SIRRT: Selinexor in Initial or Refractory and/or Relapsed Richter's Transformation
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: selinexor oral tablets 10 mg & 25 mg (bottled); or 20 mg (blister pack) |
Drug: selinexor
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).
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants With Overall Response (Overall Response 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.]
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.
- Number of Participants With Complete Response (CR) [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.
- Number of Participants With Partial Response (PR) [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.
- Number of Participants With Stable Disease (SD) [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.
- Number of Participants With Progressive Disease (PD) [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.
- Number of Participants With Not Evaluable (NE) Response [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.
Secondary Outcome Measures
- 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.]
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 of bone marrow biopsies by morphologic, immunohistochemistry, and flow cytometry tests.
- 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.]
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 lesions by PET (positron emission tomography) scan and assessment of bone marrow biopsies by morphologic, immunohistochemistry, and flow cytometry tests. .
Eligibility Criteria
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).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Arizona Cancer Center | Tucson | Arizona | United States | 85724 |
| 2 | City of Hope National Medical Center | Duarte | California | United States | 91010 |
| 3 | University of California-Los Angeles | Santa Monica | California | United States | 90404 |
| 4 | Winship Cancer Institute / Emory University | Atlanta | Georgia | United States | 30322 |
| 5 | Weill Cornell Medical College | New York | New York | United States | 10065 |
| 6 | Ohio State University Comprehensive Cancer Center | Columbus | Ohio | United States | 43202 |
| 7 | Huntsman Cancer Institute/University of Utah | Salt Lake City | Utah | United States | 84112 |
| 8 | University of Ulm | Ulm | Baden-Württemberg | Germany | 89081 |
| 9 | University Hospital of Cologne | Koeln | Germany | 50937 | |
| 10 | Malopolskie Centrum Medyczne | Kraków | Poland | 30-510 | |
| 11 | Copernicus Memorial Hospital, Department of Hematology | Lodz | Poland | 93-513 | |
| 12 | Maria Skłodowska-Curie Institue of Oncology | Warszawa | Poland | 02-034 | |
| 13 | Instituto Clinico Navarra, Pamplona | Pamplona | Navarra | Spain | 31008 |
| 14 | Institut Català d'Oncologia Av. | Barcelona | Spain | 08010 | |
| 15 | Hospital Vall Hebron | Barcelona | Spain | 08035 | |
| 16 | The Royal Marsden NHS Foundation Trust | Sutton | Surrey | United Kingdom | SM2 5PT |
| 17 | Churchill Hospital: Cancer and Haematology Centre | Oxford | United Kingdom | OX3 8JL |
Sponsors and Collaborators
- Karyopharm Therapeutics Inc
Investigators
- Study Director: Michael Kauffman, MD, PhD, Karyopharm Therapeutics Inc
Study Documents (Full-Text)
None provided.More Information
Publications
- KCP-330-010
Study Results
Participant Flow
| Recruitment Details | This multicenter study was conducted at 30 clinical investigative sites in the United States and Europe. Of the 30 investigative sites, 15 sites enrolled a total of 27 patients in the study. Date first patient enrolled: 14 November 2014 Date last patient completed: 31 August 2016 |
|---|---|
| Pre-assignment Detail | Of the 35 total patients screened, 8 patients were screen-failures. Of the 27 enrolled patients, one patient withdrew from the study prior to receiving treatment. Therefore, a total of 26 patients comprised the Safety population. |
| Arm/Group Title | Selinexor 60 mg/m² (8 Doses/Cycle) | Selinexor 60 mg (6 Doses/Cycle) | Selinexor 60 mg (8 Doses/Cycle) |
|---|---|---|---|
| Arm/Group Description | 60 mg/m² dose twice weekly for weeks 1-4 | 60 mg oral dose twice weekly for weeks 1-3 | 60 mg oral dose twice weekly for weeks 1-4 |
