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

NCT02199665 | Completed Phase 1 DMC

• 3 other identifiers: IRB14-0033NCI-2014-01199P30CA014599
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 5

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.

Conditions

Refractory Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of selinexor, carfilzomib, and dexamethasone

  Defined as the dose level below the dose in which greater than or equal to 2 out of 6 patients experience dose limiting toxicity. Will be assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

  28 days

Secondary Outcomes (3)

• Incidence of toxicities related to the combination of selinexor and carfilzomib assessed using NCI CTCAE version 4.0

  Up to 28 days after completion of study treatment

• Efficacy as measured by stable disease or better (including MR, partial response, very good partial response, complete response and stringent complete response) according to IMWG criteria

  Up to 2 years

• Incidence of toxicities assessed using NCI CTCAE version 4.0

  Up to 28 days after completion of study treatment

Study Arms (1)

Selinexor, carfilzomib, dexamethasone

EXPERIMENTAL

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.

Drug: selinexor; Drug: carfilzomib; Drug: dexamethasone

Interventions

selinexor DRUG

Given PO

Also known as: CRM1 nuclear export inhibitor KPT-330, KPT-330, selective inhibitor of nuclear export KPT-330, SINE KPT-330

Selinexor, carfilzomib, dexamethasone

carfilzomib DRUG

Given IV

Also known as: Kyprolis, PR-171

Selinexor, carfilzomib, dexamethasone

dexamethasone DRUG

Given PO or IV

Also known as: Aeroseb-Dex, Decaderm, Decadron, DM, DXM

Selinexor, carfilzomib, dexamethasone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Chicago: lead
• National Cancer Institute (NCI): collaborator

Study Sites (5)

Mayo Clinic (AZ)

Scottsdale, Arizona, 85259, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Wayne State University Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

Related Publications (1)

• 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.

  PMID: 31124580 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

selinexor; carfilzomib; Dexamethasone; Calcium Dobesilate

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• Andrzej Jakubowiak

  University of Chicago

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 22, 2014
• First Posted: July 24, 2014
• Study Start: June 12, 2014
• Primary Completion: October 1, 2025
• Study Completion: October 25, 2025
• Last Updated: November 3, 2025

Record last verified: 2025-09

Locations

US (5)