Trial Outcomes & Findings for Selective Inhibitor of Nuclear Export (SINE) Selinexor (KPT-330) in Patients With Myelodysplastic Syndromes (NCT NCT02228525)

Last Updated: 2022-03-09

Results Overview

Using a Simon's two-stage minimax design, this trial will accrue a maximum of 20 patients. Early termination may occur if no responses are observed in the first 13 patients. If at least one response is observed, the trial will continue to the maximum sample size. At the end of the trial, the treatment strategy will be considered promising in this patient population if at least 3 patients achieve a response. The type I and type II errors are set at 0.10.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

25 participants

Primary outcome timeframe

2 years

Results posted on

2022-03-09

Participant Flow

Participant milestones

Participant milestones
Measure	Selinexor (KPT-330) Patients with myelodysplastic syndromes who are refractory to hypomethylating agents (decitabine or 5-azacytidine) will receive oral selinexor at a starting dose of 60 mg twice weekly for 2 weeks, followed by 1 week of no therapy. Dose reductions are permitted for patients who are benefiting from selinexor but have poor tolerance. After discontinuation from treatment, patients will be followed by the study staff for survival status approximately every three months. selinexor (KPT-330)
Overall Study STARTED	25
Overall Study COMPLETED	25
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Selective Inhibitor of Nuclear Export (SINE) Selinexor (KPT-330) in Patients With Myelodysplastic Syndromes

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Selinexor (KPT-330) n=25 Participants Patients with myelodysplastic syndromes who are refractory to hypomethylating agents (decitabine or 5-azacytidine) will receive oral selinexor at a starting dose of 60 mg twice weekly for 2 weeks, followed by 1 week of no therapy. Dose reductions are permitted for patients who are benefiting from selinexor but have poor tolerance. After discontinuation from treatment, patients will be followed by the study staff for survival status approximately every three months. selinexor (KPT-330)
Age, Continuous	77 years n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants
Sex: Female, Male Male	21 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	17 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	23 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Region of Enrollment United States	25 Participants n=5 Participants

PRIMARY outcome

Timeframe: 2 years

Outcome measures

Outcome measures
Measure	Selinexor (KPT-330) n=25 Participants Patients with myelodysplastic syndromes who are refractory to hypomethylating agents (decitabine or 5-azacytidine) will receive oral selinexor at a starting dose of 60 mg twice weekly for 2 weeks, followed by 1 week of no therapy. Dose reductions are permitted for patients who are benefiting from selinexor but have poor tolerance. After discontinuation from treatment, patients will be followed by the study staff for survival status approximately every three months. selinexor (KPT-330)
Best Overall Response Rate	26 Percentage of participants with response Interval 10.0 to 48.0

SECONDARY outcome

Timeframe: 2 years

Response duration will be calculated among patients who achieve a response of HI, mCR, PR or CR using Kaplan-Meier methodology. Median duration of response and the corresponding 95% confidence interval will be estimated.

Outcome measures

Outcome measures
Measure	Selinexor (KPT-330) n=25 Participants Patients with myelodysplastic syndromes who are refractory to hypomethylating agents (decitabine or 5-azacytidine) will receive oral selinexor at a starting dose of 60 mg twice weekly for 2 weeks, followed by 1 week of no therapy. Dose reductions are permitted for patients who are benefiting from selinexor but have poor tolerance. After discontinuation from treatment, patients will be followed by the study staff for survival status approximately every three months. selinexor (KPT-330)
Response Duration	6.3 months Interval 2.1 to 7.8

SECONDARY outcome

Timeframe: 2 years

Overall survival from the time of study enrollment will be calculated using Kaplan-Meier methodology. Overall survival curves will be displayed for the study population along with selected quantiles and corresponding 95% confidence intervals of survival.

Outcome measures

Outcome measures
Measure	Selinexor (KPT-330) n=25 Participants Patients with myelodysplastic syndromes who are refractory to hypomethylating agents (decitabine or 5-azacytidine) will receive oral selinexor at a starting dose of 60 mg twice weekly for 2 weeks, followed by 1 week of no therapy. Dose reductions are permitted for patients who are benefiting from selinexor but have poor tolerance. After discontinuation from treatment, patients will be followed by the study staff for survival status approximately every three months. selinexor (KPT-330)
Overall Survival	8.5 months Interval 6.7 to 12.2

SECONDARY outcome

Timeframe: 2 years

The safety and tolerability of Selinexor and ST will be evaluated by means of drug related AE reports, physical examinations, and laboratory safety evaluations. Common Terminology Criteria for Adverse Events (CTCAE) V4.03 will be used for grading of AEs.

Outcome measures

Outcome measures
Measure	Selinexor (KPT-330) n=25 Participants Patients with myelodysplastic syndromes who are refractory to hypomethylating agents (decitabine or 5-azacytidine) will receive oral selinexor at a starting dose of 60 mg twice weekly for 2 weeks, followed by 1 week of no therapy. Dose reductions are permitted for patients who are benefiting from selinexor but have poor tolerance. After discontinuation from treatment, patients will be followed by the study staff for survival status approximately every three months. selinexor (KPT-330)
Participants Evaluated for Adverse Events	25 Participants

Adverse Events

Selinexor (KPT-330)

Serious events: 0 serious events

Other events: 25 other events

Deaths: 7 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Selinexor (KPT-330) n=25 participants at risk Patients with myelodysplastic syndromes who are refractory to hypomethylating agents (decitabine or 5-azacytidine) will receive oral selinexor at a starting dose of 60 mg twice weekly for 2 weeks, followed by 1 week of no therapy. Dose reductions are permitted for patients who are benefiting from selinexor but have poor tolerance. After discontinuation from treatment, patients will be followed by the study staff for survival status approximately every three months. selinexor (KPT-330)
Metabolism and nutrition disorders Anorexia or weight loss	40.0% 10/25 • 2 years
General disorders Fatigue	56.0% 14/25 • 2 years
General disorders Malaise	8.0% 2/25 • 2 years
Gastrointestinal disorders Diarrhea	20.0% 5/25 • 2 years
Nervous system disorders Dysgeusia	16.0% 4/25 • 2 years
Investigations Increased alanine aminotransferase	8.0% 2/25 • 2 years
Metabolism and nutrition disorders Hyperglycaemia	36.0% 9/25 • 2 years
Metabolism and nutrition disorders Hyperkalaemia	8.0% 2/25 • 2 years
Metabolism and nutrition disorders Hypoalbuminaemia	24.0% 6/25 • 2 years
Metabolism and nutrition disorders Hypocalcaemia	12.0% 3/25 • 2 years
Metabolism and nutrition disorders Hyponatraemia	44.0% 11/25 • 2 years
Gastrointestinal disorders Nausea or vomiting	56.0% 14/25 • 2 years
Investigations Decreased white blood cell count	16.0% 4/25 • 2 years
Investigations Decreased neutrophil count	28.0% 7/25 • 2 years
Blood and lymphatic system disorders Febrile neutropenia	8.0% 2/25 • 2 years
Blood and lymphatic system disorders Anaemia	12.0% 3/25 • 2 years
Investigations Decreased platelet count	48.0% 12/25 • 2 years

Additional Information

Dr. Eytan Stein, MD

Memorial Sloan Kettering Cancer Center

Phone: 646-608-3749

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place