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

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)

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02314247

Enrollment

Registered

2014-12-11

Start date

2015-02-28

Completion date

2016-02-29

Last updated

2023-01-26

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

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

Keywords

PTCL, CTCL, Peripheral T-cell Lymphoma, Cutaneous T-cell Lymphoma, Karyopharm, KPT-330, Selinexor

Brief summary

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.

Interventions

DRUGSelinexor

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.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Best Overall Response: Not Evaluable (NE)	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.	Patients who could not be assessed quantitatively for disease response for any reason.
Best Overall Response: Partial Response (PR)	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.	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.
Best Overall Response: Stable Disease (SD)	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.	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.
Best Overall Response: Progressive Disease (PD)	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.	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.
Overall Response Rate (ORR)	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.	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.
Best Overall Response: Complete Response (CR)	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.	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.

Secondary

Measure	Time frame	Description
Disease Control Rate (DCR)	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.	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.
Progression Free Survival (PFS)	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.	Duration of time from start of study treatment to date of disease progression or death from any cause.
Duration of Stable Disease, Including Patients With Partial Response	Date of start of study treatment to date of progression. Patients without documented PD are censored on date of last radiologic assessment.	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.

Countries

Australia, Singapore

Participant flow

Participants by arm

Arm	Count
Selinexor (PTCL) Assigned to 60 mg dose, 6 doses/cycle	9
Selinexor (CTCL) Assigned to 60 mg dose, 6 doses/cycle (6 patients); Assigned to 60 mg dose, 8 doses/cycle (1 patient)	7
Total	16

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Adverse Event	2	1	0
Overall Study	Progression of Disease	6	2	0
Overall Study	Withdrawal by Subject	1	3	1

Baseline characteristics

Characteristic	Selinexor (CTCL)	Total	Selinexor (PTCL)
Age, Continuous	74 years	69 years	65 years
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants	0 Participants	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants	15 Participants	8 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	1 Participants	2 Participants	1 Participants
Race (NIH/OMB) Black or African American	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	6 Participants	14 Participants	8 Participants
Sex: Female, Male Female	2 Participants	4 Participants	2 Participants
Sex: Female, Male Male	5 Participants	12 Participants	7 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	3 / 9	1 / 7
other Total, other adverse events	9 / 9	7 / 7
serious Total, serious adverse events	8 / 9	1 / 7

Outcome results

Primary

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.