Selinexor in Initial or Refractory and/or Relapsed Richter's Transformation

- 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

- 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).