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

NCT02314247 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: KCP-330-013
• Study Type: interventional
• Target: 16
• Locations: 2 countries
• Sites: 5

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.

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (3)

• 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.

• 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.

• 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.

Study Arms (1)

Selinexor

EXPERIMENTAL

60 mg dose (equivalent to \~35 mg/m²)

Drug: Selinexor

Interventions

Selinexor DRUG

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.

Also known as: KPT-330

Selinexor

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Karyopharm Therapeutics Inc: lead

Study Sites (5)

Concord Repatriation General Hospital (CRGH)

Concord, New South Wales, 2139, Australia

Location

Royal North Shore Hospital

St Leonards, New South Wales, 2139, Australia

Location

Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

Cabrini Hospital

Malvern, Victoria, Australia

Location

National Cancer Centre

Singapore, 169610, Singapore

Location

MeSH Terms

Conditions

Lymphoma, T-Cell, Peripheral; Lymphoma, T-Cell, Cutaneous

Interventions

selinexor

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Limitations and Caveats

Due to unexpectedly slow recruitment, the Sponsor decided to terminate the study after 16 patients had been enrolled. The small study population limits the evaluation of both efficacy and safety of selinexor in patients with PTCL or CTCL.

Results Point of Contact

• Title: Jatin Shah, MD
• Organization: Karyopharm Therapeutics Inc.

jshah@karyopharm.com

(617) 658-0600

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2014
• First Posted: December 11, 2014
• Study Start: February 1, 2015
• Primary Completion: January 1, 2016
• Study Completion: February 1, 2016
• Last Updated: January 26, 2023
• Results First Posted: August 20, 2018

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will share

Locations

AU (4); SG (1)