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

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ClinicalTrials.gov Identifier: NCT02314247
Recruitment Status : Terminated (Due to enrollment challenges)
First Posted : December 11, 2014
Results First Posted : August 20, 2018
Last Update Posted : August 20, 2018
Sponsor:
Information provided by (Responsible Party):
Karyopharm Therapeutics Inc

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.


Condition or disease Intervention/treatment Phase
Peripheral T-cell Lymphoma (PTCL) Cutaneous T-cell Lymphoma (CTCL) Drug: Selinexor Phase 2

Expanded Access : Karyopharm Therapeutics Inc has indicated that access to an investigational treatment associated with this study is available outside the clinical trial.  

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 16 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Study Start Date : February 2015
Actual Primary Completion Date : January 2016
Actual Study Completion Date : February 2016


Arm Intervention/treatment
Experimental: Selinexor
60 mg dose (equivalent to ~35 mg/m²)
Drug: Selinexor

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.

Other Name: KPT-330




Primary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: 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.

  2. Best Overall Response: Complete Response (CR) [ Time Frame: 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.

  3. Best Overall Response: Partial Response (PR) [ Time Frame: 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.

  4. Best Overall Response: Stable Disease (SD) [ Time Frame: 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.

  5. Best Overall Response: Progressive Disease (PD) [ Time Frame: 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.

  6. Best Overall Response: Not Evaluable (NE) [ Time Frame: 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.


Secondary Outcome Measures :
  1. Duration of Stable Disease, Including Patients With Partial Response [ Time Frame: 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.

  2. Disease Control Rate (DCR) [ Time Frame: 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.

  3. Progression Free Survival (PFS) [ Time Frame: 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02314247


Locations
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Australia, New South Wales
Concord Repatriation General Hospital (CRGH)
Concord, New South Wales, Australia, 2139
Royal North Shore Hospital
St. Leonards, New South Wales, Australia, 2139
Westmead Hospital
Westmead, New South Wales, Australia, 2145
Australia, Victoria
Cabrini Hospital
Malvern, Victoria, Australia
Singapore
National Cancer Centre
Singapore, Singapore, 169610
Sponsors and Collaborators
Karyopharm Therapeutics Inc
Investigators
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Study Director: Michael Kauffman, MD, PhD Karyopharm Therapeutics Inc

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Responsible Party: Karyopharm Therapeutics Inc
ClinicalTrials.gov Identifier: NCT02314247     History of Changes
Other Study ID Numbers: KCP-330-013
First Posted: December 11, 2014    Key Record Dates
Results First Posted: August 20, 2018
Last Update Posted: August 20, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Karyopharm Therapeutics Inc:
PTCL
CTCL
Peripheral T-cell Lymphoma
Cutaneous T-cell Lymphoma
Karyopharm
KPT-330
Selinexor

Additional relevant MeSH terms:
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Lymphoma
Lymphoma, T-Cell
Lymphoma, T-Cell, Peripheral
Lymphoma, T-Cell, Cutaneous
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin