Selinexor in Initial or Refractory and/or Relapsed Richter’s Transformation

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Richter syndrome
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Brief Title

Selinexor in Initial or Refractory and/or Relapsed Richter's Transformation

Official Title

A Phase 2 Study of the Safety and Anti-tumor Activity of the Oral Selective Inhibitor of Nuclear Export (SINE) Selinexor (KPT-330) in Patients With Initial or Refractory and/or Relapsed Richter's Transformation (RT)

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.

Study Phase

Phase 2

Study Type

Interventional

Primary Outcome

Percentage of Participants With Overall Response (Overall Response Rate)

Secondary Outcome

 Percentage of Participants With Disease Control (Disease Control Rate)

Condition

Richter's Transformation

Intervention

selinexor

Study Arms / Comparison Groups

 selinexor
Description:  oral tablets
10 mg & 25 mg (bottled); or
20 mg (blister pack)

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status

Drug

Estimated Enrollment

27

Start Date

November 14, 2014

Completion Date

August 31, 2016

Primary Completion Date

August 31, 2016

Eligibility Criteria

        Inclusion Criteria:

          -  Richter's Transformation, arising in the setting of prior CLL, documented by
             histologically confirmed lymphoma, including large B-cell and immunoblastic variants.

          -  All patients must have received at least one prior regimen for CLL, including
             cytotoxic chemotherapy, anti-CD20 monoclonal antibodies, a BTK inhibitor, or a PI3K
             inhibitor. Patients may have received high dose chemotherapy/autologous stem cell
             transplant (HDT/ASCT) or allogeneic hematopoietic stem cell transplant (allo SCT).

          -  One or more measurable (> 1.5 cm in longest dimension) disease sites on CT (preferably
             PET/CT) or, if CT is contraindicated, MRI (preferably PET/MRI) scans.

          -  Objective documented evidence of disease progression at study entry

          -  Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 2

        Exclusion Criteria:

          -  Radiation, chemotherapy, or immunotherapy or any other anticancer therapy ≤ 2 weeks
             prior to Cycle 1 Day 1, except ibrutinib which may be continued until one day prior to
             initiation of selinexor; radio-immunotherapy 4 weeks prior to Cycle 1 Day 1. Patients
             must have recovered to Grade ≤ 1 from clinically significant adverse effects.

          -  Prolymphocytic transformation

          -  Less than 1 month since completion of autologous stem cell transplantation or less
             than 3 months since completion of allogeneic stem cell transplantation

          -  Major surgery within 4 weeks of C1D1

          -  Impairment of GI function or GI disease that could interfere with the absorption of
             selinexor, including obstructed GI tract and uncontrolled vomiting or diarrhea.

          -  Inability or unwillingness to take supportive medications including a centrally acting
             appetite stimulant (e.g., mirtazapine or olanzapine) and a peripherally acting
             appetite stimulant (e.g., low dose glucocorticoids or megesterol acetate).

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Michael Kauffman, MD, PhD, ,

Location Countries

Germany

Location Countries

Germany

Administrative Informations

NCT ID

NCT02138786

Organization ID

KCP-330-010

Responsible Party

Sponsor

Study Sponsor

Karyopharm Therapeutics Inc

Study Sponsor

Michael Kauffman, MD, PhD, Study Director, Karyopharm Therapeutics Inc

Verification Date

September 2020