A Phase I Study of the Combination of a Selective Inhibitor of Nuclear Export (SINE), Selinexor With Carfilzomib and Dexamethasone in Patients With Relapsed or Relapsed/Refractory Multiple Myeloma
This phase I trial studies the side effects and best dose of selinexor and carfilzomib when given together with dexamethasone in treating patients with multiple myeloma that has returned or does not respond to treatment. Drugs used in chemotherapy, such as selinexor and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving selinexor, carfilzomib, and dexamethasone may be a better treatment for multiple myeloma.
• Written informed consent in accordance with federal, local, and institutional guidelines
• Aged 18 years or older
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Diagnosis of multiple myeloma as per International Myeloma Working Group (IMWG) uniform criteria
• Measurable disease by IMWG as defined by at least one of the following:
‣ Serum M-protein \>= 0.5 g/dL
⁃ Urine M-protein \>= 200 mg in a 24-hour collection
⁃ Serum free light chain level \>= 10 mg/dL provided the free light chain ratio is abnormal
⁃ Measurable plasmacytoma; if plasmacytoma measurement is the only measurable disease, subject eligibility must be reviewed with lead principal investigator (PI) prior to signing consent
• Relapsed/refractory multiple myeloma with progressive disease at study entry
• Subjects must have been treated with at least 2 prior therapies including a proteasome inhibitor and a cereblon-binding agent
‣ Subjects who are refractory to carfilzomib may enroll throughout the trial; carfilzomib refractory status is defined by IMWG criteria: disease that is nonresponsive while on salvage therapy, or progresses within 60 days of last therapy in patients who have achieved minimal response (MR) or better at some point previously before then progressing in their disease course
• Ability to adhere with the study visit schedule and other protocol procedures
• Absolute neutrophil count (ANC) \>= 1.0 x 10\^9/L; screening ANC should be independent of growth factor support for over one week for all patients
• Hemoglobin \>= 8 g/dL; subjects may receive red blood cell transfusions as clinically indicated per institutional guidelines but screening hemoglobin should be independent of red blood cell transfusion for at least 3 days prior to cycle 1 day 1
• Platelet count \>= 50,000mm\^3; platelet count should be independent of transfusions for at least 14 days for eligibility
• Total bilirubin =\< 2 times the upper limit of normal (ULN) (except patients with Gilbert's syndrome who must have a total bilirubin of \< 3 times ULN)
• Alanine aminotransferase (ALT) =\< 2.5 times ULN; in the case of known (radiological and/or biopsy documented) liver metastasis, ALT =\< 2.5 times ULN is acceptable
• Estimated creatinine clearance of \>= 30 mL/min, calculated using the formula of Cockroft and Gault
• Female patients of child-bearing potential must agree practice abstinence or use dual methods of contraception during treatment and for 90 days after last dose of study drug.
• Female patients of child-bearing potential must have negative pregnancy test at screening
• Male patients must agree practice abstinence or use effective barrier methods of contraception during treatment and for 90 days after last dose of study drug
• Male patients must agree not to donate semen or sperm treatment and for 90 days after last dose of carfilzomib