Efficacy and Safety Study of Selinexor in Relapsed or Refractory Peripheral T-cell Lymphoma or Cutaneous T-cell Lymphoma

Study Overview
=================
Brief Summary
-----------------
This is a single-arm, multi-center, open-label phase 2 study of the SINE™ compound selinexor given orally to patients with relapsed or refractory PTCL or CTCL. Approximately 60 patients with relapsed or refractory PTCL or CTCL who meet the eligibility criteria and have none of the exclusion criteria will be enrolled to receive selinexor until either disease progression or intolerance has occurred.

Detailed Description
-----------------
This is a single-arm, multi-center, open-label phase 2 study of the SINE™ compound selinexor given orally to patients with relapsed or refractory PTCL or CTCL. Approximately 60 patients with relapsed or refractory PTCL or CTCL who meet the eligibility criteria and have none of the exclusion criteria will be enrolled to receive selinexor until either disease progression or intolerance has occurred. Enrolled patients will be given selinexor as an oral fixed 60 mg dose (equivalent to  35 mg/m²) on Days 1 and 3 of Weeks 1-4 of each 4-week cycle (total 8 doses per cycle). There is no maximum treatment duration. Patients will receive supportive therapy to mitigate selinexor side effects, as well as best supportive care (BSC). Patients enrolled under Protocol Versions <3.0 were to receive selinexor orally, at a fixed dose of 60 mg (equivalent to  35 mg/m²) on Days 1 and 3 of Weeks 1-3 of each 4-week cycle (total of 6 doses per cycle). Selinexor was not taken during Week 4. For all patients enrolled in this study (regardless of the protocol version) who continued onto Cycle 3 and forward, the dose was to be increased by 20 mg to 80 mg (administered on Days 1 and 3 of Weeks 1-4), only after consultation with the Sponsor's Medical Monitor.

Official Title
-----------------
Multi-center, Phase 2, Open-label Study of Efficacy and Safety of the Selective Inhibitor of Nuclear Export (SINE™) Selinexor (KPT-330) in Patients With Relapsed or Refractory Peripheral T-cell Lymphoma (PTCL) and Cutaneous T-cell Lymphoma (CTCL)

Conditions
-----------------
Peripheral T-cell Lymphoma (PTCL), Cutaneous T-cell Lymphoma (CTCL)

