Selinexor, Carfilzomib, and Dexamethasone in Treating Patients With Relapsed or Refractory Multiple Myeloma

NCT ID: NCT02199665

Last Updated: 2025-11-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 52 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-06-12
• Study Completion Date: 2025-10-25

Brief Summary

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.

Detailed Description

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose (MTD) and the recommended phase II dose (RP2D) of the combination of selinexor, carfilzomib, and dexamethasone in relapsed and relapsed/refractory multiple myeloma.

SECONDARY OBJECTIVES:

I. Determine safety and tolerability.

II. Determine the efficacy, as measured by the rates of stable disease or better (including minimal response, partial response, very good partial response, complete response, and stringent complete response).

OUTLINE: This is a dose-escalation study of selinexor and carfilzomib.

Patients receive selinexor orally (PO), carfilzomib intravenously (IV), and dexamethasone PO QD or IV. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 3 months for 2 years.

Conditions

Refractory Multiple Myeloma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Selinexor, carfilzomib, dexamethasone

Patients receive selinexor PO, carfilzomib IV, and dexamethasone PO QD or IV. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

selinexor

Intervention Type: DRUG

Given PO

carfilzomib

Intervention Type: DRUG

Given IV

dexamethasone

Intervention Type: DRUG

Given PO or IV

Interventions

selinexor

Given PO

Intervention Type: DRUG

carfilzomib

Given IV

Intervention Type: DRUG

dexamethasone

Given PO or IV

Intervention Type: DRUG

Other Intervention Names

CRM1 nuclear export inhibitor KPT-330; KPT-330; selective inhibitor of nuclear export KPT-330; SINE KPT-330; Kyprolis; PR-171; Aeroseb-Dex; Decaderm; Decadron; DM; DXM

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• Patients who are pregnant or lactating
• Radiation, chemotherapy, or immunotherapy or any other anticancer therapy =< 2 weeks prior to cycle 1 day 1
• Concurrent therapy with approved or investigational anticancer therapeutic other than steroids
• Major surgery within four weeks before cycle 1 day 1
• Unstable angina or myocardial infarction within 4 months prior to randomization, New York Heart Association (NYHA) class III or IV heart failure, left ventricular ejection fraction (LVEF) < 40%, uncontrolled angina, history of severe coronary artery disease, severe uncontrolled ventricular arrhythmias including uncontrolled chronic atrial fibrillation/atrial flutter, history of torsades de pointe, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or grade 3 conduction system abnormalities unless subject has a pacemaker
• Subject has plasma cell leukemia or Waldenstrom's macroglobuleinemia or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) or amyloidosis
• Uncontrolled hypertension or uncontrolled diabetes within 14 days prior to randomization
• Uncontrolled infection requiring parenteral antibiotics, antivirals, or antifungals within 14 days prior to first dose; patients with controlled infection or on prophylactic antibiotics are permitted in the study
• Known to be human immunodeficiency virus (HIV) seropositive
• Known active hepatitis A, B, or C infection; or known to be positive for hepatitis C virus (HCV) ribonucleic acid (RNA) or HBsAg (hepatitis B virus [HBV] surface antigen)
• Non-hematologic malignancy within the past 3 years with the exception of a) adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b) carcinoma in situ of the cervix or breast; c) prostate cancer of Gleason grade 6 or less with stable prostate-specific antigen levels; or d) cancer considered cured by surgical resection or unlikely to impact survival during the duration of the study, such as localized transitional cell carcinoma of the bladder or benign tumors of the adrenal or pancreas
• Patients with markedly decreased visual acuity in the opinion of the treating investigator after completion of screening ophthalmologic exam
• Significant neuropathy (grades 3-4, or grade 2 with pain) within 14 days prior to randomization
• Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize carfilzomib)
• Any underlying condition that would significantly interfere with the absorption of an oral medication
• Serious psychiatric or medical conditions that could interfere with treatment
• Contraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity to all anticoagulation and antiplatelet options, antiviral drugs, or intolerance to hydration due to preexisting pulmonary or cardiac impairment
• Subjects with pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to randomization
• Patients with coagulation problems and active bleeding in the last month prior to cycle 1 day 1 (peptic ulcer, epistaxis, spontaneous bleeding)
• Previous Selinexor exposure

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

University of Chicago

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Andrzej Jakubowiak

Role: PRINCIPAL_INVESTIGATOR

University of Chicago

Locations

Mayo Clinic (AZ)

Scottsdale, Arizona, United States

University of Chicago

Chicago, Illinois, United States

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Wayne State University Karmanos Cancer Institute

Detroit, Michigan, United States

Mount Sinai Medical Center

New York, New York, United States

Countries

United States

References

Jakubowiak AJ, Jasielec JK, Rosenbaum CA, Cole CE, Chari A, Mikhael J, Nam J, McIver A, Severson E, Stephens LA, Tinari K, Rosebeck S, Zimmerman TM, Hycner T, Turowski A, Karrison T, Zonder JA. Phase 1 study of selinexor plus carfilzomib and dexamethasone for the treatment of relapsed/refractory multiple myeloma. Br J Haematol. 2019 Aug;186(4):549-560. doi: 10.1111/bjh.15969. Epub 2019 May 24.

Reference Type: DERIVED

PMID: 31124580 (View on PubMed)

Other Identifiers

NCI-2014-01199

Identifier Type: REGISTRY

Identifier Source: secondary_id

IRB14-0033

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA014599

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB14-0033

Identifier Type: -

Identifier Source: org_study_id