Trial Outcomes & Findings for Phase I/II, Study of Selective Inhibitor of Nuclear Export (SINE) Selinexor (KPT-330) + Sorafenib in Acute Myeloid Leukemia (NCT NCT02530476)
NCT ID: NCT02530476
Last Updated: 2020-03-31
Results Overview
MTD defined as the highest dose level with \</= 1 out of 6 patients experience a dose limiting toxicity (DLT) during the first 28 days of treatment.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
17 participants
Primary outcome timeframe
28 days
Results posted on
2020-03-31
Participant Flow
Recruitment Period: December 2015 to July 2018
Participant milestones
| Measure |
Phase I Group 1 Selinexor + Sorafenib
Cohort includes those with FLT3-ITD and -D835 mutated participants with relapsed/refractory AML, including participants who may have been previously exposed to one or more FLT3-inhibitors.
Phase I Starting Dose of Sorafenib: 400 mg by mouth twice daily for a 28 day cycle.
Phase I Starting Dose of Selinexor: 80 mg by mouth twice weekly for a 28 day cycle.
Selinexor: Phase I Starting Dose of Selinexor: 80 mg by mouth twice weekly for a 28 day cycle.
Phase II Starting Dose of Selinexor: Maximum tolerated dose from Phase I.
Sorafenib: Phase I Starting Dose of Sorafenib: 400 mg by mouth twice daily for a 28 day cycle.
Phase II Starting Dose of Sorafenib: Maximum tolerated dose combination from Phase I.
|
Phase I Group 2 Selinexor + Sorafenib
Cohort includes those with FLT3-ITD and -D835 mutated participants with relapsed/refractory AML, including participants who may have been previously exposed to one or more FLT3-inhibitors.
Phase I Starting Dose of Sorafenib: 400 mg by mouth twice daily for a 28 day cycle.
Phase I Starting Dose of Selinexor: 80 mg by mouth twice weekly for a 28 day cycle. Phase I Group 2 received Selinexor 80 mg by mouth twice weekly for a 28 day cycle.
|
Cohort 1 (FLT3-ITD Inhibitor Failure Cohort)
Cohort includes those with FLT3-ITD and -D835 mutated relapsed/refractory AML who have failed therapy with up to two prior salvage regimens.
Phase II Starting Dose of Sorafenib: Maximum tolerated dose combination from Phase I.
Phase II Starting Dose of Selinexor: Maximum tolerated dose from Phase I.
Selinexor: Phase I Starting Dose of Selinexor: 80 mg by mouth twice weekly for a 28 day cycle.
Phase II Starting Dose of Selinexor: Maximum tolerated dose from Phase I.
Sorafenib: Phase I Starting Dose of Sorafenib: 400 mg by mouth twice daily for a 28 day cycle.
Phase II Starting Dose of Sorafenib: Maximum tolerated dose combination from Phase I.
|
Cohort 2 (FLT3-ITD Inhibitor Naive Cohort)
Cohort includes those with FLT3-ITD and -D835 mutated relapsed/refractory AML who have failed therapy with up to two prior salvage regimens.
Phase II Starting Dose of Sorafenib: Maximum tolerated dose combination from Phase I.
Phase II Starting Dose of Selinexor: Maximum tolerated dose from Phase I.
Selinexor: Phase I Starting Dose of Selinexor: 80 mg by mouth twice weekly for a 28 day cycle.
Phase II Starting Dose of Selinexor: Maximum tolerated dose from Phase I.
Sorafenib: Phase I Starting Dose of Sorafenib: 400 mg by mouth twice daily for a 28 day cycle.
Phase II Starting Dose of Sorafenib: Maximum tolerated dose combination from Phase I.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
4
|
3
|
7
|
3
|
|
Overall Study
COMPLETED
|
4
|
3
|
7
|
3
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Phase I/II, Study of Selective Inhibitor of Nuclear Export (SINE) Selinexor (KPT-330) + Sorafenib in Acute Myeloid Leukemia
Baseline characteristics by cohort
| Measure |
Phase I Group 1 Selinexor + Sorafenib
n=4 Participants
Cohort includes those with FLT3-ITD and -D835 mutated participants with relapsed/refractory AML, including participants who may have been previously exposed to one or more FLT3-inhibitors.
Phase I Starting Dose of Sorafenib: 400 mg by mouth twice daily for a 28 day cycle.
Phase I Starting Dose of Selinexor: 80 mg by mouth twice weekly for a 28 day cycle.
Selinexor: Phase I Starting Dose of Selinexor: 80 mg by mouth twice weekly for a 28 day cycle.
Phase II Starting Dose of Selinexor: Maximum tolerated dose from Phase I.
Sorafenib: Phase I Starting Dose of Sorafenib: 400 mg by mouth twice daily for a 28 day cycle.
