Conditions: Richter's Transformation
Keywords: Richter's Transformation Richter's Syndrome Karyopharm selinexor KPT-330 SIRRT CLL
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 27
Healthy volunteers: no

Brief 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.

Detailed description:
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.

Arms:
arm 1: oral tablets

* 10 mg \& 25 mg (bottled); or
* 20 mg (blister pack)

Interventions: intervention 1: selinexor
Intervention descriptions: intervention 1: * 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).

Protocol document: