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

NCT02138786 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: KCP-330-010
• Study Type: interventional
• Target: 27
• Locations: 5 countries
• Sites: 17

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.

Conditions

Richter's Transformation

Keywords

Richter's Transformation; Richter's Syndrome; Karyopharm; selinexor; KPT-330; SIRRT; CLL

Outcome Measures

Primary Outcomes (6)

• Percentage of Participants With Overall Response (Overall Response Rate)

  Overall Response Rate (ORR) is defined as the point estimate of the percentage of patients who have complete response (CR) or partial response (PR). Disease response was assessed using the International Working Group (IWG) Response Criteria for non-Hodgkin's lymphoma (Cheson 2007), including assessment of lymph node, spleen and liver lesions by PET (positron emission tomography) scan and assessment of bone marrow biopsies by morphologic, immunohistochemistry, and flow cytometry tests. CR was defined as disappearance of all evidence of disease, and PR was defined as ≥ 50% regression of measurable disease and no new sites.

  Assessments were performed at Screening or Cycle 1/Day 1 prior to dosing and on Cycle 3/Day 1 and alternate cycles thereafter until disease progression, study drug intolerability had been reached, study withdrawal, or death.

• Number of Participants With Complete Response (CR)

  Number of patients who achieved CR (complete disappearance of all detectable evidence of disease). Disease response was assessed using the International Working Group (IWG) Response Criteria for non-Hodgkin's lymphoma (Cheson 2007), including assessment of lymph node, spleen and liver lesions by PET (positron emission tomography) scan and assessment of bone marrow biopsies by morphologic, immunohistochemistry, and flow cytometry tests.

  Assessments were performed at Screening or Cycle 1/Day 1 prior to dosing and on Cycle 3/Day 1 and alternate cycles thereafter until disease progression, study drug intolerability had been reached, study withdrawal, or death.

• Number of Participants With Partial Response (PR)

  Number of patients whose best overall response to study treatment was PR (≥ 50% regression of measurable disease and no new sites). Disease response was assessed using the International Working Group (IWG) Response Criteria for non-Hodgkin's lymphoma (Cheson 2007), including assessment of lymph node, spleen and liver lesions by PET (positron emission tomography) scan and assessment of bone marrow biopsies by morphologic, immunohistochemistry, and flow cytometry tests.

  Assessments were performed at Screening or Cycle 1/Day 1 prior to dosing and on Cycle 3/Day 1 and alternate cycles thereafter until disease progression, study drug intolerability had been reached, study withdrawal, or death.

• Number of Participants With Stable Disease (SD)

  Number of patients whose best overall response to study treatment was SD (failure to attain criteria for CR or PR, or to meet criteria for PD). Disease response was assessed using the International Working Group (IWG) Response Criteria for non-Hodgkin's lymphoma (Cheson 2007), including assessment of lymph node, spleen and liver lesions by PET (positron emission tomography) scan and assessment of bone marrow biopsies by morphologic, immunohistochemistry, and flow cytometry tests.

  Assessments were performed at Screening or Cycle 1/Day 1 prior to dosing and on Cycle 3/Day 1 and alternate cycles thereafter until disease progression, study drug intolerability had been reached, study withdrawal, or death.

• Number of Participants With Progressive Disease (PD)

  Number of patients whose best overall response to study treatment was PD (any new lesion or increase by ≥ 50% of previously involved sites from nadir). Disease response was assessed using the International Working Group (IWG) Response Criteria for non-Hodgkin's lymphoma (Cheson 2007), including assessment of lymph node, spleen and liver lesions by PET (positron emission tomography) scan and assessment of bone marrow biopsies by morphologic, immunohistochemistry, and flow cytometry tests.

  Assessments were performed at Screening or Cycle 1/Day 1 prior to dosing and on Cycle 3/Day 1 and alternate cycles thereafter until disease progression, study drug intolerability had been reached, study withdrawal, or death.

• Number of Participants With Not Evaluable (NE) Response

  Number of patients who could not be assessed quantitatively for disease response for any reason.