Phase II Starting Dose of Sorafenib: Maximum tolerated dose combination from Phase I.
|
Phase I Group 2 Selinexor + Sorafenib
n=3 Participants
Cohort includes those with FLT3-ITD and -D835 mutated participants with relapsed/refractory AML, including participants who may have been previously exposed to one or more FLT3-inhibitors.
Phase I Starting Dose of Sorafenib: 400 mg by mouth twice daily for a 28 day cycle.
Phase I Starting Dose of Selinexor: 80 mg by mouth twice weekly for a 28 day cycle. Phase I Group 2 received Selinexor 80 mg by mouth twice weekly for a 28 day cycle.
|
Cohort 1 (FLT3-ITD Inhibitor Failure Cohort)
n=7 Participants
Cohort includes those with FLT3-ITD and -D835 mutated relapsed/refractory AML who have failed therapy with up to two prior salvage regimens.
Phase II Starting Dose of Sorafenib: Maximum tolerated dose combination from Phase I.
Phase II Starting Dose of Selinexor: Maximum tolerated dose from Phase I.
Selinexor: Phase I Starting Dose of Selinexor: 80 mg by mouth twice weekly for a 28 day cycle.
Phase II Starting Dose of Selinexor: Maximum tolerated dose from Phase I.
Sorafenib: Phase I Starting Dose of Sorafenib: 400 mg by mouth twice daily for a 28 day cycle.
Phase II Starting Dose of Sorafenib: Maximum tolerated dose combination from Phase I.
|
Cohort 2 (FLT3-ITD Inhibitor Naive Cohort)
n=3 Participants
Cohort includes those with FLT3-ITD and -D835 mutated relapsed/refractory AML who have failed therapy with up to two prior salvage regimens.
Phase II Starting Dose of Sorafenib: Maximum tolerated dose combination from Phase I.
Phase II Starting Dose of Selinexor: Maximum tolerated dose from Phase I.
Selinexor: Phase I Starting Dose of Selinexor: 80 mg by mouth twice weekly for a 28 day cycle.
Phase II Starting Dose of Selinexor: Maximum tolerated dose from Phase I.
Sorafenib: Phase I Starting Dose of Sorafenib: 400 mg by mouth twice daily for a 28 day cycle.
Phase II Starting Dose of Sorafenib: Maximum tolerated dose combination from Phase I.
|
Total
n=17 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
6 Participants
n=21 Participants
|
|
Age, Categorical
>=65 years
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
11 Participants
n=21 Participants
|
|
Age, Continuous
|
78.5 years
n=5 Participants
|
68 years
n=7 Participants
|
63 years
n=5 Participants
|
77 years
n=4 Participants
|
68 years
n=21 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
9 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
8 Participants
n=21 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
5 Participants
n=21 Participants
|
|
Race (NIH/OMB)
White
|
4 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
9 Participants
n=21 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
|
Region of Enrollment
United States
|
4 participants
n=5 Participants
|
3 participants
n=7 Participants
|
6 participants
n=5 Participants
|
3 participants
n=4 Participants
|
16 participants
n=21 Participants
|
PRIMARY outcome
Timeframe: 28 daysPopulation: The Outcome Measure of MTD was the objective of the Phase I Selinexor + Sorafenib cohort only. Data for MTD were not collected for patients on Cohorts 1 and 2.
MTD defined as the highest dose level with \</= 1 out of 6 patients experience a dose limiting toxicity (DLT) during the first 28 days of treatment.
Outcome measures
| Measure |
Phase I Group 1 Selinexor + Sorafenib
n=4 Participants
Cohort includes those with FLT3-ITD and -D835 mutated participants with relapsed/refractory AML, including participants who may have been previously exposed to one or more FLT3-inhibitors.
Phase I Starting Dose of Sorafenib: 400 mg by mouth twice daily for a 28 day cycle.
Phase I Starting Dose of Selinexor: 80 mg by mouth twice weekly for a 28 day cycle.
Selinexor: Phase I Starting Dose of Selinexor: 80 mg by mouth twice weekly for a 28 day cycle.
Phase II Starting Dose of Selinexor: Maximum tolerated dose from Phase I.
Sorafenib: Phase I Starting Dose of Sorafenib: 400 mg by mouth twice daily for a 28 day cycle.
Phase II Starting Dose of Sorafenib: Maximum tolerated dose combination from Phase I.
|
Phase I Group 2 Selinexor + Sorafenib
n=3 Participants
Cohort includes those with FLT3-ITD and -D835 mutated participants with relapsed/refractory AML, including participants who may have been previously exposed to one or more FLT3-inhibitors.
Phase I Starting Dose of Sorafenib: 400 mg by mouth twice daily for a 28 day cycle.
Phase I Starting Dose of Selinexor: 80 mg by mouth twice weekly for a 28 day cycle. Phase I Group 2 received Selinexor 80 mg by mouth twice weekly for a 28 day cycle.
|
Cohort 1 (FLT3-ITD Inhibitor Failure Cohort)
Cohort includes those with FLT3-ITD and -D835 mutated relapsed/refractory AML who have failed therapy with up to two prior salvage regimens.
