Selinexor in Initial or Refractory and/or Relapsed Richter's Transformation
Selinexor in Initial or Refractory and/or Relapsed Richter's Transformation
This is a multi-center, phase 2, single arm, open-label study of oral selinexor monotherapy
 in patients with Richter's Transformation, arising in the setting of prior chronic
 lymphocytic leukemia (CLL), after at least one chemo-immunotherapy regimen for CLL.
Multi-center, phase 2, single arm, open-label study of oral selinexor monotherapy in patients
 with Richter's Transformation, arising in the setting of prior CLL, documented by
 histologically confirmed lymphoma, including diffuse large B-cell (DLBCL) and immunoblastic
 variants. Eligible patients must have had at least one prior regimen for CLL. Approximately
 50 patients are anticipated to be treated in this study. Eligible patients following
 screening will receive selinexor orally twice weekly at a dose of 60 mg. The selinexor dose
 may be increased to 80 mg after Cycle 1 unless clinically contraindicated. Patients may
 continue in multiple treatment cycles at a given dose; there is no maximum treatment
 duration. Each cycle is 28 days. Dose adjustments will be made as appropriate by the
 investigator.

 Patients who were treated twice weekly for weeks 1-3 under a previous version of the protocol
 may, at the discretion of the investigator, have had the frequency of selinexor dosing
 increased to twice weekly for weeks 1-4. If there was no contraindicated toxicity, the
 selinexor dose may have been increased to 80 mg at Cycle 3.
Inclusion Criteria:

 -  Richter's Transformation, arising in the setting of prior CLL, documented by
 histologically confirmed lymphoma, including large B-cell and immunoblastic variants.

 -  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).

 -  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.

 -  Objective documented evidence of disease progression at study entry

 -  Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 2

 Exclusion Criteria:

 -  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.

 -  Prolymphocytic transformation

 -  Less than 1 month since completion of autologous stem cell transplantation or less
 than 3 months since completion of allogeneic stem cell transplantation

 -  Major surgery within 4 weeks of C1D1

 -  Impairment of GI function or GI disease that could interfere with the absorption of
 selinexor, including obstructed GI tract and uncontrolled vomiting or diarrhea.

 -  Inability or unwillingness to take supportive medications including a centrally acting
 appetite stimulant (e.g., mirtazapine or olanzapine) and a peripherally acting
 appetite stimulant (e.g., low dose glucocorticoids or megesterol acetate).