NCT02138786: SIRRT

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

Terminated Phase 2 Results posted Last updated 26 January 2023

What this trial tests

Phase 2 trial testing selinexor in Richter's Transformation in 27 participants. Terminated before completion.

Timeline

14 November 2014

Primary endpoint
31 August 2016

31 August 2016

Quick facts

Lead sponsor	Karyopharm Therapeutics Inc
Phase	Phase 2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	27
Start date	14 November 2014
Primary completion	31 August 2016
Estimated completion	31 August 2016
Sites	17 locations across United Kingdom, Germany, Poland, United States, Spain

Drugs / interventions tested

• selinexor — full drug profile →

Conditions studied

• Richter's Transformation — all drugs for Richter's Transformation →

Sponsor

Karyopharm Therapeutics Inc — full company profile →

Who can join

18 and older, any sex, with Richter's Transformation. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants With Overall Response (Overall Response Rate) Primary · 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.

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 measurab

Group	Value	95% CI
Selinexor	4	0.1 – 20.4

Number of Participants With Complete Response (CR) Primary · 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 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.

Group	Value	95% CI
Selinexor	0

Number of Participants With Partial Response (PR) Primary · 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 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.

Group	Value	95% CI
Selinexor	1

Number of Participants With Stable Disease (SD) Primary · 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 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.

Group	Value	95% CI
Selinexor	6

Number of Participants With Progressive Disease (PD) Primary · 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 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.

Group	Value	95% CI
Selinexor	7

Number of Participants With Not Evaluable (NE) Response Primary · 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 patients who could not be assessed quantitatively for disease response for any reason.

Group	Value	95% CI
Selinexor	11

Percentage of Participants With Disease Control (Disease Control Rate) Secondary · 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.

Disease Control Rate (DCR) is defined as the percentage of patients who achieved CR, PR, or SD lasting for at least 8 weeks. CR was defined as disappearance of all evidence of disease. PR was defined as ≥ 50% regression of measurable disease and no new sites. SD was defined as 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

Group	Value	95% CI
Selinexor	28.0	12.1 – 49.4

Duration of Progression Free Survival (PFS) Secondary · 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 days calculated from date of start of study therapy to date of progression based on IWG criteria, or date of death if progression did not occur. Patients who dropped out prior to study end without evidence of disease progression were censored at the day they were last known to be alive. Patients without documented disease progression or recurrence were censored at the date of last disease assessment. 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

Group	Value	95% CI
Selinexor	38.0	22.0 – 86.0

Adverse events — posted to ClinicalTrials.gov

Time frame: Treatment-emergent AEs were collected from the first day of dosing (Cycle 1 Day 1) through the 30-day follow-up.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Selinexor 60 mg/m² (8 Doses/Cycle)

Serious: 3/3 (100%)

Deaths: 1/3

Selinexor 60 mg (6 Doses/Cycle)

Serious: 9/15 (60%)

Deaths: 8/15

Selinexor 60 mg (8 Doses/Cycle)

Serious: 5/8 (63%)

Deaths: 2/8

Serious adverse events (26 terms)

Reaction	System	Selinexor 60 mg/m² (8 Dose…	Selinexor 60 mg (6 Doses/C…	Selinexor 60 mg (8 Doses/C…
Sepsis	Infections and infestations	—	—	—
Pneumonia	Infections and infestations	—	—	—
Staphylococcal Infection	Infections and infestations	—	—	—
Asthenia	General disorders	—	—	—
Fatigue	General disorders	—	—	—
General Physical Health Deterioration	General disorders	—	—	—
Mucosal Inflammation	General disorders	—	—	—
Pyrexia	General disorders	—	—	—
Decreased Appetite	Metabolism and nutrition disorders	—	—	—
Dehydration	Metabolism and nutrition disorders	—	—	—
Food Intolerance	Metabolism and nutrition disorders	—	—	—
Hypercalcaemia	Metabolism and nutrition disorders	—	—	—
Cerebral Haemorrhage	Nervous system disorders	—	—	—
Haemorrhage Intracranial	Nervous system disorders	—	—	—
Neuropathy Peripheral	Nervous system disorders	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—
Respiratory Failure	Respiratory, thoracic and mediastinal disorders	—	—	—
Febrile Neutropenia	Blood and lymphatic system disorders	—	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—	—
Deep Vein Thrombosis	Vascular disorders	—	—	—
Embolism Arterial	Vascular disorders	—	—	—
Supraventricular Tachycardia	Cardiac disorders	—	—	—
Clostridium Test Positive	Investigations	—	—	—
Back Pain	Musculoskeletal and connective tissue disorders	—	—	—
Tumour Haemorrhage	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—