Phase II Starting Dose of Sorafenib: Maximum tolerated dose combination from Phase I.
Phase II Starting Dose of Selinexor: Maximum tolerated dose from Phase I.
Selinexor: Phase I Starting Dose of Selinexor: 80 mg by mouth twice weekly for a 28 day cycle.
Phase II Starting Dose of Selinexor: Maximum tolerated dose from Phase I.
Sorafenib: Phase I Starting Dose of Sorafenib: 400 mg by mouth twice daily for a 28 day cycle.
Phase II Starting Dose of Sorafenib: Maximum tolerated dose combination from Phase I.
|
Cohort 2 (FLT3-ITD Inhibitor Naive Cohort)
Cohort includes those with FLT3-ITD and -D835 mutated relapsed/refractory AML who have failed therapy with up to two prior salvage regimens.
Phase II Starting Dose of Sorafenib: Maximum tolerated dose combination from Phase I.
Phase II Starting Dose of Selinexor: Maximum tolerated dose from Phase I.
Selinexor: Phase I Starting Dose of Selinexor: 80 mg by mouth twice weekly for a 28 day cycle.
Phase II Starting Dose of Selinexor: Maximum tolerated dose from Phase I.
Sorafenib: Phase I Starting Dose of Sorafenib: 400 mg by mouth twice daily for a 28 day cycle.
Phase II Starting Dose of Sorafenib: Maximum tolerated dose combination from Phase I.
|
|---|---|---|---|---|
|
Maximum Tolerated Dose (MTD) of Selinexor With Sorafenib
|
60 Milligrams
|
60 Milligrams
|
—
|
—
|
PRIMARY outcome
Timeframe: 84 days, assessed following first three cycles of therapy of Selinexor with SorafenibPopulation: Of the four participants in the Phase I Group 1 Selinexor + Sorafenib arm, one participant was not evaluable for response. Of the seven participants in cohort 1, one participant was not evaluable for response. Of the three participants in cohort 2, one participant was not evaluable for response.
CRc Response criteria modified from International Working Group for AML. Responders obtain a Composite Complete Remission Rate (CRc) with or without cytogenetic response, hematologic improvements, and morphologic leukemia-free state. CRc rate is defined as the confirmed remission rate of all complete and incomplete CRs (i.e., CR+ CRp + CRi). CR: bone marrow regenerating normal hematopoietic cells \& morphologic leukemia-free state, \& ANC \> 1×10\^9/L, platelet count ≥100×10\^9/L, \& normal marrow differential with \<5% blasts, \& red blood cell (RBC) and platelet transfusion independent, no evidence of extramedullary leukemia. CRp: CR except for incomplete platelet recovery (\<100×10\^9/L). CRi: Same criteria for CR except incomplete hematological recovery with residual neutropenia (ANC ≤ 1 × 109/L) with or without thrombocytopenia (platelet count \<100×109/L). No need to be RBC or platelet transfusion independent (modification to Cheson criteria).
Outcome measures
| Measure |
Phase I Group 1 Selinexor + Sorafenib
n=3 Participants
Cohort includes those with FLT3-ITD and -D835 mutated participants with relapsed/refractory AML, including participants who may have been previously exposed to one or more FLT3-inhibitors.
Phase I Starting Dose of Sorafenib: 400 mg by mouth twice daily for a 28 day cycle.
Phase I Starting Dose of Selinexor: 80 mg by mouth twice weekly for a 28 day cycle.
Selinexor: Phase I Starting Dose of Selinexor: 80 mg by mouth twice weekly for a 28 day cycle.
Phase II Starting Dose of Selinexor: Maximum tolerated dose from Phase I.
Sorafenib: Phase I Starting Dose of Sorafenib: 400 mg by mouth twice daily for a 28 day cycle.
Phase II Starting Dose of Sorafenib: Maximum tolerated dose combination from Phase I.
|
Phase I Group 2 Selinexor + Sorafenib
n=3 Participants
Cohort includes those with FLT3-ITD and -D835 mutated participants with relapsed/refractory AML, including participants who may have been previously exposed to one or more FLT3-inhibitors.
Phase I Starting Dose of Sorafenib: 400 mg by mouth twice daily for a 28 day cycle.
Phase I Starting Dose of Selinexor: 80 mg by mouth twice weekly for a 28 day cycle. Phase I Group 2 received Selinexor 80 mg by mouth twice weekly for a 28 day cycle.
|
Cohort 1 (FLT3-ITD Inhibitor Failure Cohort)
n=6 Participants
Cohort includes those with FLT3-ITD and -D835 mutated relapsed/refractory AML who have failed therapy with up to two prior salvage regimens.
Phase II Starting Dose of Sorafenib: Maximum tolerated dose combination from Phase I.
Phase II Starting Dose of Selinexor: Maximum tolerated dose from Phase I.
