1 line of therapy."}
• {"criterion_text":"- Prior therapy that includes ≥2 consecutive cycles of lenalidomide and a proteasome inhibitor given alone or in combination."}
• {"criterion_text":"- Prior therapy with an anti-CD38 mAb as part of their immediate last line of therapy prior to study entry. (Before protocol version 2.0, patients with any prior therapy with an anti-CD38 mAb were eligible for the study.)"}
• {"criterion_text":"- Eastern Cooperative Oncology Group (ECOG) performance status of ≤2."}
• {"criterion_text":"- Resolution of any clinically significant non-hematological toxicities (if any) from previous treatments to Grade ≤1 by Cycle 1 Day 1 (C1D1). Patients with clinically significant Grade 2 neuropathy from previous treatments may be included."}
• {"criterion_text":"- Adequate hepatic function within 28 days prior to C1D1: a. Total bilirubin <2 × upper limit of normal (ULN) (except patients with Gilbert's syndrome who must have a total bilirubin of <3 × ULN). b. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <2.5 × ULN."}
• {"criterion_text":"- Adequate renal function within 28 days prior to C1D1 (estimated creatinine clearance [CrCl] of ≥15 mL/min (not requiring dialysis), calculated using the formula of Cockcroft and Gault or measured by 24-hour urine collection)."}
• {"criterion_text":"- Adequate hematopoietic function within 7 days prior to C1D1 defined as absolute neutrophil count ≥1.5 x 10^9/L, hemoglobin ≥8.5 g/dL, and platelet count ≥100 x 10^9/L (patients for whom <50% of bone marrow nucleated cells are plasma cells) or ≥75 x 10^9/L (patients for whom ≥50% of bone marrow nucleated cells are plasma cells). a. Patients receiving hematopoietic growth factor support, including erythropoietin, darbepoetin, granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), and platelet stimulators (e.g., romiplostim, or eltrombopag) must have a 2-week interval between growth factor support and the Screening assessments. b. Patients must have: − At least a 2-week interval from the last red blood cell (RBC) transfusion prior to the Screening hemoglobin assessment, and − At least a 1-week interval from the last platelet transfusion prior to the Screening platelet assessment. However, patients may receive RBC and/or platelet transfusions as clinically indicated per institutional guidelines during the study."}

Exclusion criteria

• {"criterion_text":"- Smoldering MM"}
• {"criterion_text":"- Prior autologous stem cell transplantation <100 days or allogeneic stem cell transplantation <4 months prior to C1D1."}
• {"criterion_text":"- Major surgery within 4 weeks prior to C1D1."}
• {"criterion_text":"- Active graft versus host disease after allogeneic stem cell transplantation."}
• {"criterion_text":"- Pregnant or breastfeeding females."}
• {"criterion_text":"- In the opinion of the Investigator, patients who are below their ideal body weight and would be unduly impacted by changes in their weight."}
• {"criterion_text":"- Clinically significant cardiac disease, including: a. Myocardial infarction within 6 months before C1D1, or unstable or uncontrolled disease/condition related to or affecting cardiac function (e.g., unstable angina, congestive heart failure, New York Heart Association Class III-IV). b. Uncontrolled cardiac arrhythmia (CTCAE v5.0 Grade 2 or higher) or clinically significant electrocardiogram (ECG) abnormalities. c. Screening 12-lead ECG showing a baseline QT interval as corrected by Fridericia’s formula (QTcF [Appendix 4]) >470 msec."}
• {"criterion_text":"- Any active gastrointestinal dysfunction interfering with the patient’s ability to swallow tablets, or any active gastrointestinal dysfunction that could interfere with absorption of study treatment."}
• {"criterion_text":"- Any active, serious psychiatric, medical, or other conditions/situations that, in the opinion of the Investigator, could interfere with treatment, compliance, or the ability to give informed consent."}
• {"criterion_text":"- Contraindication to or inability to tolerate any of the required concomitant drugs, such as dual antiemetics (Section 10.1.1 ), or supportive treatments."}
• {"criterion_text":"- Patients unwilling or unable to comply with the protocol."}
• {"criterion_text":"- Plasma cell leukemia."}
• {"criterion_text":"- Documented active systemic amyloid light chain amyloidosis"}
• {"criterion_text":"- Any known history of central nervous system MM."}
• {"criterion_text":"- Prior treatment with: a. a selective inhibitor of nuclear export (SINE) compound, including selinexor. b. pomalidomide or elotuzumab."}
• {"criterion_text":"- Any concurrent medical condition or disease that is likely to interfere with study procedures."}
• {"criterion_text":"- Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within 1 week prior to C1D1. Patients on prophylactic antibiotics or with a controlled infection within 1 week prior to C1D1 are acceptable."}
• {"criterion_text":"- Known intolerance, hypersensitivity, or contraindication to any of the study treatments."}
• {"criterion_text":"- Radiation, chemotherapy, or immunotherapy or any other anticancer therapy including investigational therapies and high dose dexamethasone (i.e., 40 mg daily for 4 days per week) ≤2 weeks prior to C1D1. Patients on longterm glucocorticoids during Screening do not require a washout period but must be able to tolerate the specified dexamethasone dose in this study."}

Primary endpoints

• {"endpoint_text":"- PFS, defined as time from date of randomization until the date of first confirmed progressive disease (PD), per IMWG response criteria, or death due to any cause, whichever occurs first","definition_or_measurement_approach":"Time from date of randomization to first confirmed progressive disease per IMWG response criteria or death from any cause."}

Secondary endpoints

• {"endpoint_text":"- ORR, defined as any response ≥PR","definition_or_measurement_approach":"Overall response rate defined as any response equal to or greater than partial response (PR)."}
• {"endpoint_text":"- Overall survival (OS)","definition_or_measurement_approach":"Time from randomization to death from any cause (OS)."}
• {"endpoint_text":"- Clinical benefit rate (CBR), defined as response ≥minimal response (MR)","definition_or_measurement_approach":"CBR defined as any response equal to or greater than minimal response (MR)."}
• {"endpoint_text":"- Duration of response (DOR)","definition_or_measurement_approach":"Duration from first documented response until progression or death."}
• {"endpoint_text":"- Time to next treatment (TNT)","definition_or_measurement_approach":"Time from randomization to initiation of next anti-myeloma therapy."}
• {"endpoint_text":"- Time to initial response (TTR)","definition_or_measurement_approach":"Time from randomization to first documented response."}
• {"endpoint_text":"- Time to best response (TTBR)","definition_or_measurement_approach":"Time from randomization to best documented response."}
• {"endpoint_text":"- Time to progression after first post-SPd/EloPd treatment or death (PFS2)","definition_or_measurement_approach":"Time to disease progression or death following first subsequent anticancer therapy after study treatment (PFS2)."}

Other endpoints

• {"endpoint_text":"- Safety and tolerability of study treatment will be evaluated based on AE reports, vital signs, clinical laboratory results, electrocardiogram (ECG) and physical examination findings, by means of the occurrence, nature, and severity of AEs as categorized by the CTCAE v5.0","definition_or_measurement_approach":"Safety assessed by adverse event reports, vital signs, labs, ECG and physical examinations; AEs categorized per CTCAE v5.0."}
• {"endpoint_text":"- Patient-reported quality of life (QoL, as measured by the European Organisation for Research and Treatment of Cancer-Quality of Life (EORTC-QLQ-C30), EORTC-QLQ-MY20, and EQ-5D-5L instruments","definition_or_measurement_approach":"QoL measured using EORTC-QLQ-C30, EORTC-QLQ-MY20 and EQ-5D-5L questionnaires as patient-reported outcomes."}
• {"endpoint_text":"- Selinexor and pomalidomide PK parameters, estimations of maximum plasma concentration, area under the concentration versus time curve (AUC), and apparent clearance, if feasible.","definition_or_measurement_approach":"Pharmacokinetic parameters to include Cmax, AUC and apparent clearance estimates for selinexor and pomalidomide when feasible."}

