Selinexor and Backbone Treatments of Multiple Myeloma Patients

Recruiting now · Phase 1/Phase 2

Conditions studied: Multiple Myeloma

In brief

This study will independently assess the efficacy and safety of 11 combination therapies in 12 arms, in dose-escalation/-evaluation and expansion phases, for the treatment of patients with relapsed/refractory multiple myeloma (RRMM) and newly diagnosed multiple myeloma (NDMM). The combinations to be evaluated are: * Arm 1: Selinexor + dexamethasone + pomalidomide (SPd); enrollment complete * Arm 2: Selinexor + dexamethasone + bortezomib (SVd); enrollment complete * Arm 3: Selinexor + dexamethasone + lenalidomide (SRd) in RRMM; enrollment complete * Arm 4: Selinexor + dexamethasone + pomalidomide + bortezomib (SPVd); enrollment complete * Arm 5: Selinexor + dexamethasone + daratumumab (SDd); enrollment complete * Arm 6: Selinexor + dexamethasone + carfilzomib (SKd); enrollment complete * Arm 7: Selinexor + dexamethasone + lenalidomide (SRd) in NDMM; enrollment complete * Arm 8: Selinexor + dexamethasone + ixazomib (SNd); enrollment complete * Arm 9: Selinexor + dexamethasone + pomalidomide + elotuzumab (SPEd); enrollment complete * Arm 10: Selinexor + dexamethasone + belantamab mafodotin (SBd); enrollment complete * Arm 11: Selinexor + dexamethasone + pomalidomide + daratumumab (SDPd); enrollment complete * Arm 12: Selinexor + dexamethasone + mezigdomide (SMd); actively recruiting Selinexor pharmacokinetics: * PK Run-in (Days 1-14): Starting in protocol version 8.0, patients enrolled to any arm in the Dose Escalation Phase (i.e., Arm 4 \[SPVd\], Arm 6 \[SKd\], Arm 8 \[SNd\], Arm 9 \[SPEd\], Arm 10 \[SBd\], and Arm 11 \[SDPd\]) will also first be enrolled to a pharmacokinetics (PK) Run-in period until 9 patients have been enrolled to this period to evaluate the PK of selinexor before and after co-administration with a strong CYP3A4 inhibitor. This run-in period does not apply to Arm 12 (SMd).

Key facts

Study ID: NCT02343042
Run by: Karyopharm Therapeutics Inc
People needed: 300
Starts: 2015-10-01
Expected to finish: 2027-04-01
Last updated by the study team: 2026-07-15

Who can join

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

You may qualify if…

Written informed consent signed in accordance with federal, local, and institutional guidelines.
Age greater than or equal to (≥) 18 years at the time of informed consent.
Histologically confirmed diagnosis with measurable disease for relapsed/refractory myeloma.
Symptomatic MM, based on IMWG guidelines.
Patients must have measurable disease as defined by at least one of the following:
Serum M-protein ≥ 0.5 gram per deciliter (g/dL) by serum protein electrophoresis (SPEP) or, for immunoglobulin A (IgA) myeloma, by quantitative IgA
Urinary M-protein excretion at least 200 mg/24 hours
Serum free light chain (FLC) ≥ 100 milligram per liter (mg/L), provided that FLC ratio is abnormal
If SPEP is felt to be unreliable for routine M-protein measurement (example, for IgA MM), then quantitative immunoglobulin (Ig) levels by nephelometry or turbidometry are acceptable
Any non-hematological toxicities (except for peripheral neuropathy as described in exclusion criterion #22) that patients had from treatments in previous clinical studies must have resolved to less than or equal (≤) Grade 2 by C1D1.
Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2.
Adequate hepatic function within 28 days prior to C1D1:
For SPd, SRd, and SPEd: Total bilirubin < 2* upper limit of normal (ULN) (except patients with Gilbert's syndrome [hereditary indirect hyperbilirubinemia] who must have a total bilirubin of ≤ 3* ULN) and both aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5* ULN
For SVd, SPVd, SDd, SNd, SBd and SDPd: Total bilirubin of < 1.5* ULN (except patients with Gilbert's syndrome [hereditary indirect hyperbilirubinemia] who must have a total bilirubin of ≤ 3* ULN) and both AST and ALT < 2.0* ULN
For SKd and SMd: Total bilirubin < 2x ULN (except patients with Gilbert's syndrome [hereditary indirect hyperbilirubinemia] who must have a total bilirubin of ≤ 3x ULN) and both AST and ALT < 3.0x ULN
Adequate renal function within 28 days prior to C1D1. For Arms 1-11, estimated creatinine clearance (CrCl) calculated using the formula of Cockroft and Gault (1976).
≥ 20 milliliter per minute (mL/min) for SVd, SDd, and SKd arms
≥ 30 mL/min for SNd, SBd, and SMd arms
≥ 45 mL/min for SPd, SPVd, SPEd and SDPd arms
> 60 mL/min for SRd arm
Adequate hematopoietic function within 28 days prior to C1D1: absolute neutrophil count (ANC) ≥ 1,000/mm\^3, hemoglobin (Hb) ≥ 8.0 g/dL, and platelet count ≥ 100,000/mm\^3.
SPVd (Arm 4) and SKd (Arm 6) only: platelet count ≥150,000.
SMd (Arm 12) only: platelet count ≥75,000 for subjects in whom <50% of bone marrow nucleated cells are plasma cells; or platelet count <50,000 for subjects in whom ≥50% of bone marrow nucleated cells are plasma cells.
Female patients of childbearing potential must have a negative serum pregnancy test at Screening. Female patients of childbearing potential and fertile male patients must use highly effective methods of contraception throughout the study and for 90 days following the last dose of study treatment. For Arm 12 (SMd), all study subjects must agree and adhere to all testing and contraception requirements as specified in the mezigdomide Global Pregnancy Prevention Plan (PPP)
SPd (Arm 1) Only.