| Period Title: Overall Study | |||
| STARTED | 3 | 15 | 8 |
| COMPLETED | 0 | 0 | 0 |
| NOT COMPLETED | 3 | 15 | 8 |
Baseline Characteristics
| Arm/Group Title | Selinexor 60 mg/m² (8 Doses/Cycle) | Selinexor 60 mg (6 Doses/Cycle) | Selinexor 60 mg (8 Doses/Cycle) | Total |
|---|---|---|---|---|
| Arm/Group Description | 60 mg/m² oral dose twice weekly for Weeks 1-4 | 60 mg oral dose twice weekly for Weeks 1-3 | 60 mg oral dose twice weekly for Weeks 1-4 | Total of all reporting groups |
| Overall Participants | 3 | 15 | 8 | 26 |
| Age (years) [Median (Full Range) ] | ||||
| Median (Full Range) [years] |
68.0
|
68.0
|
69.0
|
68.0
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
2
66.7%
|
3
20%
|
4
50%
|
9
34.6%
|
| Male |
1
33.3%
|
12
80%
|
4
50%
|
17
65.4%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||
| Hispanic or Latino |
1
33.3%
|
1
6.7%
|
0
0%
|
2
7.7%
|
| Not Hispanic or Latino |
1
33.3%
|
14
93.3%
|
8
100%
|
23
88.5%
|
| Unknown or Not Reported |
1
33.3%
|
0
0%
|
0
0%
|
1
3.8%
|
| Race (NIH/OMB) (Count of Participants) | ||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| White |
3
100%
|
15
100%
|
8
100%
|
26
100%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| ECOG score (Count of Participants) | ||||
| Score=0 |
0
0%
|
5
33.3%
|
2
25%
|
7
26.9%
|
| Score=1 |
3
100%
|
6
40%
|
4
50%
|
13
50%
|
| Score=2 |
0
0%
|
4
26.7%
|
1
12.5%
|
5
19.2%
|
| Missing |
0
0%
|
0
0%
|
1
12.5%
|
1
3.8%
|
| Weight (kg) [Median (Full Range) ] | ||||
| Median (Full Range) [kg] |
56.5
|
76.5
|
73.05
|
74.40
|
Outcome Measures
| Title | Percentage of Participants With Overall Response (Overall Response Rate) |
|---|---|
| Description | 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. |
| Time Frame | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Modified Intent to Treat (mITT) population, consisting of all patients who received at least one dose of selinexor and had at least one post-baseline efficacy evaluation. Patients without post-baseline efficacy follow-up information who discontinued the study due to toxicity, disease progression, or death were included in this population. |
| Arm/Group Title | Selinexor |
|---|---|
| Arm/Group Description | All dosing groups |
| Measure Participants | 25 |
| Number (95% Confidence Interval) [Percentage of participants] |
4
133.3%
|
| Title | Number of Participants With Complete Response (CR) |
|---|---|
| Description | 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. |
| Time Frame | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Modified Intent to Treat (mITT) population, consisting of all patients who received at least one dose of selinexor and had at least one post-baseline efficacy evaluation. Patients without post-baseline efficacy follow-up information who discontinued the study due to toxicity, disease progression, or death were included in this population. |
| Arm/Group Title | Selinexor |
|---|---|
| Arm/Group Description | All dosing groups |
| Measure Participants | 25 |
| Count of Participants [Participants] |
0
0%
|
| Title | Number of Participants With Partial Response (PR) |
|---|---|
| Description | 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. |
| Time Frame | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Modified Intent to Treat (mITT) population, consisting of all patients who received at least one dose of selinexor and had at least one post-baseline efficacy evaluation. Patients without post-baseline efficacy follow-up information who discontinued the study due to toxicity, disease progression, or death were included in this population. |
| Arm/Group Title | Selinexor |
|---|---|
| Arm/Group Description | All dosing groups |
| Measure Participants | 25 |
| Count of Participants [Participants] |
1
33.3%
|
| Title | Number of Participants With Stable Disease (SD) |
|---|---|
| Description | 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. |
| Time Frame | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Modified Intent to Treat (mITT) population, consisting of all patients who received at least one dose of selinexor and had at least one post-baseline efficacy evaluation. Patients without post-baseline efficacy follow-up information who discontinued the study due to toxicity, disease progression, or death were included in this population. |
