Selinexor in Initial or Refractory and/or Relapsed Richter's Transformation
Condition: Richter's Transformation
Intervention: selinexor
Intervention description: 60 mg dose twice weekly, on Days 1 and 3 of weeks 1-4 of each 4-week cycle; dose may be increased to 80 mg after Cycle 1 unless clinically contraindicated (Protocol V.5.0).
60 mg dose twice weekly on Days 1 and 3 of weeks 1-3 of each 4-week cycle; dose may be increased to 80 mg at Cycle 3 Day 1 unless clinically contraindicated (Protocol V.4.0).
60 mg/m² dose, based on BSA, twice weekly, on Days 1 and 3 of weeks 1-3 of each 4-week cycle (Protocol V. 3.0).
60 mg/m² dose, based on BSA, twice weekly, on Days 1 and 3 of weeks 1-4 of each 4-week cycle (Protocol V. < 3.0).
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 27.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Richter's Transformation; Richter's Syndrome; Karyopharm; selinexor; KPT-330; SIRRT; CLL

Summary:

      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.
    

Eligibility criteria:

        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).