You may not qualify if…

Patients meeting any of the following exclusion criteria are not eligible to enroll in this study:
Smoldering MM.
MM that does not express M-protein or FLC (i.e., non-secretory MM is excluded), and quantitative immunoglobulin levels cannot be used instead.
Documented active systemic amyloid light chain amyloidosis.
Active plasma cell leukemia.
Red Blood Cell (RBC) and platelet transfusions and blood growth factors within 14 days of C1D1 (Arms 1-11 only). Red blood cells and platelet transfusions and blood growth factors within 7 days of C1D1 (Arm 12).
Platelet transfusion or G-CSF within 7 days or pegfilgastrim within 14 days prior to the complete blood count (CBC) used to determine eligibility.
Radiation, chemotherapy, or immunotherapy or any other tumor-directed therapy ≤ 2 weeks prior to C1D1, and radio-immunotherapy within 6 weeks prior to C1D1. Patients on long-term glucocorticoids during Screening do not require a washout period. Spot radiation is permitted at any time for treatment of fractures or to prevent fractures as well as for pain management.
Patients with history of spinal cord compression with residual paraplegia (Dose Escalation Phase only).
Treatment with an investigational anti-cancer therapy within 3 weeks prior to C1D1.
Prior autologous stem cell transplantation < 1 month, or allogeneic stem cell transplantation < 3 months prior to C1D1.
Active graft versus host disease after allogeneic stem cell transplantation.
Life expectancy < 3 months.
Major surgery within 4 weeks prior to C1D1.
Active, unstable cardiovascular function:
Symptomatic ischemia, or
Uncontrolled clinically-significant conduction abnormalities (e.g., patients with ventricular tachycardia on antiarrhythmics are excluded; patients with 1st degree atrioventricular (AV) block or asymptomatic left anterior fascicular block/right bundle branch block (LAFB/RBBB) will not be excluded), or
Congestive heart failure (CHF) of New York Heart Association (NYHA) Class ≥ 3, or
Myocardial infarction (MI) within 3 months prior to C1D1
Ejection fraction (EF) < 50% at Screening (Arms 1-11 only, screening echocardiogram not required for Arm 12, SMd)
Uncontrolled active hypertension (Arms 1-11 only).
Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose.
Known active hepatitis A, B or C.
Known human immunodeficiency virus (HIV) infection or HIV seropositivity.
Any active gastrointestinal dysfunction that prevents the patient from swallowing tablets or interferes with absorption of study treatment.

Where it is running

Fred Hutch Cancer Center — Seattle, Washington, United States (enrolling)
Duke Institute of Cancer/ Duke University — Durham, North Carolina, United States (enrolling)
Dana Farber Cancer Institute — Boston, Massachusetts, United States (enrolling)
Massachusetts General Hospital — Boston, Massachusetts, United States
University of Nebraska Medical Center — Omaha, Nebraska, United States
Hackensack University Medical Center - John Theurer Cancer Center — Hackensack, New Jersey, United States
Columbia University — New York, New York, United States
Weill Cornell Medicine — New York, New York, United States
Wilmot Cancer Center/ University of Rochester — Rochester, New York, United States
University of North Carolina - Chapel Hill Comprehensive Cancer Center — Chapel Hill, North Carolina, United States
Sarah Cannon- Tennessee Oncology Nashville — Nashville, Tennessee, United States
Swedish Cancer Institute — Seattle, Washington, United States
University of Wisconsin School of Medicine and Public Health — Madison, Wisconsin, United States
Tom Baker Cancer Center/Alberta Health Services — Calgary, Alberta, Canada
Cross Cancer Institute / University of Alberta — Edmonton, Alberta, Canada
Vancouver General Hospital — Vancouver, British Columbia, Canada
Cancer Care Manitoba — Winnipeg, Manitoba, Canada
Memorial Hospital of Newfoundland — St. John's, Newfoundland and Labrador, Canada
Queen Elizabeth II Health Sciences Center — Halifax, Nova Scotia, Canada
Princess Margaret Cancer Centre — Toronto, Ontario, Canada
Maisonneuve-Rosemont Hospital — Montreal, Quebec, Canada
Banner MD Anderson Cancer Center — Gilbert, Arizona, United States
Royal Victoria Hospital / McGill University — Montreal, Quebec, Canada
Jonnsson Comprehensive Cancer Center / University of Los Angeles — Los Angeles, California, United States
Sarah Cannon-Colorado Blood Cancer Institute — Denver, Colorado, United States

Full record on ClinicalTrials.gov

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