Intervention / Treatment
-----------------
* Drug: Selinexor


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: ECOG performance status of ≤2. Relapsed or refractory disease to at least one prior systemic regimen. Measurable disease: according to International Working Group (IWG) guidelines for all patients with PTCL and according to CTCL Response in Skin consensus criteria for all patients with CTCL. Objective, documented evidence of disease progression on study entry. Exclusion Criteria: Known active central nervous system (CNS) lymphoma. Active graft-versus-host disease after allogeneic stem cell transplantation. At least 4 months must have elapsed since completion of allogeneic stem cell transplantation. Unable to swallow tablets or malabsorption syndrome, disease significantly affecting gastrointestinal function.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Selinexor<br>60 mg dose (equivalent to  35 mg/m²) | Drug: Selinexor<br>* 20 mg oral tablets: 60 mg dose on Days 1 and 3 of Weeks 1-4 of each 4-week cycle (Protocol V.3.0). 20 mg oral tablets: 60 mg dose on Days 1 and 3 of Weeks 1-3 of each 4-week cycle (Protocol V.<3.0). Number of Cycles: up to 12 but there is no maximal duration for treatment.<br>* Other names: KPT-330;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | Overall Response (OR) = Complete Response (CR) + Partial Response (PR). Objective disease response assessment in PTCL patients was made according to the revised response criteria based on the International Working Group (IWG) guidelines for malignant lymphoma (Cheson, 2007). Objective disease response assessment in CTCL patients was assessed according to the revised CTCL Consensus Response Criteria (Olsen, 2011) using physical examination, including the Modified Severity Weighted Assessment Tool (mSWAT) for skin assessment. CTCL Global Response Score was used as a secondary efficacy assessment. Progression was defined as the first occurrence of progressive disease (PD) per the revised response criteria. Clinical disease progression in the absence of formal criteria for PD must be documented by a physician. | Disease response was assessed at screening and every 8 weeks (patients with PTCL); or at Cycle 1 Day 1 and every 4 weeks (patients with CTCL), until disease progression. | 
| Best Overall Response: Complete Response (CR) | Patients who achieved CR (disappearance of all detectable evidence of disease). Objective disease response assessment in PTCL patients was made according to the revised response criteria based on the International Working Group (IWG) guidelines for malignant lymphoma (Cheson, 2007). Objective disease response assessment in CTCL patients was assessed according to the revised CTCL Consensus Response Criteria (Olsen, 2011) using physical examination, including the Modified Severity Weighted Assessment Tool (mSWAT) for skin assessment. CTCL Global Response Score was used as a secondary efficacy assessment. | Disease response was assessed at screening and every 8 weeks (patients with PTCL); or at Cycle 1 Day 1 and every 4 weeks (patients with CTCL), until disease progression. | 
| Best Overall Response: Partial Response (PR) | Patients whose best overall response to study treatment was PR (regression of measurable disease and no new sites). Objective disease response assessment in PTCL patients was made according to the revised response criteria based on the International Working Group (IWG) guidelines for malignant lymphoma (Cheson, 2007). Objective disease response assessment in CTCL patients was assessed according to the revised CTCL Consensus Response Criteria (Olsen, 2011) using physical examination, including the Modified Severity Weighted Assessment Tool (mSWAT) for skin assessment. CTCL Global Response Score was used as a secondary efficacy assessment. | Disease response was assessed at screening and every 8 weeks (patients with PTCL); or at Cycle 1 Day 1 and every 4 weeks (patients with CTCL), until disease progression. | 
| Best Overall Response: Stable Disease (SD) | Patients whose best overall response to study treatment was SD (failure to attain criteria needed for CR or PR, or to meet criteria for PD). Objective disease response assessment in PTCL patients was made according to the revised response criteria based on the International Working Group (IWG) guidelines for malignant lymphoma (Cheson, 2007). Objective disease response assessment in CTCL patients was assessed according to the revised CTCL Consensus Response Criteria (Olsen, 2011) using physical examination, including the Modified Severity Weighted Assessment Tool (mSWAT) for skin assessment. CTCL Global Response Score was used as a secondary efficacy assessment. | Disease response was assessed at screening and every 8 weeks (patients with PTCL); or at Cycle 1 Day 1 and every 4 weeks (patients with CTCL), until disease progression. | 
| Best Overall Response: Progressive Disease (PD) | Patients whose best overall response to study treatment was PD. Progression was defined as the first occurrence of progressive disease (PD). Objective disease response assessment in PTCL patients was made according to the revised response criteria based on the International Working Group (IWG) guidelines for malignant lymphoma (Cheson, 2007). Objective disease response assessment in CTCL patients was assessed according to the revised CTCL Consensus Response Criteria (Olsen, 2011) using physical examination, including the Modified Severity Weighted Assessment Tool (mSWAT) for skin assessment. CTCL Global Response Score was used as a secondary efficacy assessment. Clinical disease progression in the absence of formal criteria for PD must be documented by a physician. | Disease response was assessed at screening and every 8 weeks (patients with PTCL); or at Cycle 1 Day 1 and every 4 weeks (patients with CTCL), until disease progression. | 
| Best Overall Response: Not Evaluable (NE) | Patients who could not be assessed quantitatively for disease response for any reason. | Disease response was assessed at screening and every 8 weeks (patients with PTCL); or at Cycle 1 Day 1 and every 4 weeks (patients with CTCL), until disease progression. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Stable Disease, Including Patients With Partial Response | Duration of time from the date of start of study treatment to the date of disease progression. Objective disease response assessment in PTCL patients was made according to the revised response criteria based on the International Working Group (IWG) guidelines for malignant lymphoma (Cheson, 2007). Objective disease response assessment in CTCL patients was assessed according to the revised CTCL Consensus Response Criteria (Olsen, 2011) using physical examination, including the Modified Severity Weighted Assessment Tool (mSWAT) for skin assessment. CTCL Global Response Score was used as a secondary efficacy assessment. | Date of start of study treatment to date of progression. Patients without documented PD are censored on date of last radiologic assessment. | 
| Disease Control Rate (DCR) | Percentage of patients who have CR, PR, or SD lasting ≥ 8 weeks. Objective disease response assessment in PTCL patients was made according to the revised response criteria based on the International Working Group (IWG) guidelines for malignant lymphoma (Cheson, 2007). Objective disease response assessment in CTCL patients was assessed according to the revised CTCL Consensus Response Criteria (Olsen, 2011) using physical examination, including the Modified Severity Weighted Assessment Tool (mSWAT) for skin assessment. CTCL Global Response Score was used as a secondary efficacy assessment. | Disease response was assessed at screening and every 8 weeks (patients with PTCL); or at Cycle 1 Day 1 and every 4 weeks (patients with CTCL), until disease progression. | 
| Progression Free Survival (PFS) | Duration of time from start of study treatment to date of disease progression or death from any cause. | Study treatment start date to date of disease progression or date of death. Patients without documented PD are censored on date of last radiologic assessment. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
PTCL, CTCL, Peripheral T-cell Lymphoma, Cutaneous T-cell Lymphoma, Karyopharm, KPT-330, Selinexor