| Arm/Group Title | Selinexor |
|---|---|
| Arm/Group Description | All dosing groups |
| Measure Participants | 25 |
| Count of Participants [Participants] |
6
200%
|
| Title | Number of Participants With Progressive Disease (PD) |
|---|---|
| Description | 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. |
| Time Frame | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Modified Intent to Treat (mITT) population, consisting of all patients who received at least one dose of selinexor and had at least one post-baseline efficacy evaluation. Patients without post-baseline efficacy follow-up information who discontinued the study due to toxicity, disease progression, or death were included in this population. |
| Arm/Group Title | Selinexor |
|---|---|
| Arm/Group Description | All dosing groups |
| Measure Participants | 25 |
| Count of Participants [Participants] |
7
233.3%
|
| Title | Number of Participants With Not Evaluable (NE) Response |
|---|---|
| Description | Number of patients who could not be assessed quantitatively for disease response for any reason. |
| Time Frame | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Modified Intent to Treat (mITT) population, consisting of all patients who received at least one dose of selinexor and had at least one post-baseline efficacy evaluation. Patients without post-baseline efficacy follow-up information who discontinued the study due to toxicity, disease progression, or death were included in this population. |
| Arm/Group Title | Selinexor |
|---|---|
| Arm/Group Description | All dosing groups |
| Measure Participants | 25 |
| Count of Participants [Participants] |
11
366.7%
|
| Title | Percentage of Participants With Disease Control (Disease Control Rate) |
|---|---|
| Description | 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 of bone marrow biopsies by morphologic, immunohistochemistry, and flow cytometry tests. |
| Time Frame | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Modified Intent to Treat (mITT) population, consisting of all patients who received at least one dose of selinexor and had at least one post-baseline efficacy evaluation. Patients without post-baseline efficacy follow-up information who discontinued the study due to toxicity, disease progression, or death were included in this population. |
| Arm/Group Title | Selinexor |
|---|---|
| Arm/Group Description | All dosing groups |
| Measure Participants | 25 |
| Number (95% Confidence Interval) [Percentage of participants] |
28.0
933.3%
|
| Title | Duration of Progression Free Survival (PFS) |
|---|---|
| Description | 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 lesions by PET (positron emission tomography) scan and assessment of bone marrow biopsies by morphologic, immunohistochemistry, and flow cytometry tests. . |
| Time Frame | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Modified Intent to Treat (mITT) population, consisting of all patients who received at least one dose of selinexor and had at least one post-baseline efficacy evaluation. Patients without post-baseline efficacy follow-up information who discontinued the study due to toxicity, disease progression, or death were included in this population. |
| Arm/Group Title | Selinexor |
|---|---|
| Arm/Group Description | All dosing groups |
| Measure Participants | 25 |
| Median (95% Confidence Interval) [Days] |
38.0
|
Adverse Events
| Time Frame | Treatment-emergent AEs were collected from the first day of dosing (Cycle 1 Day 1) through the 30-day follow-up. | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||
| Arm/Group Title | Selinexor 60 mg/m² (8 Doses/Cycle) | Selinexor 60 mg (6 Doses/Cycle) | Selinexor 60 mg (8 Doses/Cycle) | |||
| Arm/Group Description | 60 mg/m² oral dose twice weekly for Weeks 1-4 | 60 mg oral dose twice weekly for Weeks 1-3 | 60 mg oral dose twice weekly for Weeks 1-4 | |||
All Cause Mortality |
||||||
