This study is a single institution, open-label phase II study to evaluate the overall
response rate achieved with selinexor and dexamethasone based three drug combination therapy,
selected by physician's choice, in patients with relapsed/refractory multiple myeloma.
Patients with RRMM will be eligible for enrollment. During screening, in addition to standard
of care disease assessments, participant's bone marrow aspirate will be evaluated using a
novel ex vivo Myeloma Drug Sensitivity Testing platform (My-DST). The following agents will
be eligible for physician's choice, and in parallel evaluated for sample sensitivity in
MyDST: pomalidomide, carfilzomib and daratumumab. Agents will be tested individually, in
combination with selinexor and in combination with selinexor and dexamethasone. Results from
MyDST will be not be available to investigators at time of treatment assignment, but will be
evaluated to better characterize test performance and relationship with treatment outcomes.
Investigators will assign patients to one of the following treatment combinations:
Selinexor/Pomalidomide/Dexamethsone (SPd), Selinexor/Daratumumab/Dexamethasone (SDd) or
Selinexor/Carfilzomib/Dexamethasone (SKd). Investigators will use patient specific
considerations such as prior therapeutic exposures, response to / tolerance of prior
therapies and comorbid conditions which may increase risk for toxicity with specific agents
to guide expert judgement in selecting partner agent for selinexor and dexamethasone.
Treatment will continue until progression of disease, unacceptable toxicity or death.
This study will evaluate if physician's choice partner drug selection for selinexor based
combination therapy in RRMM will lead to an overall response rate of 75% or higher.
Inclusion Criteria:
1. Age ≥ 18 years
2. Willing and able to provide written informed consent in accordance with federal,
local, and institutional guidelines. The patient must provide informed consent prior
to the first screening procedure.
3. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of ≤ 2
4. Histologically confirmed diagnosis, measurable disease and evidence of disease
progression of MM after 1 or more prior lines of therapy with either of the following:
1. Documented evidence of PD after achieving at least SD for ≥ 1 cycle during a
previous MM regimen (i.e., relapsed MM)
2. ≤ 25% response (i.e, patient never achieved ≥ MR) or PD during or within 60 days
from end of the most recent MM regimen (i.e., refractory MM)
5. Patients must have measurable disease as defined by at least one of the following:
1. Serum M-protein ≥ 0.5 g/dL by serum protein electrophoresis (SPEP) or, for IgA
myeloma, by quantitative IgA
2. Urinary M-protein excretion at least 200 mg/24 hours
3. Serum FLC ≥ 10 mg/dL, provided that FLC ratio is abnormal
4. If no measurable disease by serum or urine, then the presence of a plasmacytoma
of ≥2cm in one dimension prior to start of study can be used to follow response
via radiologic imaging.
6. Adequate hepatic function:
1. Total bilirubin < 1.5 × upper limit of normal (ULN) (except patients with
Gilbert's syndrome who must have a total bilirubin of < 3 × ULN), and
2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) normal to
<2.5 × ULN.
7. Adequate renal function as determined by serum creatinine of ≤2 mg/dL OR estimated
creatinine clearance of ≥ 20 mL/min, calculated using the Cockcroft and Gault formula
(140 - Age) • Mass (kg)/ (72 • creatinine mg/dL); multiply by 0.85 if female
(Cockcroft 1976).
8. Adequate hematopoietic function within 7 days prior to C1D1: absolute neutrophil count
≥1000/mm3, hemoglobin ≥8 g/dL and platelet count ≥100,000/mm3 (patients for whom <50%
of bone marrow nucleated cells are plasma cells) or ≥50,000/mm3 (patients for whom
≥50% of bone marrow nucleated cells are plasma cells).
1. Patients may receive hematopoietic growth factor support, including
erythropoietin, darbepoetin, granulocyte-colony stimulating factor (G-CSF),
granulocyte macrophage-colony stimulating factor (GM-CSF), and platelet
stimulators (eg, eltrombopag, romiplostim, or interleukin-11) at any time.
2. Patients may receive RBC and/or platelet transfusions as clinically indicated per
institutional guidelines during the study.
9. Female patients of childbearing potential must have a negative serum pregnancy test at
Screening. Female patients of childbearing potential and fertile male patients who are
sexually active with a female of childbearing potential must use highly effective
methods of contraception throughout the study and for 3 months following the last dose
of study treatment.
Exclusion Criteria:
1. Has received selinexor or another SINE (Specific Inhibitor of Nuclear Export) compound
in a previous line of therapy.
2. Has any concurrent medical condition or disease (eg, uncontrolled active hypertension,
uncontrolled active diabetes, active systemic infection, etc.) that is likely to
interfere with study procedures.
3. Uncontrolled active infection requiring parenteral antibiotics, antivirals, or
antifungals within 1 week prior to Cycle 1 Day 1 (C1D1). Patients on prophylactic
antibiotics or with a controlled infection within 1 week prior to C1D1 are acceptable.
4. Known intolerance, hypersensitivity, or contraindication to study drugs.
5. Pregnant or breastfeeding females.
6. Major surgery within 4 weeks prior to C1D1.
7. Active, unstable cardiovascular function, as indicated by the presence of:
1. Symptomatic ischemia, or
2. Uncontrolled clinically significant conduction abnormalities (eg, patients with
ventricular tachycardia on anti-arrhythmics are excluded; patients with first
degree atrioventricular block or asymptomatic left anterior fascicular
block/right bundle branch block will not be excluded), or
3. Congestive heart failure of New York Heart Association Class ≥3 or known left
ventricular ejection fraction <40%, or
4. Myocardial infarction within 3 months prior to C1D1.
8. Subjects with active hepatitis B virus (Hep B) are allowed if antiviral therapy for
hepatitis B has been given for >8 weeks and viral load is <100 IU/ml prior to first
dose of trial treatment. Subjects with untreated hepatitis C virus (HCV) are allowed.
Subjects with Human Immunodeficiency Virus (HIV) who have CD4+ T-cell counts ≥ 350
cells/µL and no history of AIDS-defining opportunistic infections in the last year are
allowed.
9. Any active gastrointestinal dysfunction interfering with the patient's ability to
swallow tablets, or any active gastrointestinal dysfunction that could interfere with
absorption of study treatment, including prior gastric bypass or bowel resection
procedures.
10. Inability or unwillingness to take supportive medications such as anti-nausea and
anti-anorexia agents as recommended by the National Comprehensive Cancer Network®
(NCCN) Clinical Practice Guidelines in Oncology (CPGO) (NCCN CPGO) for antiemesis and
anorexia/cachexia (palliative care).
11. Any active, serious psychiatric, medical, or other conditions/situations that, in the
opinion of the Investigator, could interfere with treatment, compliance, or the
ability to give informed consent.
12. Contraindication to any of the required concomitant drugs or supportive treatments.
13. Patients unwilling or unable to comply with the protocol, including providing 24-hour
urine samples for urine protein electrophoresis at the required time points.
