Relapsed/Refractory DLBCL MedDRA version: 20.0 Level: HLT Classification code 10012819 Term: Diffuse large B-cell lymphomas System Organ Class: 100000004851
Conditions
Interventions
Product Name: Selinexor 20mg coated tablets
Product Code: KPT-330
Pharmaceutical Form: Coated tablet
INN or Proposed INN: Selinexor
CAS Number: 1393477-72-9
Current Sponsor code: KPT-330
Concentration
Sponsors
Karyopharm Therapeutics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: The study population under evaluation will consist of male and female patients aged 18 years or older. To be included in this study, a patient must meet all the following criteria: 1. Written informed consent in accordance with federal, local, and institutional guidelines. The patient must provide informed consent prior to the first screening procedure. 2. Age =18 years 3. Eastern Cooperative Oncology Group (ECOG) performance status of = 2 (Appendix 2) 4. Patients should have estimated life expectancy of >3 months at study entry 5. Previously treated, pathologically confirmed de novo DLBCL, or DLBCL transformed from previously diagnosed indolent lymphoma (e.g., follicular lymphoma) 6. Patients must have received at least 2 but no more than 5 previous systemic regimens for the treatment of their de novo or transformed DLBCL including (i) at least one course of anthracycline-based chemotherapy (unless absolutely contraindicated due to cardiac dysfunction, in which case other active agents such as etoposide, bendamustine or gemcitabine must have been given) and (ii) at least one course of anti-CD20 immunotherapy (e.g., rituximab), unless contraindicated due to severe toxicity. Patients who were considered ineligible for standard multi-agent immunochemotherapy must have received at least two and no more than five prior treatment regimens including at least one course of anti-CD20 antibodies and must be approved by the Medical Monitor. Prior stem cell transplantation is allowed; induction, consolidation, stem cell collection, preparative regimen and transplantation ± maintenance are considered a single line of therapy. 7. For patients whose most recent systemic anti-DLBCL therapy induced a PR or CR, at least 60 days must have elapsed since the end of that therapy. For all other patients, at least 14 weeks (98 days) must have elapsed since the end of their most recent systemic anti DLBCL therapy. Palliative localized radiation within the therapy-free interval is allowed. Non chemotherapy maintenance will not be considered anti DLBCL therapy, and therefore is allowed during the therapy-free interval . 8. Documented clinical or radiographic evidence of progressive DLBCL prior to dosing. 9. Patients must have measurable disease per the revised criteria for response assessment of lymphoma (Cheson, 2014). Lymph nodes should be considered abnormal if the long axis is > 1.5 cm, regardless of the short axis. If a lymph node has a long axis of 1.1 to 1.5 cm, it should only be considered abnormal if its short axis is > 1.0. Lymph nodes = 1.0 by = 1.0 will not be considered abnormal for relapse or PD. 10. Female patients of child-bearing potential must have a negative serum pregnancy test at screening and agree to use reliable methods of contraception for three months after their last dose of medication. Male patients must use a reliable method of contraception if sexually active with a female of child-bearing potential.. For both male and female patients, effective methods of contraception must be used throughout the study and for three months following the last dose (see Section 13.5.2.1 Permitted Concomitant Medication – Prevention of Pregnancy for description of acceptable contraceptive methods). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 159 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 161
Exclusion criteria
Exclusion criteria: Patients meeting any of the following exclusion criteria are not eligible to enroll in this study. 1. Patients who are pregnant or lactating 2. DLBCL with mucosa-associated lymphoid tissue [MALT] lymphoma, composite lymphoma (HL+NHL), or DLBCL transformed from diseases other than indolent NHL 3. Primary mediastinal (thymic) large B-cell lymphoma (PMBL) 4. Patients must not be eligible for high-dose chemotherapy with autologous stem cell transplantation rescue (investigator must provide detailed documentation for ineligibility) 5. Known central nervous system (CNS) lymphoma or meningeal involvement 6. For patients whose most recent systemic anti-DLBCL therapy induced a PR or CR: Radiation, chemotherapy, immunotherapy, radio-immunotherapy, or any other anticancer therapy other than glucocorticoids 50,000/ul c) Hepatic dysfunction: bilirubin >2.0 times the upper limit of normal (ULN) (except patients with Gilbert’s syndrome: total bilirubin of > 3 x ULN) and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) >2.5 times ULN. In patients with known liver involvement of their DLBCL, AST and ALT >5 x ULN. d) Severe renal dysfunction: estimated creatinine clearance of < 30 mL/min, measured in 24 hour urine or calculated using the formula of Cockroft and Gault [(140-Age) • Mass (kg)/(72 • creatinine mg/dL); multiply by 0.85 if female] e) Hematopoietic dysfunction: hemoglobin < 10.0 g/dL within 14
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of selinexor 60 mg in comparison to a minimally effective lower threshold level of ORR of 15% in patients with R/R DLBCL.;Secondary Objective: • To determine DOR • To determine the disease control rate (DCR) • To assess the safety profile of selinexor ;Primary end point(s): Objective disease response assessment will be made according to the revised criteria for response assessment of lymphoma (Cheson, 2014). The data used for primary statistical analysis will be provided by the central imaging laboratory. The primary endpoint of ORR will be assessed as the ORR of selinexor 60 mg compared to a minimally effective lower threshold level of ORR of 15%. • The ORR is defined as the proportion of patients who achieve either CR or PR. • Progression is defined as the first occurrence of PD per the revised response criteria. Clinical disease progression in the absence of formal criteria for PD should be radiographically confirmed whenever possible and must be comprehensively documented by the treating physician. Patients who have clinical disease progression in the absence of formal criteria for PD or radiographical confirmation will be censored at the time of last non-PD adequate response assessment. • DOR is defined as the duration of time from first occurrence of CR or PR until the first date that disease progression is objectively documented • DCR is defined as the proportion of patients who achieve CR, PR, or SD for a minimum of 4 weeks, following randomization/enrollment (i.e., ORR + SD) • PFS is defined as the duration of time from randomization/enrollment until progression or death due to any cause. A sensitivity analysis will also be performed for PFS where death will be included if it may be reasonably attributed to the patient’s underlying DLBCL. • OS is defined as the duration of time from randomization/enrollment until death due to any cause. A sensitivity analysis will also be performed for OS where death will b | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Efficacy Endpoints • DOR, defined as the duration of time from first occurrence of CR or PR until the first date that disease progression is objectively documented. • DCR, defined as the proportion of patients who achieve CR, PR, or SD for a minimum of 4 weeks, following randomization/enrollment (i.e., ORR + SD). Secondary Safety Endpoints • Safety endpoints include AE reports, Eastern Cooperative Oncology Group (ECOG) performance status, vital signs, physical examinations, electrocardiograms (ECGs), ophthalmic examinations, concomitant medications and laboratory safety evaluations.;Timepoint(s) of evaluation of this end point: End of study | — |
Countries
Austria, Belgium, Bulgaria, Canada, France, Germany, Greece, Hungary, Israel, Italy, Netherlands, Poland, Serbia, Spain, United Kingdom, United States
Contacts
Public ContactClinical Trial Information Desk
Karyopharm Therapeutics, Inc.
Outcome results
None listed