Selinexor: Phase I Starting Dose of Selinexor: 80 mg by mouth twice weekly for a 28 day cycle.
Phase II Starting Dose of Selinexor: Maximum tolerated dose from Phase I.
Sorafenib: Phase I Starting Dose of Sorafenib: 400 mg by mouth twice daily for a 28 day cycle.
Phase II Starting Dose of Sorafenib: Maximum tolerated dose combination from Phase I.
|
Cohort 2 (FLT3-ITD Inhibitor Naive Cohort)
n=2 Participants
Cohort includes those with FLT3-ITD and -D835 mutated relapsed/refractory AML who have failed therapy with up to two prior salvage regimens.
Phase II Starting Dose of Sorafenib: Maximum tolerated dose combination from Phase I.
Phase II Starting Dose of Selinexor: Maximum tolerated dose from Phase I.
Selinexor: Phase I Starting Dose of Selinexor: 80 mg by mouth twice weekly for a 28 day cycle.
Phase II Starting Dose of Selinexor: Maximum tolerated dose from Phase I.
Sorafenib: Phase I Starting Dose of Sorafenib: 400 mg by mouth twice daily for a 28 day cycle.
Phase II Starting Dose of Sorafenib: Maximum tolerated dose combination from Phase I.
|
|---|---|---|---|---|
|
Composite CR (CRc) Rate Defined as CR (Complete Remission) + CRp (Complete Remission With Incomplete Platelet Recovery) + CRi (Complete Remission With Incomplete Count Recovery) Within 3 Months of Treatment Initiation
|
2 Participants
|
0 Participants
|
3 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to 15 months, on average 5 monthsPopulation: Overall Survival was not an objective outlined for participants in Phase I Group's 1 and 2, therefore overall survival was not done for these participants. Of the seven participants in cohort 1, one participant was not evaluable for response. Of the three participants in cohort 2, one participant was not evaluable for response.
Time from date of treatment start until date of death due to any cause or last Follow-up.
Outcome measures
| Measure |
Phase I Group 1 Selinexor + Sorafenib
Cohort includes those with FLT3-ITD and -D835 mutated participants with relapsed/refractory AML, including participants who may have been previously exposed to one or more FLT3-inhibitors.
Phase I Starting Dose of Sorafenib: 400 mg by mouth twice daily for a 28 day cycle.
Phase I Starting Dose of Selinexor: 80 mg by mouth twice weekly for a 28 day cycle.
Selinexor: Phase I Starting Dose of Selinexor: 80 mg by mouth twice weekly for a 28 day cycle.
Phase II Starting Dose of Selinexor: Maximum tolerated dose from Phase I.
Sorafenib: Phase I Starting Dose of Sorafenib: 400 mg by mouth twice daily for a 28 day cycle.
Phase II Starting Dose of Sorafenib: Maximum tolerated dose combination from Phase I.
|
Phase I Group 2 Selinexor + Sorafenib
Cohort includes those with FLT3-ITD and -D835 mutated participants with relapsed/refractory AML, including participants who may have been previously exposed to one or more FLT3-inhibitors.
Phase I Starting Dose of Sorafenib: 400 mg by mouth twice daily for a 28 day cycle.
Phase I Starting Dose of Selinexor: 80 mg by mouth twice weekly for a 28 day cycle. Phase I Group 2 received Selinexor 80 mg by mouth twice weekly for a 28 day cycle.
|
Cohort 1 (FLT3-ITD Inhibitor Failure Cohort)
n=6 Participants
Cohort includes those with FLT3-ITD and -D835 mutated relapsed/refractory AML who have failed therapy with up to two prior salvage regimens.
Phase II Starting Dose of Sorafenib: Maximum tolerated dose combination from Phase I.
Phase II Starting Dose of Selinexor: Maximum tolerated dose from Phase I.
Selinexor: Phase I Starting Dose of Selinexor: 80 mg by mouth twice weekly for a 28 day cycle.
Phase II Starting Dose of Selinexor: Maximum tolerated dose from Phase I.
Sorafenib: Phase I Starting Dose of Sorafenib: 400 mg by mouth twice daily for a 28 day cycle.
Phase II Starting Dose of Sorafenib: Maximum tolerated dose combination from Phase I.
|
Cohort 2 (FLT3-ITD Inhibitor Naive Cohort)
n=2 Participants
Cohort includes those with FLT3-ITD and -D835 mutated relapsed/refractory AML who have failed therapy with up to two prior salvage regimens.
Phase II Starting Dose of Sorafenib: Maximum tolerated dose combination from Phase I.
Phase II Starting Dose of Selinexor: Maximum tolerated dose from Phase I.
Selinexor: Phase I Starting Dose of Selinexor: 80 mg by mouth twice weekly for a 28 day cycle.
Phase II Starting Dose of Selinexor: Maximum tolerated dose from Phase I.
