Clinical trial NCT02138786: 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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Richter's Transformation
Keywords: Richter's Transformation
Richter's Syndrome
Karyopharm
selinexor
KPT-330
SIRRT
CLL
Lead sponsor: Karyopharm Therapeutics Inc
Sponsor class: INDUSTRY
First posted: 2014-05-15
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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).

Primary outcomes:
measure: Percentage of Participants With Overall Response (Overall Response Rate)
timeFrame: 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.
measure: Number of Participants With Complete Response (CR)
timeFrame: 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.
measure: Number of Participants With Partial Response (PR)
timeFrame: 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.
measure: Number of Participants With Stable Disease (SD)
timeFrame: 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.
measure: Number of Participants With Progressive Disease (PD)
timeFrame: 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.
measure: Number of Participants With Not Evaluable (NE) Response
timeFrame: 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:
measure: Percentage of Participants With Disease Control (Disease Control Rate)
timeFrame: 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.
measure: Duration of Progression Free Survival (PFS)
timeFrame: 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.
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona Cancer Center
state: Arizona
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Santa Monica
country: United States
facility: University of California-Los Angeles
state: California
city: Atlanta
country: United States
facility: Winship Cancer Institute / Emory University
state: Georgia
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute/University of Utah
state: Utah
city: Ulm
country: Germany
facility: University of Ulm
state: Baden-Württemberg
city: Koeln
country: Germany
facility: University Hospital of Cologne
city: Kraków
country: Poland
facility: Malopolskie Centrum Medyczne
city: Lodz
country: Poland
facility: Copernicus Memorial Hospital, Department of Hematology
city: Warszawa
country: Poland
facility: Maria Skłodowska-Curie Institue of Oncology
city: Pamplona
country: Spain
facility: Instituto Clinico Navarra, Pamplona
state: Navarra
city: Barcelona
country: Spain
facility: Institut Català d'Oncologia Av.
city: Barcelona
country: Spain
facility: Hospital Vall Hebron
city: Sutton
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
state: Surrey
city: Oxford
country: United Kingdom
facility: Churchill Hospital: Cancer and Haematology Centre
Study officials:
References:
citation: 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.