| Selinexor 60 mg/m² (8 Doses/Cycle) | Selinexor 60 mg (6 Doses/Cycle) | Selinexor 60 mg (8 Doses/Cycle) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/3 (33.3%) | 8/15 (53.3%) | 2/8 (25%) | |||
Serious Adverse Events |
||||||
| Selinexor 60 mg/m² (8 Doses/Cycle) | Selinexor 60 mg (6 Doses/Cycle) | Selinexor 60 mg (8 Doses/Cycle) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/3 (100%) | 9/15 (60%) | 5/8 (62.5%) | |||
| Blood and lymphatic system disorders | ||||||
| Febrile Neutropenia | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Thrombocytopenia | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Cardiac disorders | ||||||
| Supraventricular Tachycardia | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| General disorders | ||||||
| Asthenia | 1/3 (33.3%) | 0/15 (0%) | 0/8 (0%) | |||
| Fatigue | 1/3 (33.3%) | 0/15 (0%) | 0/8 (0%) | |||
| General Physical Health Deterioration | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Mucosal Inflammation | 1/3 (33.3%) | 0/15 (0%) | 0/8 (0%) | |||
| Pyrexia | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Infections and infestations | ||||||
| Sepsis | 0/3 (0%) | 1/15 (6.7%) | 2/8 (25%) | |||
| Pneumonia | 1/3 (33.3%) | 0/15 (0%) | 1/8 (12.5%) | |||
| Staphylococcal Infection | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Investigations | ||||||
| Clostridium Test Positive | 0/3 (0%) | 0/15 (0%) | 1/8 (12.5%) | |||
| Metabolism and nutrition disorders | ||||||
| Decreased Appetite | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Dehydration | 1/3 (33.3%) | 0/15 (0%) | 0/8 (0%) | |||
| Food Intolerance | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Hypercalcaemia | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Back Pain | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Tumour Haemorrhage | 0/3 (0%) | 0/15 (0%) | 1/8 (12.5%) | |||
| Nervous system disorders | ||||||
| Cerebral Haemorrhage | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Haemorrhage Intracranial | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Neuropathy Peripheral | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Renal and urinary disorders | ||||||
| Acute Kidney Injury | 1/3 (33.3%) | 0/15 (0%) | 0/8 (0%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Dyspnoea | 1/3 (33.3%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Respiratory Failure | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Vascular disorders | ||||||
| Deep Vein Thrombosis | 0/3 (0%) | 0/15 (0%) | 1/8 (12.5%) | |||
| Embolism Arterial | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| Selinexor 60 mg/m² (8 Doses/Cycle) | Selinexor 60 mg (6 Doses/Cycle) | Selinexor 60 mg (8 Doses/Cycle) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/3 (100%) | 15/15 (100%) | 7/8 (87.5%) | |||
| Blood and lymphatic system disorders | ||||||
| Thrombocytopenia | 1/3 (33.3%) | 8/15 (53.3%) | 5/8 (62.5%) | |||
| Anaemia | 1/3 (33.3%) | 5/15 (33.3%) | 1/8 (12.5%) | |||
| Neutropenia | 0/3 (0%) | 3/15 (20%) | 3/8 (37.5%) | |||
| Leukopenia | 1/3 (33.3%) | 2/15 (13.3%) | 2/8 (25%) | |||
| Leukocytosis | 0/3 (0%) | 2/15 (13.3%) | 0/8 (0%) | |||
| Pancytopenia | 1/3 (33.3%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Febrile Neutropenia | 1/3 (33.3%) | 0/15 (0%) | 0/8 (0%) | |||
| Cardiac disorders | ||||||
| Tachycardia | 1/3 (33.3%) | 0/15 (0%) | 0/8 (0%) | |||
| Ear and labyrinth disorders | ||||||
| Deafness | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Vertigo | 1/3 (33.3%) | 0/15 (0%) | 0/8 (0%) | |||
| Endocrine disorders | ||||||
| Hypothyroidism | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Eye disorders | ||||||
| Eye Irritation | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Ocular Toxicity | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Photophobia | 0/3 (0%) | 0/15 (0%) | 1/8 (12.5%) | |||
| Vision Blurred | 0/3 (0%) | 0/15 (0%) | 1/8 (12.5%) | |||
| Gastrointestinal disorders | ||||||
| Nausea | 2/3 (66.7%) | 8/15 (53.3%) | 3/8 (37.5%) | |||
| Diarrhea | 1/3 (33.3%) | 5/15 (33.3%) | 3/8 (37.5%) | |||
| Vomiting | 1/3 (33.3%) | 7/15 (46.7%) | 1/8 (12.5%) | |||
| Constipation | 1/3 (33.3%) | 2/15 (13.3%) | 2/8 (25%) | |||