Sorafenib: Phase I Starting Dose of Sorafenib: 400 mg by mouth twice daily for a 28 day cycle.
Phase II Starting Dose of Sorafenib: Maximum tolerated dose combination from Phase I.
|
|---|---|---|---|---|
|
Overall Survival
|
—
|
—
|
3.5 Months
Interval 0.9 to 14.0
|
2.3 Months
Interval 0.8 to 5.5
|
SECONDARY outcome
Timeframe: Up to 6 monthsPopulation: Event Free Survival was not an objective outlined for participants in Phase I Group's 1 and 2, therefore overall survival was not done for these participants. Of the seven participants in cohort 1, one participant was not evaluable for response. Of the three participants in cohort 2, one participant was not evaluable for response.
Time from date of treatment start until the date of first objective documentation of disease-relapse.
Outcome measures
| Measure |
Phase I Group 1 Selinexor + Sorafenib
Cohort includes those with FLT3-ITD and -D835 mutated participants with relapsed/refractory AML, including participants who may have been previously exposed to one or more FLT3-inhibitors.
Phase I Starting Dose of Sorafenib: 400 mg by mouth twice daily for a 28 day cycle.
Phase I Starting Dose of Selinexor: 80 mg by mouth twice weekly for a 28 day cycle.
Selinexor: Phase I Starting Dose of Selinexor: 80 mg by mouth twice weekly for a 28 day cycle.
Phase II Starting Dose of Selinexor: Maximum tolerated dose from Phase I.
Sorafenib: Phase I Starting Dose of Sorafenib: 400 mg by mouth twice daily for a 28 day cycle.
Phase II Starting Dose of Sorafenib: Maximum tolerated dose combination from Phase I.
|
Phase I Group 2 Selinexor + Sorafenib
Cohort includes those with FLT3-ITD and -D835 mutated participants with relapsed/refractory AML, including participants who may have been previously exposed to one or more FLT3-inhibitors.
Phase I Starting Dose of Sorafenib: 400 mg by mouth twice daily for a 28 day cycle.
Phase I Starting Dose of Selinexor: 80 mg by mouth twice weekly for a 28 day cycle. Phase I Group 2 received Selinexor 80 mg by mouth twice weekly for a 28 day cycle.
|
Cohort 1 (FLT3-ITD Inhibitor Failure Cohort)
n=6 Participants
Cohort includes those with FLT3-ITD and -D835 mutated relapsed/refractory AML who have failed therapy with up to two prior salvage regimens.
Phase II Starting Dose of Sorafenib: Maximum tolerated dose combination from Phase I.
Phase II Starting Dose of Selinexor: Maximum tolerated dose from Phase I.
Selinexor: Phase I Starting Dose of Selinexor: 80 mg by mouth twice weekly for a 28 day cycle.
Phase II Starting Dose of Selinexor: Maximum tolerated dose from Phase I.
Sorafenib: Phase I Starting Dose of Sorafenib: 400 mg by mouth twice daily for a 28 day cycle.
Phase II Starting Dose of Sorafenib: Maximum tolerated dose combination from Phase I.
|
Cohort 2 (FLT3-ITD Inhibitor Naive Cohort)
n=2 Participants
Cohort includes those with FLT3-ITD and -D835 mutated relapsed/refractory AML who have failed therapy with up to two prior salvage regimens.
Phase II Starting Dose of Sorafenib: Maximum tolerated dose combination from Phase I.
Phase II Starting Dose of Selinexor: Maximum tolerated dose from Phase I.
Selinexor: Phase I Starting Dose of Selinexor: 80 mg by mouth twice weekly for a 28 day cycle.
Phase II Starting Dose of Selinexor: Maximum tolerated dose from Phase I.
Sorafenib: Phase I Starting Dose of Sorafenib: 400 mg by mouth twice daily for a 28 day cycle.
Phase II Starting Dose of Sorafenib: Maximum tolerated dose combination from Phase I.
|
|---|---|---|---|---|
|
Event Free Survival
|
—
|
—
|
1.8 Months
Interval 0.4 to 5.0
|
2.1 Months
Interval 0.7 to 2.1
|
Adverse Events
Phase I Group 1 Selinexor + Sorafenib
Serious events: 4 serious events
Other events: 3 other events
Deaths: 1 deaths
Phase I Group 2 Selinexor + Sorafenib
Serious events: 3 serious events
Other events: 3 other events
Deaths: 0 deaths
Cohort 1 (FLT3-ITD Inhibitor Failure Cohort)
Serious events: 6 serious events
Other events: 6 other events
Deaths: 2 deaths
Cohort 2 (FLT3-ITD Inhibitor Naive Cohort)
Serious events: 3 serious events
Other events: 1 other events
Deaths: 2 deaths
Serious adverse events
| Measure |
Phase I Group 1 Selinexor + Sorafenib
n=4 participants at risk
Cohort includes those with FLT3-ITD and -D835 mutated participants with relapsed/refractory AML, including participants who may have been previously exposed to one or more FLT3-inhibitors.
