A Study of Selinexor (KPT-330) Plus Low-Dose Dexamethasone in Previously Treated Patients with Multiple Myeloma
- Conditions
- Refractory multiple myeloma (RMM)MedDRA version: 20.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2016-003094-18-DE
- Lead Sponsor
- Karyopharm Therapeutics Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 210
1. Written informed consent in accordance with federal, local, and institutional guidelines.
2. Age = 18 years at the time of signing informed consent.
3. Measurable MM based on IMWG guidelines as defined by at least one of the following:
a. Serum M-protein = 0.5 g/dL by serum electrophoresis (SPEP) or, for IgA myeloma, by quantitative IgA b. Urinary M-protein excretion = 200 mg/24 hours
c. FLC = 100 mg/L, provided that the FLC ratio is abnormal.
d. If serum protein electrophoresis is felt to be unreliable for routine Mprotein measurement, then quantitative Ig levels by nephelometry is acceptable.
4. Patients must have previously received = 3 anti-MM regimens including: an alkylating agent, lenalidomide, pomalidomide, bortezomib, carfilzomib, daratumumab, and a glucocorticoid. There is no upper limit on the number of prior therapies provided that all other inclusion/exclusion criteria are met.
5. MM refractory to previous treatment with one or more glucocorticoids, parenteral PI (i.e., bortezomib and/or carfilzomib), IMiD (i.e., lenalidomide and/or pomalidomide), and daratumumab. Refractory is defined as = 25% response to therapy, or progression during therapy or progression within 60 days after completion of therapy.
6. Multiple myeloma that is refractory to the patient's most recent anti- MM regimen. (Documented severe intolerance to the patient's last therapy is allowed upon approval by the Medical Monitor.)
7. Any clinically significant non-hematological toxicities (except for peripheral neuropathy as described in exclusion criterion #17) that patients experienced from treatments in previous clinical studies must have resolved to Grade =2 by Cycle 1 Day 1.
8. Adequate hepatic function within 21 days prior to Cycle 1 Day 1: total bilirubin < 2x upper limit of normal (ULN) (except patients with Gilbert's syndrome who must have a total bilirubin of < 3x ULN), AST < 2.5x ULN and ALT < 2.5x ULN.
9. Adequate renal function within 21 days prior to Cycle 1 Day 1: estimated creatinine clearance of = 20 mL/min, calculated using the formula of Cockroft and Gault.
10. Female patients of childbearing potential must agree to use 2 methods of contraception (including 1 highly effective and 1 effective method of contraception) 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 three months following the last dose of study treatment.
11. Eastern Cooperative Oncology Group (ECOG) Performance Status of = 2.
12. Adequate hematopoietic function within 21 days prior to Cycle 1 Day 1 (See Exclusion Criterion #20 for transfusion washout periods for RBCs and platelets):
a. Total WBC count = 1,000/mm3
b. ANC = 1000/mm3
c. Platelet count = 75,000/mm3 (patients in whom <50% of bone marrow nucleated cells are plasma cells) or = 50,000/mm3 (patients in whom = 50% of bone marrow nucleated cells are plasma cells. [Platelet transfusions <1 week prior to Cycle 1 Day 1 are prohibited (see below).]
13. Hemoglobin level = 8.5 g/dL. In certain cases, patients with st
1. Active smoldering MM.
2. Active plasma cell leukemia.
3. Documented systemic amyloid light chain amyloidosis.
4. Active central nervous system (CNS) MM.
5. Pregnancy or breastfeeding.
6. Radiation, chemotherapy, or immunotherapy or any other anticancer therapy = 2 weeks prior to Cycle 1 Day 1, and radio-immunotherapy 6 weeks prior to Cycle 1 Day 1.
7. Active graft vs. host disease (after allogeneic stem cell transplantation) at Cycle 1 Day 1
8. Life expectancy of < 4 months.
9. Major surgery within four weeks prior to Cycle 1 Day 1.
10. Active, unstable cardiovascular function:
a. Symptomatic ischemia, or
b. Uncontrolled clinically-significant conduction abnormalities (e.g., patients with ventricular tachycardia on antiarrhythmics are excluded; patients with 1st degree atrioventricular (AV) block or asymptomatic left anterior fascicular block/right bundle branch block (LAFB/RBBB) will not be excluded), or
c. Congestive heart failure (CHF) of New York Heart Association (NYHA) Class = 3, or d. Myocardial infarction (MI) within 3 months prior to Cycle 1 Day 1.
11. Active, uncontrolled hypertension.
12. Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose.
13. Known HIV seropositive.
14. Known active hepatitis A, B, or C infection; or known to be positive for HCV RNA or HBsAg (HBV surface antigen).
15. Prior malignancy that required treatment, or has shown evidence of recurrence (except for non-melanoma skin cancer or adequately treated cervical carcinoma in situ) during the 5 years prior to enrollment. Cancer treated with curative intent > 5 years previously and without evidence of recurrence will be allowed.
16. Active GI dysfunction interfering with the ability to swallow tablets, or any GI dysfunction that could interfere with absorption of study treatment.
17. Grade = 3 peripheral neuropathy, and Grade = 2 painful neuropathy, within 21 days prior to Cycle 1 Day 1.
18. Serious, active psychiatric or medical conditions which, in the opinion of the Investigator, could interfere with treatment.
19. Participation in an investigational anti-cancer study within 21 days prior to Cycle 1 Day 1.
20. Receipt of transfusions as follows:
a. Platelet infusion within 1 week prior to Cycle 1 Day 1.
b. RBC transfusion within 2 weeks prior to Cycle 1 Day 1.
21. Receipt of the following blood growth factors within 2 weeks prior to Cycle 1 Day 1: Granulocyte colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor (GM-CSF), erythropoietin (EPO), or megakaryocyte growth factor.
22. Known intolerance to or contraindication for glucocorticoid therapy at Cycle 1 Day 1.
23. Prior exposure to a SINE compound, including Selinexor.
24. Unable or unwilling to comply with protocol requirements, including providing a 24-hour urine samples at the required study time points.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method