| Abdominal Pain | 0/3 (0%) | 2/15 (13.3%) | 0/8 (0%) | |||
| Anal Incontinence | 0/3 (0%) | 2/15 (13.3%) | 0/8 (0%) | |||
| Dry Mouth | 0/3 (0%) | 2/15 (13.3%) | 0/8 (0%) | |||
| Abdominal Pain Lower | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Abdominal Pain Upper | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Dyspepsia | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Melaena | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Rectal Haemorrhage | 1/3 (33.3%) | 0/15 (0%) | 0/8 (0%) | |||
| Stomatitis | 0/3 (0%) | 0/15 (0%) | 1/8 (12.5%) | |||
| Tongue Coated | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| General disorders | ||||||
| Pyrexia | 1/3 (33.3%) | 6/15 (40%) | 2/8 (25%) | |||
| Fatigue | 2/3 (66.7%) | 4/15 (26.7%) | 2/8 (25%) | |||
| Asthenia | 1/3 (33.3%) | 4/15 (26.7%) | 2/8 (25%) | |||
| Oedema Peripheral | 0/3 (0%) | 5/15 (33.3%) | 1/8 (12.5%) | |||
| General Physical Health Deterioration | 1/3 (33.3%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Mucosal Inflammation | 1/3 (33.3%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Early Satiety | 0/3 (0%) | 0/15 (0%) | 1/8 (12.5%) | |||
| Facial Pain | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Oedema | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Pain | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Hepatobiliary disorders | ||||||
| Hyperbilirubinaemia | 0/3 (0%) | 2/15 (13.3%) | 0/8 (0%) | |||
| Jaundice | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Infections and infestations | ||||||
| Oral Candidiasis | 0/3 (0%) | 1/15 (6.7%) | 2/8 (25%) | |||
| Urinary Tract Infection | 1/3 (33.3%) | 1/15 (6.7%) | 1/8 (12.5%) | |||
| Oral Infection | 0/3 (0%) | 2/15 (13.3%) | 0/8 (0%) | |||
| Upper Respiratory Tract Infection | 0/3 (0%) | 1/15 (6.7%) | 1/8 (12.5%) | |||
| Bacteriuria | 0/3 (0%) | 0/15 (0%) | 1/8 (12.5%) | |||
| Clostridium Difficile Infection | 0/3 (0%) | 0/15 (0%) | 1/8 (12.5%) | |||
| Device Related Infection | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Herpes Ophthalmic | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Oral Herpes | 1/3 (33.3%) | 0/15 (0%) | 0/8 (0%) | |||
| Osteomyelitis | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Pneumonia | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Respiratory Tract Infection | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Sepsis | 1/3 (33.3%) | 0/15 (0%) | 0/8 (0%) | |||
| Sinusitis | 0/3 (0%) | 0/15 (0%) | 1/8 (12.5%) | |||
| Injury, poisoning and procedural complications | ||||||
| Fall | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Post Procedural Haematoma | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Skain Abrasion | 0/3 (0%) | 0/15 (0%) | 1/8 (12.5%) | |||
| Investigations | ||||||
| Blood Alkaline Phosphatase Increased | 1/3 (33.3%) | 2/15 (13.3%) | 1/8 (12.5%) | |||
| Weight Decreased | 0/3 (0%) | 0/15 (0%) | 3/8 (37.5%) | |||
| C-Reactive Protein Increased | 0/3 (0%) | 2/15 (13.3%) | 0/8 (0%) | |||
| Gamma-Glutamyltransferase Increased | 0/3 (0%) | 2/15 (13.3%) | 0/8 (0%) | |||
| Aspartate Aminotransferase Increased | 1/3 (33.3%) | 0/15 (0%) | 0/8 (0%) | |||
| Blood Creatinine Phophokinase Decreased | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Blood Creatinine Phosphokinase Increased | 1/3 (33.3%) | 0/15 (0%) | 0/8 (0%) | |||
| Hypophonesis | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| International Normalised Ratio Increased | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Metabolism and nutrition disorders | ||||||
| Decreased Appetite | 2/3 (66.7%) | 5/15 (33.3%) | 2/8 (25%) | |||
| Hyponatraemia | 1/3 (33.3%) | 4/15 (26.7%) | 2/8 (25%) | |||
| Hypokalaemia | 1/3 (33.3%) | 1/15 (6.7%) | 3/8 (37.5%) | |||
| Hypocalcaemia | 1/3 (33.3%) | 1/15 (6.7%) | 2/8 (25%) | |||
| Hypercalcaemia | 1/3 (33.3%) | 2/15 (13.3%) | 0/8 (0%) | |||
| Hyperglycaemia | 1/3 (33.3%) | 1/15 (6.7%) | 1/8 (12.5%) | |||
| Hypoalbuminaemia | 0/3 (0%) | 2/15 (13.3%) | 1/8 (12.5%) | |||
| Hypomagnesaemia | 0/3 (0%) | 2/15 (13.3%) | 1/8 (12.5%) | |||
| Hypercreatininaemia | 0/3 (0%) | 1/15 (6.7%) | 1/8 (12.5%) | |||
| Cachexia | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Dehydration | 0/3 (0%) | 0/15 (0%) | 1/8 (12.5%) | |||