France

Earliest CTIS Part Ii Submission Date

20-09-2024

Latest Decision Or Authorization Date

03-02-2026

Processing Time Days

501

Number Of Sites

4

Number Of Participants

32

Germany

Earliest CTIS Part Ii Submission Date

20-09-2024

Latest Decision Or Authorization Date

30-01-2026

Processing Time Days

497

Number Of Sites

4

Number Of Participants

11

Spain

Earliest CTIS Part Ii Submission Date

20-09-2024

Latest Decision Or Authorization Date

09-02-2026

Processing Time Days

507

Number Of Sites

14

Number Of Participants

10

Greece

Earliest CTIS Part Ii Submission Date

20-09-2024

Latest Decision Or Authorization Date

30-01-2026

Processing Time Days

497

Number Of Sites

4

Number Of Participants

25

Netherlands

Earliest CTIS Part Ii Submission Date

20-09-2024

Latest Decision Or Authorization Date

02-02-2026

Processing Time Days

500

Number Of Sites

2

Number Of Participants

11

Italy

Earliest CTIS Part Ii Submission Date

20-09-2024

Latest Decision Or Authorization Date

23-04-2026

Processing Time Days

580

Number Of Sites

23

Number Of Participants

27

Primary sponsor

Full Name

European Myeloma Network B.V.

Organisation Type

Patient organisation/association

Country Of Registered Address

Netherlands

Contract research organisations

Name

Next CRO SYMVOULOI FARMAKEUTIKON EPICHEIRISEON M.E.P.E.

Responsibilities

Sponsor duties codes: ["1","12","8"]

Name

C 2 R

Responsibilities

Sponsor duties codes: [{"code":"15","value":"Patient travel reimbursment"}]

Name

Precision for Medicine (HU) Kft.

Responsibilities

Sponsor duties codes: ["1","12","3","5","6","7","8","9"]

Third parties

• {"country":"France","full_name":"C 2 R","duties_or_roles":"Sponsor duties codes: [{\"code\":\"15\",\"value\":\"Patient travel reimbursment\"}]","organisation_type":"Pharmaceutical company"}
• {"country":"Greece","full_name":"Next CRO SYMVOULOI FARMAKEUTIKON EPICHEIRISEON M.E.P.E.","duties_or_roles":"Sponsor duties codes: [\"1\",\"12\",\"8\"]","organisation_type":"Pharmaceutical company"}
• {"country":"Netherlands","full_name":"Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)","duties_or_roles":"Sponsor duties codes: [\"4\"]","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Greece","full_name":"Bioiatriki Private Medical Polyclinic S.A.","duties_or_roles":"Sponsor duties codes: [\"4\"]","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Q Squared Solutions LLC","duties_or_roles":"Sponsor duties codes: [{\"code\":\"15\",\"value\":\"Pharmacokinetics\"}]","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom","full_name":"Medidata Solutions International Limited","duties_or_roles":"Sponsor duties codes: [\"3\"]","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"Cerba Research","duties_or_roles":"Sponsor duties codes: [\"4\"]","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Germany","full_name":"University Medical Center Hamburg-Eppendorf","duties_or_roles":"Sponsor duties codes: [\"4\"]","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Hungary","full_name":"Precision for Medicine (HU) Kft.","duties_or_roles":"Sponsor duties codes: [\"1\",\"12\",\"3\",\"5\",\"6\",\"7\",\"8\",\"9\"]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Transperfect Translations International Inc.","duties_or_roles":"Sponsor duties codes: [{\"code\":\"15\",\"value\":\"Translation Services\"}]","organisation_type":"Pharmaceutical company"}
• {"country":"Italy","full_name":"Emn Trial Office S.r.l. Impresa Sociale","duties_or_roles":"Sponsor duties codes: [\"4\"]","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"France","full_name":"Histalim","duties_or_roles":"Sponsor duties codes: [\"4\"]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"Sponsor duties codes: [\"6\",\"7\"]","organisation_type":"Non-Pharmaceutical company"}