Phase I Starting Dose of Sorafenib: 400 mg by mouth twice daily for a 28 day cycle.
Phase I Starting Dose of Selinexor: 80 mg by mouth twice weekly for a 28 day cycle.
Selinexor: Phase I Starting Dose of Selinexor: 80 mg by mouth twice weekly for a 28 day cycle.
Phase II Starting Dose of Selinexor: Maximum tolerated dose from Phase I.
Sorafenib: Phase I Starting Dose of Sorafenib: 400 mg by mouth twice daily for a 28 day cycle.
Phase II Starting Dose of Sorafenib: Maximum tolerated dose combination from Phase I.
|
Phase I Group 2 Selinexor + Sorafenib
n=3 participants at risk
Cohort includes those with FLT3-ITD and -D835 mutated participants with relapsed/refractory AML, including participants who may have been previously exposed to one or more FLT3-inhibitors.
Phase I Starting Dose of Sorafenib: 400 mg by mouth twice daily for a 28 day cycle.
Phase I Starting Dose of Selinexor: 80 mg by mouth twice weekly for a 28 day cycle. Phase I Group 2 received Selinexor 80 mg by mouth twice weekly for a 28 day cycle.
|
Cohort 1 (FLT3-ITD Inhibitor Failure Cohort)
n=7 participants at risk；n=6 participants at risk
Cohort includes those with FLT3-ITD and -D835 mutated relapsed/refractory AML who have failed therapy with up to two prior salvage regimens.
Phase II Starting Dose of Sorafenib: Maximum tolerated dose combination from Phase I.
Phase II Starting Dose of Selinexor: Maximum tolerated dose from Phase I.
Selinexor: Phase I Starting Dose of Selinexor: 80 mg by mouth twice weekly for a 28 day cycle.
Phase II Starting Dose of Selinexor: Maximum tolerated dose from Phase I.
Sorafenib: Phase I Starting Dose of Sorafenib: 400 mg by mouth twice daily for a 28 day cycle.
Phase II Starting Dose of Sorafenib: Maximum tolerated dose combination from Phase I.
|
Cohort 2 (FLT3-ITD Inhibitor Naive Cohort)
n=3 participants at risk
Cohort includes those with FLT3-ITD and -D835 mutated relapsed/refractory AML who have failed therapy with up to two prior salvage regimens.
Phase II Starting Dose of Sorafenib: Maximum tolerated dose combination from Phase I.
Phase II Starting Dose of Selinexor: Maximum tolerated dose from Phase I.
Selinexor: Phase I Starting Dose of Selinexor: 80 mg by mouth twice weekly for a 28 day cycle.
Phase II Starting Dose of Selinexor: Maximum tolerated dose from Phase I.
Sorafenib: Phase I Starting Dose of Sorafenib: 400 mg by mouth twice daily for a 28 day cycle.
Phase II Starting Dose of Sorafenib: Maximum tolerated dose combination from Phase I.
|
|---|---|---|---|---|
|
Renal and urinary disorders
Acute Kidney Injury
|
0.00%
0/4 • 2 years, 7 months
|
0.00%
0/3 • 2 years, 7 months
|
16.7%
1/6 • Number of events 1 • 2 years, 7 months
|
0.00%
0/3 • 2 years, 7 months
|
|
Respiratory, thoracic and mediastinal disorders
Bronchopulmonary Hemorrhage
|
0.00%
0/4 • 2 years, 7 months
|
0.00%
0/3 • 2 years, 7 months
|
16.7%
1/6 • Number of events 1 • 2 years, 7 months
|
0.00%
0/3 • 2 years, 7 months
|
|
Gastrointestinal disorders
Dehydration
|
0.00%
0/4 • 2 years, 7 months
|
0.00%
0/3 • 2 years, 7 months
|
16.7%
1/6 • Number of events 1 • 2 years, 7 months
|
0.00%
0/3 • 2 years, 7 months
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/4 • 2 years, 7 months
|
0.00%
0/3 • 2 years, 7 months
|
0.00%
0/6 • 2 years, 7 months
|
33.3%
1/3 • Number of events 1 • 2 years, 7 months
|
|
General disorders
Fatigue
|
0.00%
0/4 • 2 years, 7 months
|
33.3%
1/3 • Number of events 1 • 2 years, 7 months
|
16.7%
1/6 • Number of events 1 • 2 years, 7 months
|
0.00%
0/3 • 2 years, 7 months
|
|
Infections and infestations
Febrile Neutropenia
|
0.00%
0/4 • 2 years, 7 months
|
0.00%
0/3 • 2 years, 7 months
|
50.0%
3/6 • Number of events 5 • 2 years, 7 months
|
33.3%
1/3 • Number of events 1 • 2 years, 7 months
|
|
General disorders
Fever
|
0.00%
0/4 • 2 years, 7 months
|
0.00%
0/3 • 2 years, 7 months
|
0.00%
0/6 • 2 years, 7 months
|
33.3%
1/3 • Number of events 1 • 2 years, 7 months
|
|
Gastrointestinal disorders
Gastrointestinal Disorders Other
|
0.00%
0/4 • 2 years, 7 months
|
33.3%
1/3 • Number of events 1 • 2 years, 7 months
|
0.00%