Other adverse events (137 terms — click to expand)

Reaction	System	Selinexor 60 mg/m² (8 Dose…	Selinexor 60 mg (6 Doses/C…	Selinexor 60 mg (8 Doses/C…
Nausea	Gastrointestinal disorders	—	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—
Pyrexia	General disorders	—	—	—
Diarrhea	Gastrointestinal disorders	—	—	—
Oedema Peripheral	General disorders	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—
Decreased Appetite	Metabolism and nutrition disorders	—	—	—
Fatigue	General disorders	—	—	—
Asthenia	General disorders	—	—	—
Hyponatraemia	Metabolism and nutrition disorders	—	—	—
Back Pain	Musculoskeletal and connective tissue disorders	—	—	—
Dizziness	Nervous system disorders	—	—	—
Neutropenia	Blood and lymphatic system disorders	—	—	—
Hypokalaemia	Metabolism and nutrition disorders	—	—	—
Headache	Nervous system disorders	—	—	—
Weight Decreased	Investigations	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—
Constipation	Gastrointestinal disorders	—	—	—
Abdominal Pain	Gastrointestinal disorders	—	—	—
Anal Incontinence	Gastrointestinal disorders	—	—	—
Dry Mouth	Gastrointestinal disorders	—	—	—
Leukopenia	Blood and lymphatic system disorders	—	—	—
Leukocytosis	Blood and lymphatic system disorders	—	—	—
Hypocalcaemia	Metabolism and nutrition disorders	—	—	—
Hypercalcaemia	Metabolism and nutrition disorders	—	—	—
Hypoalbuminaemia	Metabolism and nutrition disorders	—	—	—
Hypomagnesaemia	Metabolism and nutrition disorders	—	—	—
Oral Candidiasis	Infections and infestations	—	—	—
Oral Infection	Infections and infestations	—	—	—
Hypercreatinaemia	Musculoskeletal and connective tissue disorders	—	—	—
Pain In Extremity	Musculoskeletal and connective tissue disorders	—	—	—
Hypotension	Vascular disorders	—	—	—
Blood Alkaline Phosphatase Increased	Investigations	—	—	—
C-Reactive Protein Increased	Investigations	—	—	—
Gamma-Glutamyltransferase Increased	Investigations	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—
Urinary Incontinence	Renal and urinary disorders	—	—	—
Tumour Pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—
Hyperbilirubinaemia	Hepatobiliary disorders	—	—	—

Most-reported serious reactions: Sepsis, Pneumonia, Staphylococcal Infection, Asthenia, Fatigue, General Physical Health Deterioration, Mucosal Inflammation, Pyrexia.

Data from ClinicalTrials.gov NCT02138786 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Selective inhibitors of nuclear export (SINE)--a novel class of anti-cancer agents.
   Parikh K, Cang S, Sekhri A, Liu D. · · 2014 · cited 124× · PMID 25316614 · DOI 10.1186/s13045-014-0078-0
2. The past, present, and future of CRM1/XPO1 inhibitors.
   Wang AY, Liu H. · · 2019 · cited 85× · PMID 30976603 · DOI 10.21037/sci.2019.02.03
3. XPO1 in B cell hematological malignancies: from recurrent somatic mutations to targeted therapy.
   Camus V, Miloudi H, Taly A, Sola B, et al · · 2017 · cited 67× · PMID 28196522 · DOI 10.1186/s13045-017-0412-4
4. Biology and Treatment of Richter Transformation.
   Condoluci A, Rossi D. · · 2022 · cited 39× · PMID 35392219 · DOI 10.3389/fonc.2022.829983
5. Richter Syndrome.
   Condoluci A, Rossi D. · · 2021 · cited 20× · PMID 33580422 · DOI 10.1007/s11912-020-01001-x
6. Immunochemotherapy for Richter syndrome: current insights.
   Puła B, Salomon-Perzyński A, Prochorec-Sobieszek M, Jamroziak K. · · 2019 · cited 10× · PMID 30788335 · DOI 10.2147/itt.s167456
7. Richter Syndrome: From Molecular Pathogenesis to Druggable Targets.
   Mouhssine S, Gaidano G. · · 2022 · cited 8× · PMID 36230566 · DOI 10.3390/cancers14194644
8. Prognostic and functional role of the nuclear export receptor 1 (XPO1) in gastrointestinal cancers: a potential novel target?
   Sokolova V, Gruber R, Pammer LM, Kocher F, et al · · 2024 · cited 1× · PMID 39729162 · DOI 10.1007/s11033-024-10169-5