Selinexor, Pomalidomide, and Dexamethasone With or Without Carfilzomib for the Treatment of Patients With Relapsed Refractory Multiple Myeloma, The SCOPE Trial

Running, not enrolling · Phase 1/Phase 2

Conditions studied: Recurrent Multiple Myeloma, Refractory Multiple Myeloma

In brief

This phase I/II trial identifies the best dose and side effects of selinexor, and how well it works when given in combination with pomalidomide and dexamethasone with or without carfilzomib in treating patients with multiple myeloma that has come back (relapsed) and does not respond to treatment with proteasome inhibitors and immunomodulatory drugs (refractory). Selinexor is an oral agent that blocks a protein called Exportin 1 (XPO1 or CRM1) that is abundant in a wide variety of cancers, including multiple myeloma. Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Pomalidomide may stop the growth of blood vessels, stimulate the immune system, and kill cancer cells. Anti-inflammatory drugs, such as dexamethasone may lower the body's immune response and are used with other drugs in the treatment of some types of cancer. The addition of selinexor may allow better control of relapsed refractory multiple myeloma than is possible with pomalidomide and dexamethasone with or without carfilzomib.

Key facts

Study ID

NCT04764942

Run by

Mayo Clinic

People needed

39

Starts

2021-05-06

Expected to finish

2027-12-17

Last updated by the study team

2026-02-25

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Age >= 18 years
• Diagnosis of RRMM with progressive disease at study entry as per the International Myeloma Working Group (IMWG) uniform criteria
• Measurable disease by IMWG criteria 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
• For patients with extramedullary measurable disease (EMD) by CT or MRI or the CT portion of the PET/CT: Must have at least one lesion that has a single diameter of >= 2 cm. Skin lesions can be used if the area is >= 2cm in at least one diameter and measured with a ruler
• Bone marrow plasma cells >= 30%
• Patients with IgA myeloma in whom serum protein electrophoresis is deemed unreliable, due to co-migration of normal serum proteins with the para protein in the beta region, may be considered eligible as long as total serum IgA level is elevated above normal range
• Prior treatment:
• Arm A: At least one of the following must be true: (1) Subjects must have been previously treated with at least 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory drug (IMiD) (2) Subjects who are refractory to carfilzomib and/or pomalidomide may enroll in Arm A using the quadruplet regimen, SKPd, provided carfilzomib, pomalidomide and dexamethasone (KPd) triplet is not the most recent line of prior therapy and that they have been previously treated with at least 3 prior lines of therapy, including a proteasome inhibitor and an IMiD. Carfilzomib/Pomalidomide refractory status is defined by the IMWG criteria: disease that is nonresponsive (stable disease [SD] or progressive disease [PD]) while on 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.
• Arm B: Subjects must have progressive disease and been exposed to up to 2 prior lines of therapy, including a proteasome inhibitor and lenalidomide
• Provide written informed consent
• Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study) and ability to adhere with the study visit schedule and other protocol procedures
• Willingness to provide mandatory tissue specimens for correlative research
• Willingness to use fixed-duration therapy (up to 18 cycles) for relapsed refractory multiple myeloma
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
• Ability to complete questionnaire(s) by themselves or with assistance
• Willingness to provide mandatory blood specimens for correlative research
• Calculated creatinine clearance (using Cockcroft-Gault equation) >= 15 mL/min (obtained =< 14 days prior to registration)
• Absolute neutrophil count (ANC) >= 1500/uL(without growth factor support for >= 7 days ( obtained =< 14 days prior to registration)
• Un-transfused Platelet count >= 100,000/uL (without platelet transfusion for >= 14 days) for SKPd and >= 100,000 (without platelet transfusion for >= 7 days) for SPd is permitted. Additionally, for both Arms A and B platelet count of >= 75,000/uL is permitted if thrombocytopenia is deemed by the investigator to be secondary to severe bone marrow infiltration (>= 50%) by myeloma as determined
• Hemoglobin >= 8.0 g/dL Note: Screening hemoglobin should be independent of red blood cell transfusion for at least 3 days prior to screening
• Total bilirubin =< 2.0 x upper limit of normal (ULN). Note: Patients with Gilbert's syndrome who must have a total bilirubin of < 3 times ULN
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN

You may not qualify if…

• History of myocardial infarction =< 6 months prior to pre-registration, or congestive heart failure requiring use of ongoing maintenance therapy for life threatening ventricular arrhythmias. Unstable angina 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, corrected QT (QTc) interval >= 470 msec, 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
• Failure to recover from acute, reversible effects of prior therapy regardless of interval since last treatment.
• EXCEPTION: Grade 1 peripheral (sensory) neuropathy that has been stable for at least 1 month since completion of prior treatment
• Uncontrolled intercurrent non-cardiac illness including, but not limited to:
• Ongoing or active infection. Uncontrolled infection requiring parenteral antibiotics, antivirals, or antifungals =< 14 days prior to registration; patients with controlled infection or on prophylactic antibiotics are permitted in the study
• Psychiatric illness/social situations
• Dyspnea at rest due to complications of advanced malignancy or other disease that requires continuous oxygen therapy
• Any other conditions that would limit compliance with study requirements
• Patients known to be human immunodeficiency virus (HIV) positive and/or currently receiving antiretroviral therapy
• Currently receiving any other investigational agent which would be considered as a treatment for RRMM
• Non investigational radiation, chemotherapy, or immunotherapy or any other anticancer therapy =< 14 days or five half-lives, whichever is shorter prior to registration. Note: (localized radiation to a single site =< 7 days prior to registration is allowed)
• Participation in an investigational anti-cancer study =< 21 days or five half-lives whichever is shorter prior to registration
• Major Surgery =< 21 days prior to registration
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
• Other active malignancy =< 5 years prior to registration. EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix that has undergone potentially curative therapy. NOTE: If there is a history of prior malignancy, they must not be receiving other specific treatment for their cancer
• Uncontrolled hypertension or uncontrolled diabetes =< 14 days prior to registration
• Known active hepatitis A, B, or C infection; or known to be positive for hepatitis C virus (HCV) ribonucleic acid (RNA) or hepatitis B surface antigen (HBsAg) [hepatitis B virus (HBV) surface antigen]
• Significant neuropathy (grades 3-4, or grade 2 with pain) =< 14 days prior to registration
• 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
• 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 =< 14 days prior to registration
• Patients with coagulation problems and active bleeding in the last month (e.g, peptic ulcer, epistaxis, spontaneous bleeding)
• Subjects with smoldering multiple myeloma (SMM), monoclonal gammopathy of undetermined significance (MGUS) or Waldenström's macroglobulinemia or AL amyloidosis
• History of repeated infections, hyperviscosity or POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)

Where it is running

• Mayo Clinic in Rochester — Rochester, Minnesota, United States

Full record on ClinicalTrials.gov

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