0/6 • 2 years, 7 months
|
0.00%
0/3 • 2 years, 7 months
|
|
General disorders
Administration Site Conditions
|
0.00%
0/4 • 2 years, 7 months
|
33.3%
1/3 • Number of events 1 • 2 years, 7 months
|
0.00%
0/6 • 2 years, 7 months
|
0.00%
0/3 • 2 years, 7 months
|
|
Metabolism and nutrition disorders
Hyponatremia
|
0.00%
0/4 • 2 years, 7 months
|
0.00%
0/3 • 2 years, 7 months
|
0.00%
0/6 • 2 years, 7 months
|
33.3%
1/3 • Number of events 1 • 2 years, 7 months
|
|
Vascular disorders
Hypotension
|
25.0%
1/4 • Number of events 1 • 2 years, 7 months
|
0.00%
0/3 • 2 years, 7 months
|
0.00%
0/6 • 2 years, 7 months
|
0.00%
0/3 • 2 years, 7 months
|
|
Infections and infestations
Infections
|
25.0%
1/4 • Number of events 1 • 2 years, 7 months
|
0.00%
0/3 • 2 years, 7 months
|
16.7%
1/6 • Number of events 1 • 2 years, 7 months
|
66.7%
2/3 • Number of events 3 • 2 years, 7 months
|
|
Nervous system disorders
Intracranial Hemorrhage
|
0.00%
0/4 • 2 years, 7 months
|
33.3%
1/3 • Number of events 1 • 2 years, 7 months
|
16.7%
1/6 • Number of events 1 • 2 years, 7 months
|
0.00%
0/3 • 2 years, 7 months
|
|
Gastrointestinal disorders
Lower Gastrointestinal Hemorrhage
|
25.0%
1/4 • Number of events 1 • 2 years, 7 months
|
0.00%
0/3 • 2 years, 7 months
|
0.00%
0/6 • 2 years, 7 months
|
0.00%
0/3 • 2 years, 7 months
|
|
Infections and infestations
Lung Infection
|
0.00%
0/4 • 2 years, 7 months
|
66.7%
2/3 • Number of events 2 • 2 years, 7 months
|
16.7%
1/6 • Number of events 1 • 2 years, 7 months
|
0.00%
0/3 • 2 years, 7 months
|
|
Musculoskeletal and connective tissue disorders
Muscle Weakness Lower Limb
|
0.00%
0/4 • 2 years, 7 months
|
0.00%
0/3 • 2 years, 7 months
|
16.7%
1/6 • Number of events 1 • 2 years, 7 months
|
0.00%
0/3 • 2 years, 7 months
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/4 • 2 years, 7 months
|
0.00%
0/3 • 2 years, 7 months
|
16.7%
1/6 • Number of events 1 • 2 years, 7 months
|
0.00%
0/3 • 2 years, 7 months
|
|
General disorders
Neck Pain
|
25.0%
1/4 • Number of events 1 • 2 years, 7 months
|
0.00%
0/3 • 2 years, 7 months
|
0.00%
0/6 • 2 years, 7 months
|
0.00%
0/3 • 2 years, 7 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and Unspecified
|
0.00%
0/4 • 2 years, 7 months
|
100.0%
3/3 • Number of events 3 • 2 years, 7 months
|
16.7%
1/6 • Number of events 1 • 2 years, 7 months
|
0.00%
0/3 • 2 years, 7 months
|
|
Investigations
Thrombocytopenia
|
0.00%
0/4 • 2 years, 7 months
|
0.00%
0/3 • 2 years, 7 months
|
0.00%
0/6 • 2 years, 7 months
|
33.3%
1/3 • Number of events 3 • 2 years, 7 months
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary Edema
|
0.00%
0/4 • 2 years, 7 months
|
0.00%
0/3 • 2 years, 7 months
|
0.00%
0/6 • 2 years, 7 months
|
33.3%
1/3 • Number of events 1 • 2 years, 7 months
|
|
Gastrointestinal disorders
Rectal Hemorrhage
|
0.00%
0/4 • 2 years, 7 months
|
33.3%
1/3 • Number of events 1 • 2 years, 7 months
|
0.00%
0/6 • 2 years, 7 months
|
0.00%
0/3 • 2 years, 7 months
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory Failure
|
25.0%
1/4 • Number of events 1 • 2 years, 7 months
|
0.00%
0/3 • 2 years, 7 months
|
0.00%
0/6 • 2 years, 7 months
|
0.00%
0/3 • 2 years, 7 months
|
|
Nervous system disorders
Seizure
|
0.00%
0/4 • 2 years, 7 months
|
0.00%
0/3 • 2 years, 7 months
|
16.7%
1/6 • Number of events 1 • 2 years, 7 months
|
0.00%
0/3 • 2 years, 7 months
|
|
Infections and infestations
Sepsis
|
0.00%
0/4 • 2 years, 7 months
|
0.00%
0/3 • 2 years, 7 months
|
16.7%
1/6 • Number of events 1 • 2 years, 7 months
|
33.3%
1/3 • Number of events 1 • 2 years, 7 months
|
|
Nervous system disorders
Syncope
|
25.0%
1/4 • Number of events 1 • 2 years, 7 months
|
0.00%
0/3 • 2 years, 7 months
|
16.7%
1/6 • Number of events 2 • 2 years, 7 months
|
33.3%
1/3 • Number of events 1 • 2 years, 7 months
|
Other adverse events
| Measure |
Phase I Group 1 Selinexor + Sorafenib
n=4 participants at risk
Cohort includes those with FLT3-ITD and -D835 mutated participants with relapsed/refractory AML, including participants who may have been previously exposed to one or more FLT3-inhibitors.
