SELINEXOR for Multiple myeloma|Penta-refractory multiple myeloma|Triple-class refractory multiple myeloma|Relapsed/refractory multiple myeloma

Inclusion criteria

• {"criterion_text":"- Age ≥18 years at the time of signing informed consent.\n- Written informed consent signed in accordance with federal, local, and institutional guidelines.\n- Measurable multiple myeloma (MM) based on International Myeloma Working Group (IMWG) guidelines as defined by at least one of the following: a. Serum M-protein ≥0.5 g/dL by serum protein electrophoresis (SPEP) or, for Immunoglobulin (Ig) A myeloma, by quantitative IgA. b. Urinary M-protein excretion ≥200 mg/24 hours. c. Free light chain (FLC) ≥100 mg/L, provided that the FLC ratio is abnormal.\n- Only for Arms Sd-40 BIW, Sd-100 QW and Sd-80 BIW prior to PV 5.0: Patients must have RRMM and have previously received at least 4 anti-MM prior therapies and have MM that is refractory to previous treatment with at least 2 PIs, at least 2 IMiDs, and 1 anti-CD38 monoclonal antibody. Refractory is defined as ≤25% response to therapy, or progression during therapy or progression within 60 days after completion of therapy. Only for Arms Sd-40 BIW and Sd-100 QW as of PV 5.0: Patients must have RR MM and have been previously treated with ≥3 anti-MM therapies (with exposure to at least 2 PI drugs, at least 2 IMiDs, and 1 anti-CD38 monoclonal antibody), and be refractory to at least 1 drug of each class (PI/IMiD/anti-CD38). Refractory is defined as ≤25% response to therapy or progression during therapy or progression within 60 days after completion of therapy.\n- Only for arm SVd: Patients must have previously received 1 to 5 anti- MM prior therapies and have MM that is refractory to previous treatment with at least 1 PI, at least 1 IMiD, and 1 anti-CD38 monoclonal antibody.\n- Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.\n- Female patients of childbearing potential must agree to use dual methods of contraception and have a negative serum pregnancy test at screening, and male patients must use an effective barrier method of contraception if sexually active with a female of childbearing potential. For both male and female patients, effective methods of contraception must be used throughout the study and for 7 months for female and 4 months for male following the discontinuation of study treatment."}

Exclusion criteria

• {"criterion_text":"- Active plasma cell leukemia.\n- Inadequate hematopoietic function defined as the following: a. Absolute neutrophil count (ANC) <1,000/mm3 b. Platelet count <75,000/mm3 c. Hemoglobin (Hb) level <8.0 g/dL\n- Life expectancy of <4 months, based on the opinion of the Investigator.\n- Major surgery within 4 weeks prior to C1D1.\n- Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within 1 week prior to first dose.\n- Active gastrointestinal dysfunction interfering with the ability to swallow tablets, or any gastrointestinal dysfunction that could interfere with absorption of the study treatment.\n- Known active hepatitis A, B, or C infection; or known to be positive for hepatitis C virus RNA or hepatitis B virus surface antigen.\n- Female patients who are pregnant or lactating.\n- Known intolerance, hypersensitivity, or contraindication to glucocorticoid therapy at C1D1.\n- Concurrent therapy with approved or investigational anticancer therapeutic including topical therapies.\n- Prior exposure to a SINE compound, including selinexor.\n- Documented systemic amyloid light chain amyloidosis.\n- Serious, active psychiatric or active medical conditions which, in the opinion of the Investigator or the Sponsor, could interfere with participation in the study.\n- Contraindication to any of the required concomitant drugs or supportive treatments.\n- Active central nervous system MM.\n- Only for Arm SVd: Greater than Grade 2 peripheral neuropathy or Grade ≥2 peripheral neuropathy with pain at baseline, regardless of whether or not the patient is currently receiving medication.\n- Radiation, chemotherapy, immunotherapy, or any other anticancer therapy (including investigational therapies) ≤2 weeks prior to Cycle 1 Day 1 (C1D1). (Steroids are permitted up to 1 pulse of 40 mg per day for 4 days in the 2 weeks prior to C1D1.)\n- Active graft vs. host disease (after allogeneic stem cell transplantation) at C1D1.\n- Ongoing clinically significant non-hematological toxicities from prior treatments that are Grade >2 at C1D1.\n- Inadequate hepatic function defined as total bilirubin ≥2x upper limit of normal (ULN) (≥3x ULN for patients with Gilbert’s syndrome), aspartate transaminase (AST) ≥2.5x ULN, and alanine transaminase (ALT) ≥2.5x ULN.\n- Inadequate renal function defined as estimated creatinine clearance of <20 mL/min, calculated using the formula of Cockroft and Gault (Section 9.5.4)."}

Primary endpoints

• {"endpoint_text":"- ORR defined as the proportion of patients who achieve stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) as assessed by the Investigator based on International Myeloma Working Group (IMWG) response criteria will be analyzed separately for each arm","definition_or_measurement_approach":"Assessed by the Investigator based on International Myeloma Working Group (IMWG) response criteria; proportion of patients achieving sCR, CR, VGPR, or PR; analyzed separately for each arm."}

Secondary endpoints

• {"endpoint_text":"- The following endpoints will be analyzed separately for each arm: • Duration of response (DOR) • Clinical benefit rate (CBR) • Disease control rate (DCR) • Progression-free survival (PFS) • Overall survival (OS) • Time to next treatment (TTNT)","definition_or_measurement_approach":"Each endpoint analyzed separately for each arm as stated."}
• {"endpoint_text":"- The safety and tolerability of study drug will be evaluated based on AE reports, vital signs, and clinical laboratory results by means of the occurrence, nature, and severity of AEs as categorized by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0","definition_or_measurement_approach":"Safety assessed by AE reports, vital signs, clinical laboratory results; AEs categorized by CTCAE v5.0."}

Greece

Earliest CTIS Part Ii Submission Date

04-09-2024

Latest Decision Or Authorization Date

23-09-2024

Processing Time Days

19

Number Of Sites

3

Number Of Participants

55

Primary sponsor

Full Name

Karyopharm Therapeutics Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

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

Responsibilities

sponsorDuties codes: 1; 12

Name

Icon Clinical Research Limited

Responsibilities

Site payments

Third parties

• {"country":"United States","full_name":"Labconnect LLC","duties_or_roles":"4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Greece","full_name":"Next CRO SYMVOULOI FARMAKEUTIKON EPICHEIRISEON M.E.P.E.","duties_or_roles":"1; 12","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"15 (Site payments)","organisation_type":"Pharmaceutical company"}
• {"country":"Hungary","full_name":"Precision for Medicine (HU) Kft.","duties_or_roles":"1; 12; 5","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"4g Clinical LLC","duties_or_roles":"3","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"15 (RAVE, Data transfer, CTMS; QOL/ePRO); 6","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Frontage Laboratories Inc.","duties_or_roles":"15 (Bortezomib PK bioanalysis)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Eclinical Solutions LLC","duties_or_roles":"6","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Universidad De Navarra","duties_or_roles":"15 (Genetic analysis-FISH/Karyotyping)","organisation_type":"Educational Institution"}