Selinexor, Pomalidomide, and Dexamethasone With or Without Carfilzomib for the Treatment of Patients With Relapsed Refractory Multiple Myeloma, The SCOPE Trial
Phase 1/2 Trial of Selinexor in Combination With Pomalidomide and Dexamethasone ± Carfilzomib for Patients With Proteasome-Inhibitor and Immunomodulatory Drug Refractory Multiple Myeloma (SCOPE)
2 other identifiers
interventional
39
1 country
1
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started May 2021
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 17, 2021
CompletedFirst Posted
Study publicly available on registry
February 21, 2021
CompletedStudy Start
First participant enrolled
May 6, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 6, 2026
CompletedStudy Completion
Last participant's last visit for all outcomes
December 17, 2027
ExpectedFebruary 25, 2026
February 1, 2026
5 years
February 17, 2021
February 23, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
Maximum tolerated dose of selinexor in combination with carfilzomib, pomalidomide and dexamethasone (Phase I)
A standard 3+3 phase I design will be utilized. Three patients will be treated at each dose level and observed for a minimum of four weeks (i.e. one full cycle) before new patients are treated. Doses will not be escalated in any individual patient.
Up to 30 days after completion of treatment
Proportion of patients who achieve a confirmed response with selinexor in combination with pomalidomide and dexamethasone (Phase 2)
A confirmed response is defined as an stringent complete response (sCR), complete response (CR), very good \[partial response (VGPR), or partial response (PR) noted as the objective status on two consecutive evaluations. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Ninety-five percent confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.
Up to 3 years
Secondary Outcomes (5)
Duration of response
Up to 3 years
Clinical benefit rate
Up to 3 years
Overall survival
From registration to death due to any cause, assessed up to 3 years
Progression-free survival
From registration to the earliest date of documentation of disease progression, relapse, or death due to any cause, assessed up to 3 years
Incidence of adverse events
Up to 3 years
Other Outcomes (4)
Relationship between risk groups
Up to 3 years
Minimal residual disease (MRD)
Up to 3 years
Overall health-related quality of life
Up to 18 cycles (each cycle is 28 days)
- +1 more other outcomes
Study Arms (2)
Arm A (selinexor, dexamethasone, carfilzomib, carfilzomib)
EXPERIMENTALPatients receive selinexor PO and dexamethasone PO on days 1, 8 15, and 22, carfilzomib IV on days 1, 8, and 15, and pomalidomide PO on days 1-21. Treatment repeats every 28 days for up to 18 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo PET/CT or CT and bone marrow biopsy and aspiration during screening and on the trial. Patients may optionally undergo blood sample collection during screening and on the trial.
Arm B (selinexor, dexamethasone, pomalidomide)
EXPERIMENTALPatients receive selinexor PO and dexamethasone PO on days 1, 8, 15, and 22, and pomalidomide PO on days 1-21. Treatment repeats every 28 days for up to 18 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo PET/CT or CT and bone marrow biopsy and aspiration during screening and on the trial. Patients may optionally undergo blood sample collection during screening and on the trial.
Interventions
Given IV
Given PO
Given PO
Ancillary studies
Ancillary studies
Given PO
Undergo x-ray imaging
Undergo PET/CT
Undergo PET/CT
Undergo bone marrow biopsy and aspiration
Undergo bone marrow biopsy and aspiration
Undergo blood sample collection
Eligibility Criteria
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
- +16 more criteria
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
- +22 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Mayo Cliniclead
Study Sites (1)
Mayo Clinic in Rochester
Rochester, Minnesota, 55905, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Prashant Kapoor, M.D.
Mayo Clinic in Rochester
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 17, 2021
First Posted
February 21, 2021
Study Start
May 6, 2021
Primary Completion
May 6, 2026
Study Completion (Estimated)
December 17, 2027
Last Updated
February 25, 2026
Record last verified: 2026-02