Selinexor, Dexamethasone and Bortezomib in Patients with Multiple Myeloma

Phase 1

• Conditions: Penta-refractory multiple myeloma and triple-class refractory multiple myeloma; MedDRA version: 21.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2020-000821-22-GR
• Lead Sponsor: Karyopharm Therapeutics Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-05-07
• Last Update Posted: 11 May 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 134

Inclusion Criteria

1. Age =18 years at the time of signing informed consent.
2. Written informed consent in accordance with federal, local, and institutional guidelines.
3. 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.
4. Only for arms Sd-40 BIW, Sd-100 QW and Sd-80 BIW: Patients must have relapsed or refractory multiple myeloma (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 immunomodulatory agent (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.
5. 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.
6. Eastern Cooperative Oncology Group (ECOG) performance status of =2.
7. 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.
8. Patient agrees to provide bone marrow aspirate to be used for genetic testing of DNA and RNA.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 54
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 80

Exclusion Criteria

1. Active plasma cell leukemia.
2. Documented systemic amyloid light chain amyloidosis.
3. Active central nervous system multiple myeloma (MM).
4. Only for SVd arm: 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.
5. 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).
6. Active graft vs. host disease (after allogeneic stem cell transplantation) at C1D1.
7. Ongoing clinically significant non-hematological toxicities from prior treatments that are
Grade >2 at C1D1.
8. 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.
9. Inadequate renal function defined as estimated creatinine clearance of <20 mL/min, calculated using the formula of Cockroft and Gault.
10. Inadequate hematopoietic function defined as the following:
a. Absolute neutrophil count (ANC) <1000/mm3.
b. Platelet count <75,000/mm3
c. Hemoglobin (Hb) level <8.5 g/dL
11. Life expectancy of <4 months, based on the opinion of the Investigator.
12. Major surgery within 4 weeks prior to C1D1.
13. Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within 1 week prior to first dose.
14. Active gastrointestinal dysfunction interfering with the ability to swallow tablets, or any gastrointestinal dysfunction that could interfere with absorption of the study treatment.
15. Known active hepatitis A, B, or C infection; or known to be positive for hepatitis C virus RNA or hepatitis B virus surface antigen.
16. Receipt of red blood cells (RBC) transfusions within 2 weeks of C1D1.
17. Receipt of platelet transfusion within 1 week of C1D1.
18. Receipt of the following blood growth factors within 2 weeks prior to C1D1: Granulocyte colony stimulating factor, granulocyte-macrophage colony stimulating factor, erythropoietin, or megakaryocyte growth factor.
19. Female patients who are pregnant or lactating.
20. Known intolerance to or contraindication for glucocorticoid therapy at C1D1.
21. Concurrent therapy with approved or investigational anticancer therapeutic including topical therapies.
22. Prior exposure to a SINE compound, including selinexor.
23. Serious, active psychiatric or medical conditions which, in the opinion of the Investigator or Sponsor, could interfere with the participation in the study.
24. Contraindication to any of the required concomitant drugs or supportive treatments.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified