None listed
Conditions
Brief summary
The purpose of this study is to determine whether the combination of Selinexor and Dexamethasone combined improves response to treatment. Who is it for? You may be eligible to participate in this trial if you are aged 18 years or over, you have been diagnosed with either central nervous system (CNS) diffuse large B cell lymphoma (DLBCL) or myeloma. Study Details Eligible participants will receive Selinexor and Dexamethasone. Treatment (each cycle is 28 days) will be given until disease progression, unacceptable toxicity, or withdrawal of consent. Participants will be required to have blood samples taken at the beginning of each cycle along with a medical exam in order for researchers to monitor whether the treatment is safe and whether it is effectively treating the myeloma. It is hoped that the findings of this trial will establish the benefits of this combination for patients with central nervous system (CNS) diffuse large B cell lymphoma (DLBCL) and myeloma.
Interventions
All patients (10 patients with central nervous system (CNS) diffuse large B cell lymphoma (DLBCL) and 10 patients with CNS myeloma) will be administered the following treatment at the same time in a 28-day (4 weeks) cycle:
Selinexor 80mg orally weekly
Dexamethasone 40mg orally weekly (20mg for patients >75 years)
Treatment will be given until disease progression or unacceptable toxicity, withdrawal of consent whichever occurs first. Adherence is monitored through hospital drug administration r
All patients (10 patients with central nervous system (CNS) diffuse large B cell lymphoma (DLBCL) and 10 patients with CNS myeloma) will be administered the following treatment at the same time in a 28-day (4 weeks) cycle: Selinexor 80mg orally weekly Dexamethasone 40mg orally weekly (20mg for patients >75 years) Treatment will be given until disease progression or unacceptable toxicity, withdrawal of consent whichever occurs first. Adherence is monitored through hospital drug administration records and tablet adherence through drug packet return.
Sponsors
Australasian Myeloma Research Consortium
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age 18 years old or older 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) equal to or less than 2 4. Patients with relapsed/refractory CNS lymphoma according to the current World Health Organization classification, having had 1 line of induction treatment or more with no clinically-appropriate viable alternative options available. Patients with synchronous systemic involvement may be eligible after discussion with the CPI. 5. Patients with CNS multiple myeloma according to the current World Health Organization classification, with no clinically-appropriate alternative treatment available. Patients with systemic involvement are eligible. 6. Patients should have measurable CNS disease on imaging/scans, or leptomeningeal disease evident on CSF analysis via lumbar punctures. 7. Treatment with radiotherapy, chemotherapy, immunotherapy, immunosuppressive therapy, or any investigational agent for the purposes of treating cancer within 2 weeks prior to first study treatment 8. Treatment with monoclonal antibodies for the purposes of treating cancer within 4 weeks prior to first study treatment 9. Adequate hepatic function within 28 days prior to C1D1: a. total bilirubin equal to or less than 1.5 × upper limit of normal (ULN) (except patients with Gilbert’s syndrome who must have a total bilirubin of equal to or less than 3 × ULN), and b. aspartate aminotransferase (AST) and alanine aminotransferase (ALT) normal to equal to or less than 2 × ULN. 10. Adequate renal function within 28 days prior to C1D1 as determined by serum creatinine of equal to or less than 132 µmol/L OR estimated creatinine clearance of equal to or greater than 30 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). 11. Adequate hematopoietic function within 7 days prior to C1D1: a. total white blood cell (WBC) count equal to or greater than 1.5 x 10^9/L , b. absolute neutrophil count equal to or greater than 1.0 x 10^9/L c. hemoglobin equal to or greater than 85 g/L and d. platelet count equal to or greater than 75 x 10^9/L (patients for whom <50% of bone marrow nucleated cells are plasma cells) or equal to or greater than 50 10^9/L (patients for whom equal to or greater than 50% of bone marrow nucleated cells are plasma cells). 12. Patients receiving 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) must have a 2-week interval between growth factor support and the Screening assessments, but they may receive growth factor support during the study. 13. Patients must have at least a 2-week interval from the last red blood cell (RBC) and/or platelet transfusion prior to the Screening hemoglobin assessment (Patients may receive RBC and/or platelet transfusions as clinically indicated per institutional guidelines during the study.) 14. 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. 15. For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as defined below: With a female partner of childbearing potential or pregnant female partners, men must remain abstinent or use a condom plus an additional contraceptive method.
Exclusion criteria
1. Has received selinexor or another XPO1 inhibitor previously. 2. Prior malignancy that required treatment or has shown evidence of recurrence (except for non-melanoma skin cancer or adequately treated cervical carcinoma in situ) during the 5 years prior to randomization. Cancer treated with curative intent for >5 years previously and without evidence of recurrence will be allowed. 3. 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. 4. 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. 5. Known intolerance, hypersensitivity, or contraindication to glucocorticoids. 6. Pregnant or breastfeeding females. 7. Life expectancy of less than 12 weeks. 8. Major surgery within 4 weeks prior to C1D1. 9. Active, unstable cardiovascular function, as indicated by the presence of: a) Symptomatic ischemia, or b) 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 c) Congestive heart failure of New York Heart Association Class equal to or greater than 3 or known left ventricular ejection fraction less than 40%, or d) Myocardial infarction within 3 months prior to C1D1. 10. Known active human immunodeficiency virus (HIV) infection or HIV seropositivity. 11. Known active hepatitis A, B, or C infection; or known to be positive for hepatitis C virus ribonucleic acid (RNA) or hepatitis B virus surface antigen. 12. 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. 13. 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). 14. 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. 15. Contraindication to any of the required concomitant drugs or supportive treatments. 16. Patients unwilling or unable to comply with the protocol requirements 17. Previous hypersensitivity to selective inhibitor of nuclear export (SINE) drugs.
Outcome results
None listed