This is a prospective, 2-arm (with an additional exploratory arm), open-label, multicenter study looking at the response rate of patients receiving selinexor (KPT-330), in combination with carfilzomib, daratumumab or pomalidomide.
Multiple Myeloma patients with documented disease progression or refractory disease while on current treatment with any carfilzomib-containing regimen (arm 1), any pomalidomide-containing regimen (arm 2) or any daratumumab-containing regimen (exploratory arm) will be included in the study. Patients will be assigned to the respective groups according to their current treatment. If a subject has received more than one of the above therapies, then assignment will be made at their physician's discretion (e.g treatment decision can be made based upon patient and physician preferred tolerance.).
Patients will receive treatment until progressive disease (PD), death, toxicity that cannot be managed by standard of care, or withdrawal, whichever occurs first.
Age ≥18 years at time of informed consent.
Arm 1: Refractory to or disease progression while on a carfilzomib-containing regimen
Arm 2: Refractory to or disease progression while on a pomalidomide-containing regimen
Exploratory Arm: Refractory to or disease progression while on a daratumumab-containing regimen
Smoldering MM
Radiation therapy, chemotherapy or immunotherapy other than above stated regimens in #2 ≤2 weeks prior to C1D1. Patients on long-term glucocorticosteroids during screening do not require a washout period. Prior RT is permitted for treatment of fractures or to prevent fractures as well as for pain management.
Active graft versus host disease after allogeneic stem cell transplant.
Life expectancy <3 months.
Parallel
Selinexor 60 MG
DrugSelinexor 60 mg PO on days 1, 8 and 15
Selinexor 80 MG
DrugSelinexor 80 mg PO on days 1, 8 and 15
Selinexor 100 MG
DrugSelinexor 100 mg PO on days 1, 8, 15 and 22
Carfilzomib
Drug56 mg/m2 IV on days 1, 8 and 15
Pomalidomide
Drug4 mg PO daily for 21 days
Daratumumab
Drug16 mg/kg IV days 1, 8, 15 and 22 for cycles 1-2; days 1 and 15 for cycles 3-6; day 1 for cycle 7 and on
Dexamethasone
Drug20 mg if ≥ 75 years old and 40 mg if \< 75 years old on days 1, 8, 15 and 22
Overall Response Rate (ORR) of patients receiving selinexor with carfilzomib and dexamethasone (Arm 1)
ORR will include patients who experience partial response (PR), very good partial response (VGPR), complete response (CR), or stringent complete response (sCR), based on International Myeloma Working Group (IMWG) response criteria (Kumar 2016)
Overall Response Rate (ORR) of patients receiving selinexor with pomalidomide and dexamethasone (Arm 2)
ORR will include patients who experience partial response (PR), very good partial response (VGPR), complete response (CR), or stringent complete response (sCR), based on International Myeloma Working Group (IMWG) response criteria (Kumar 2016)
Progression Free Survival (PFS)
Duration from start of study treatment to PD or death \[regardless of cause\], whichever comes first
Overall Survival (OS)
Duration from start of study treatment to death
MRD Negativity
Rate of achievement of minimal residual disease (MRD) by multiparametric flow cytometry
Incidence of Adverse Events [Safety and Tolerability] using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), v 4.03.
Incidence of Adverse Events \[Safety and Tolerability\] using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), v 4.03.
Overall Response Rate (ORR) of patients receiving selinexor with daratumumab and dexamethasone
ORR will include patients who experience partial response (PR), very good partial response (VGPR), complete response (CR), or stringent complete response (sCR), based on International Myeloma Working Group (IMWG) response criteria (Kumar 2016)
Gut Microbiome analysis
To identify intestinal microbiota associated biomarkers that predict response and risk for development of treatment-related toxicities at baseline, on-treatment, post-treatment and relapse.
Immune cell subset analyses
Changes from baseline in immune cell subsets in peripheral blood mononuclear and bone marrow mononuclear cells will be monitored.
Analyses of cytokine markers
Cytokines will be quantified in plasma samples by multiplex ELISA and other readout assays.
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Hackensack Meridian Health
Lead sponsor
Karyopharm Therapeutics Inc
Collaborator
