Initial and Refractory/Relapsed Richters Transformation (RT) MedDRA version: 18.0 Level: PT Classification code 10058728 Term: Richter's syndrome System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Selinexor
Product Code: KPT-330
Pharmaceutical Form: Coated tablet
INN or Proposed INN: Selinexor
CAS Number: 1393477-72-9
Current Sponsor code: KPT-330
Concentration unit: mg milligram(
Sponsors
Karyopharm Therapeutics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Ability to understand and the willingness to sign a written informed consent document. 2. Richter’s transformation, arising in the setting of prior CLL, documented by histologically confirmed lymphoma, including large B-cell and immunoblastic variants. 3. All patients must have received at least one prior regimen for CLL, including cytotoxic chemotherapy, anti-CD20 monoclonal antibodies, a BTK inhibitor, or a PI3K inhibitor. Patients may have received high dose chemotherapy/autologous stem cell transplant (HDT/ASCT) or allogeneic hematopoietic stem cell transplant (allo SCT). 4. One or more measurable (> 1.5 cm in longest dimension) disease sites on CT (preferably PET/CT) or, if CT is contraindicated, MRI (preferably PET/MRI) scans. 5. Objective documented evidence of disease progression at study entry. • For patients newly diagnosed with RT, this includes histologic evidence of transformation to RT (on Screening, patients must have radiographic evidence consistent with RT). • For patients previously diagnosed with RT who have progressed after at least one prior therapy for RT, this includes radiographic and/or definitive clinical evidence of clinical progression. 6. Eastern Cooperative Oncology Group (ECOG) performance status of = 2 (Oken 1982) 7. Baseline platelet count = 30,000/mm3 (allowing platelet transfusion and/or growth factors to reach this criteria) and absolute neutrophil count = 500/mm3 (growth factors are allowed). 8. Patients who are hepatitis B PCR negative who have a recent ( 45 years old and have not experienced menses for > 2 years may have ß Hcg pregnancy test waived. Female patients of child-bearing potential must agree to use dual methods of contraception if sexually active and have a negative serum pregnancy test at Screening. Male patients must agree to use an effective barrier method of contraception if sexually active with a female of child-bearing potential. Acceptable methods of contraception are condoms with contraceptive foam; oral, implantable or injectable contraceptives; contraceptive patch; intrauterine device; diaphragm with spermicidal gel; or a sexual partner who is surgically sterilized or post-menopausal. Total (true) abstinence (when this is in line with the preferred and usual lifestyle of the patient), is an acceptable method of contraception. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post ovulation methods) and withdrawal are not acceptable methods of contraception. For both male and female patients, effective methods of contraception must be used throughout the study and for
Exclusion criteria
Exclusion criteria: 1. Patients who are pregnant or lactating 2. Radiation, chemotherapy, or immunotherapy or any other anticancer therapy = 2 weeks prior to Cycle 1 Day 1, except ibrutinib which may be continued until one day prior to initiation of selinexor; radio-immunotherapy 4 weeks prior to Cycle 1 Day 1. Patients must have recovered to Grade = 1 from clinically significant adverse effects. 3. Prolymphocytic transformation 4. Less than 1 month since completion of autologous stem cell transplantation or less than 3 months since completion of allogeneic stem cell transplantation 5. Major surgery within four weeks of Cycle 1 Day 1 6. Unstable cardiovascular function: • symptomatic ischemia, or • uncontrolled clinically significant conduction abnormalities (i.e., ventricular tachycardia on antiarrhythmic agents are excluded and 1st degree atrioventricular block or asymptomatic left anterior fascicular block/right bundle branch block will not be excluded), or • congestive heart failure of NYHA Class = 3, or • myocardial infarction within 3 months 7. Uncontrolled systemic infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose. Systemic infections controlled on concurrent anti-microbial agents and anti-microbial prophylaxis per institutional guidelines are acceptable, even if parenteral. 8. Presence of central nervous system (CNS) leukemia or lymphoma. Patients with active CNS malignancy. Asymptomatic small lesions are not considered active. Treated lesions may be considered inactive if they are stable for at least 3 months. Patient with malignant cells in their cerebrospinal fluid (CSF) without CNS symptoms may be included. 9. Known active hepatitis B virus (HBV) or C virus (HCV) infection; or known to be positive for HCV ribonucleic acid (RNA); patients with stable human immunodeficiency virus (HIV) on anti-retroviral therapy are acceptable. Patients with surface antigen (HBsAg) or hepatitis B PCR positivity will be excluded. 10. Impairment of gastrointestinal (GI) function or GI disease that could interfere with the absorption of selinexor, including obstructed GI tract and uncontrolled vomiting or diarrhea. 11. Inability or unwillingness to take supportive medications such as anti-nausea and anti-anorexia agents as recommended by the NCCN Clinical Practice Guidelines® (Appendix 3 and Appendix 4). 12. Serious psychiatric or medical conditions that could interfere with treatment. 13. Participation in an investigational anti-cancer study within 2 weeks prior to Cycle 1 Day 1. 14. Concurrent therapy with approved or investigational anticancer therapeutic. 15. Body surface area (BSA) <1.3 m2.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the Overall Response Rate (ORR) including Partial Response (PR) and Complete Response (CR), as well as the Duration of Response (DOR).;Secondary Objective: - To determine the Disease Control Rate (DCR = CR + PR + SD), as well as duration of DCR. - To determine Progression Free Survival (PFS). - To compare PFS on selinexor versus the patients PFS(s) on prior therapy(s) for RT, if applicable. - To determine Overall Survival (OS) from diagnosis and from initiation of selinexor. - To further evaluate toxicity of selinexor in this patient population. - To assess Quality of Life using 1) FACT-Lym Questionnaire and 2) the EQ-5D-5L Health Questionnaire .;Primary end point(s): The primary endpoint is Overall Response Rate (ORR) (as defined by the IWG Criteria) achieved by RT patients treated with single-agent selinexor. Supportive data will be provided by the duration of ORR (DOR).;Timepoint(s) of evaluation of this end point: The primary endpoint is overall response rate (ORR) achieved on or after Day 1 of Cycle 3, or at any 2nd cycle thereafter, by RT patients who have been treated with at least one dose of single-agent selixenor. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints include the determination of the following: - DCR, including supportive data provided by duration of DCR - Progression Free Survival (PFS) - PFS on selinexor versus the patients PFS(s) on prior therapy(s) for RT, if applicable - Overall Survival (OS), including OS from diagnosis and from initiation of selinexor - Further evaluation of toxicity of selinexor in this patient population - Assessment of Quality of Life using 1) the FACT-Lym Questionnaire and 2) the EQ 5D-5L Health Questionnaire;Timepoint(s) of evaluation of this end point: Secondary end points will be evaluated at end of study. | — |
Countries
Germany, United Kingdom, United States
Contacts
Public ContactClinical Trial Information Desk
Karyopharm Therapeutics, Inc.
Outcome results
None listed