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

Summary

Participation Requirements

Description

PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) of selinexor in combination with carfilzomib, pomalidomide and dexamethasone (SKPd) in patients with relapsed refractory multiple myeloma (RRMM). (Arm A) II. To determine the efficacy of fixed-dose selinexor in combination with low...

PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) of selinexor in combination with carfilzomib, pomalidomide and dexamethasone (SKPd) in patients with relapsed refractory multiple myeloma (RRMM). (Arm A) II. To determine the efficacy of fixed-dose selinexor in combination with low-dose pomalidomide and dexamethasone (SPd) in patients with RRMM as measured by the overall response rate (ORR) per the International Myeloma Working Group (IMWG) criteria. (Arm B) SECONDARY OBJECTIVES: I. To evaluate the preliminary efficacy of SKPd in relapsed/refractory multiple myeloma, as measured by the overall response rate (ORR) per International Myeloma Working Group (IMWG) criteria and the duration of response (DOR). (Arm A) II. To evaluate clinical benefit rate (CBR), duration of response, progression-free survival, overall survival, and the safety profile of SPd. (Arm B) EXPLORATORY OBJECTIVES: I. To estimate clinical activity in different risk groups by cytogenetics. II. To assess minimal residual disease by flow cytometry in patients achieving complete response (CR) and compare the outcomes of patients who are serum mass-fix (mass spectrometry-based methodology available at Mayo Clinic) negative only versus those who have no evidence of disease by mass fix and flow-cytometry-based minimal residual disease (MRD). III. To assess overall health-related quality of life, as measured by the global health domain of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire and Quality of Life Questionnaire-Multiple Myeloma 20 (QLQ-MY20). IV. To evaluate patient reported outcomes using the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (Patient Reported Outcomes Version of Common Terminology Criteria for Adverse Events [PRO-CTCAE]). V. To stratify patients in arm A based on quadruple/penta-refractory status and to assess the impact of this stratification on patient outcomes. VI. To stratify patients in arm B based on their dual-refractory status and to assess the impact of this stratification on patient outcomes. OUTLINE: Patients with >= 3 prior lines of therapy are assigned to Arm A, while patients with 1-2 prior lines of therapy are assigned to Arm B. Arm A is a phase I dose-escalation study of selinexor and carfilzomib, with fixed-dose dexamethasone and pomalidomide followed by a dose-expansion study. Arm B is a phase II fixed-dose study of selinexor, dexamethasone, and pomalidomide. ARM A: Patients receive selinexor orally (PO) and dexamethasone PO on days 1, 8 15, and 22, carfilzomib intravenously (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. ARM B: Patients 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. After completion of study treatment, patients are followed up at 30 days, then every 3 months until progressive disease (PD) or subsequent treatment, then every 6 months until 3 years from registration.

Tracking Information