  Assessments were performed at Screening or Cycle 1/Day 1 prior to dosing and on Cycle 3/Day 1 and alternate cycles thereafter until disease progression, study drug intolerability had been reached, study withdrawal, or death.

Secondary Outcomes (2)

• Percentage of Participants With Disease Control (Disease Control Rate)

  Assessments were performed at Screening or Cycle 1/Day 1 prior to dosing and on Cycle 3/Day 1 and alternate cycles thereafter until disease progression, study drug intolerability had been reached, study withdrawal, or death.

• Duration of Progression Free Survival (PFS)

  Assessments were performed at Screening or Cycle 1/Day 1 prior to dosing and on Cycle 3/Day 1 and alternate cycles thereafter until disease progression, study drug intolerability had been reached, study withdrawal, or death.

Study Arms (1)

selinexor

EXPERIMENTAL

oral tablets * 10 mg \& 25 mg (bottled); or * 20 mg (blister pack)

Drug: selinexor

Interventions

selinexor DRUG

* 60 mg dose twice weekly, on Days 1 and 3 of weeks 1-4 of each 4-week cycle; dose may be increased to 80 mg after Cycle 1 unless clinically contraindicated (Protocol V.5.0). * 60 mg dose twice weekly on Days 1 and 3 of weeks 1-3 of each 4-week cycle; dose may be increased to 80 mg at Cycle 3 Day 1 unless clinically contraindicated (Protocol V.4.0). * 60 mg/m² dose, based on BSA, twice weekly, on Days 1 and 3 of weeks 1-3 of each 4-week cycle (Protocol V. 3.0). * 60 mg/m² dose, based on BSA, twice weekly, on Days 1 and 3 of weeks 1-4 of each 4-week cycle (Protocol V. \< 3.0).

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:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Karyopharm Therapeutics Inc: lead

Study Sites (17)

University of Arizona Cancer Center

Tucson, Arizona, 85724, United States

Location

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

University of California-Los Angeles

Santa Monica, California, 90404, United States

Location

Winship Cancer Institute / Emory University

Atlanta, Georgia, 30322, United States

Location

Weill Cornell Medical College

New York, New York, 10065, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43202, United States

Location

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112, United States

Location

University of Ulm

Ulm, Baden-Wurttemberg, 89081, Germany

Location

University Hospital of Cologne

Cologne, 50937, Germany

Location

Malopolskie Centrum Medyczne

Krakow, 30-510, Poland

Location

Copernicus Memorial Hospital, Department of Hematology

Lodz, 93-513, Poland

Location

Maria Skłodowska-Curie Institue of Oncology

Warsaw, 02-034, Poland

Location

Instituto Clinico Navarra, Pamplona

Pamplona, Navarre, 31008, Spain

Location

Institut Català d'Oncologia Av.

Barcelona, 08010, Spain

Location

Hospital Vall Hebron

Barcelona, 08035, Spain

Location

The Royal Marsden NHS Foundation Trust

Sutton, Surrey, SM2 5PT, United Kingdom

Location

Churchill Hospital: Cancer and Haematology Centre

Oxford, OX3 8JL, United Kingdom

Location

Related Publications (1)

• Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, Coiffier B, Fisher RI, Hagenbeek A, Zucca E, Rosen ST, Stroobants S, Lister TA, Hoppe RT, Dreyling M, Tobinai K, Vose JM, Connors JM, Federico M, Diehl V; International Harmonization Project on Lymphoma. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007 Feb 10;25(5):579-86. doi: 10.1200/JCO.2006.09.2403. Epub 2007 Jan 22.

  PMID: 17242396 BACKGROUND

MeSH Terms

Interventions

selinexor

Limitations and Caveats

The low number of formal objective responses (leading to the termination of the study following the first stage), coupled with the high number of censored observations, limited meaningful analyses and the ability to draw conclusions from the data.

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: May 13, 2014
• First Posted: May 15, 2014
• Study Start: November 14, 2014
• Primary Completion: August 31, 2016
• Study Completion: August 31, 2016
• Last Updated: January 26, 2023
• Results First Posted: February 11, 2020

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will share

Locations

DE (2); GB (2); ES (3); US (7); PL (3)