| Hyperkalaemia | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Hypermagnesaemia | 0/3 (0%) | 0/15 (0%) | 1/8 (12.5%) | |||
| Hypochloraemia | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Hypophosphataemia | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Back Pain | 1/3 (33.3%) | 4/15 (26.7%) | 0/8 (0%) | |||
| Arthralgia | 0/3 (0%) | 1/15 (6.7%) | 1/8 (12.5%) | |||
| Hypercreatinaemia | 0/3 (0%) | 0/15 (0%) | 2/8 (25%) | |||
| Pain In Extremity | 0/3 (0%) | 2/15 (13.3%) | 0/8 (0%) | |||
| Groin Pain | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Muscular Weakness | 0/3 (0%) | 0/15 (0%) | 1/8 (12.5%) | |||
| Musculoskeletal Chest Pain | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Myopathy | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Tumour Pain | 0/3 (0%) | 0/15 (0%) | 2/8 (25%) | |||
| Tumour Associated Fever | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Nervous system disorders | ||||||
| Dizziness | 0/3 (0%) | 1/15 (6.7%) | 4/8 (50%) | |||
| Headache | 0/3 (0%) | 3/15 (20%) | 0/8 (0%) | |||
| Dysgeusia | 0/3 (0%) | 1/15 (6.7%) | 1/8 (12.5%) | |||
| Aphasia | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Ataxia | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Horner's Syndrome | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Hypokinesia | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Lethargy | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Migraine With Aura | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Nervous System Disorder | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Paraesthesia | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Visual Field Defect | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Psychiatric disorders | ||||||
| Confusional State | 0/3 (0%) | 0/15 (0%) | 1/8 (12.5%) | |||
| Insomnia | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Renal and urinary disorders | ||||||
| Pollakiuria | 0/3 (0%) | 1/15 (6.7%) | 1/8 (12.5%) | |||
| Urinary Incontinence | 0/3 (0%) | 2/15 (13.3%) | 0/8 (0%) | |||
| Haematuria | 0/3 (0%) | 0/15 (0%) | 1/8 (12.5%) | |||
| Incontinence | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Renal Failure | 0/3 (0%) | 0/15 (0%) | 1/8 (12.5%) | |||
| Reproductive system and breast disorders | ||||||
| Oedema Genital | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Pelvic Pain | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Cough | 1/3 (33.3%) | 1/15 (6.7%) | 3/8 (37.5%) | |||
| Dyspnoea | 0/3 (0%) | 2/15 (13.3%) | 1/8 (12.5%) | |||
| Haemoptysis | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Nasal Congestion | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Oropharyngeal Pain | 0/3 (0%) | 0/15 (0%) | 1/8 (12.5%) | |||
| Pleural Effusion | 0/3 (0%) | 0/15 (0%) | 1/8 (12.5%) | |||
| Pulmonary Embolism | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Rhinorrhoea | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Dry Skin | 1/3 (33.3%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Erythema | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Pruritus | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Skin Discolouration | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Skin Lesion | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Vascular disorders | ||||||
| Hypotension | 2/3 (66.7%) | 0/15 (0%) | 2/8 (25%) | |||
| Haematoma | 1/3 (33.3%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Deep Vein Thrombosis | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Embolism | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Haemorrhage | 0/3 (0%) | 0/15 (0%) | 1/8 (12.5%) | |||
| Hot Flush | 1/3 (33.3%) | 0/15 (0%) | 0/8 (0%) | |||
| Hypertension | 0/3 (0%) | 0/15 (0%) | 1/8 (12.5%) | |||
| Pallor | 1/3 (33.3%) | 0/15 (0%) | 0/8 (0%) | |||
| Phlebitis | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
| Post Procedural Contusion | 0/3 (0%) | 1/15 (6.7%) | 0/8 (0%) | |||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Jatin Shah, MD |
|---|---|
| Organization | Karyopharm Therapeutics Inc. |
| Phone | (617) 658-0600 |
| jshah@karyopharm.com |
- KCP-330-010