Phase I Starting Dose of Sorafenib: 400 mg by mouth twice daily for a 28 day cycle.
Phase I Starting Dose of Selinexor: 80 mg by mouth twice weekly for a 28 day cycle.
Selinexor: Phase I Starting Dose of Selinexor: 80 mg by mouth twice weekly for a 28 day cycle.
Phase II Starting Dose of Selinexor: Maximum tolerated dose from Phase I.
Sorafenib: Phase I Starting Dose of Sorafenib: 400 mg by mouth twice daily for a 28 day cycle.
Phase II Starting Dose of Sorafenib: Maximum tolerated dose combination from Phase I.
|
Phase I Group 2 Selinexor + Sorafenib
n=3 participants at risk
Cohort includes those with FLT3-ITD and -D835 mutated participants with relapsed/refractory AML, including participants who may have been previously exposed to one or more FLT3-inhibitors.
Phase I Starting Dose of Sorafenib: 400 mg by mouth twice daily for a 28 day cycle.
Phase I Starting Dose of Selinexor: 80 mg by mouth twice weekly for a 28 day cycle. Phase I Group 2 received Selinexor 80 mg by mouth twice weekly for a 28 day cycle.
|
Cohort 1 (FLT3-ITD Inhibitor Failure Cohort)
n=7 participants at risk；n=6 participants at risk
Cohort includes those with FLT3-ITD and -D835 mutated relapsed/refractory AML who have failed therapy with up to two prior salvage regimens.
Phase II Starting Dose of Sorafenib: Maximum tolerated dose combination from Phase I.
Phase II Starting Dose of Selinexor: Maximum tolerated dose from Phase I.
Selinexor: Phase I Starting Dose of Selinexor: 80 mg by mouth twice weekly for a 28 day cycle.
Phase II Starting Dose of Selinexor: Maximum tolerated dose from Phase I.
Sorafenib: Phase I Starting Dose of Sorafenib: 400 mg by mouth twice daily for a 28 day cycle.
Phase II Starting Dose of Sorafenib: Maximum tolerated dose combination from Phase I.
|
Cohort 2 (FLT3-ITD Inhibitor Naive Cohort)
n=3 participants at risk
Cohort includes those with FLT3-ITD and -D835 mutated relapsed/refractory AML who have failed therapy with up to two prior salvage regimens.
Phase II Starting Dose of Sorafenib: Maximum tolerated dose combination from Phase I.
Phase II Starting Dose of Selinexor: Maximum tolerated dose from Phase I.
Selinexor: Phase I Starting Dose of Selinexor: 80 mg by mouth twice weekly for a 28 day cycle.
Phase II Starting Dose of Selinexor: Maximum tolerated dose from Phase I.
Sorafenib: Phase I Starting Dose of Sorafenib: 400 mg by mouth twice daily for a 28 day cycle.
Phase II Starting Dose of Sorafenib: Maximum tolerated dose combination from Phase I.
|
|---|---|---|---|---|
|
Renal and urinary disorders
Acute Kidney Injury
|
0.00%
0/4 • 2 years, 7 months
|
0.00%
0/3 • 2 years, 7 months
|
14.3%
1/7 • Number of events 1 • 2 years, 7 months
|
0.00%
0/3 • 2 years, 7 months
|
|
Endocrine disorders
Adrenal insufficiency
|
25.0%
1/4 • Number of events 2 • 2 years, 7 months
|
0.00%
0/3 • 2 years, 7 months
|
0.00%
0/7 • 2 years, 7 months
|
0.00%
0/3 • 2 years, 7 months
|
|
Metabolism and nutrition disorders
Anorexia
|
75.0%
3/4 • Number of events 6 • 2 years, 7 months
|
100.0%
3/3 • Number of events 4 • 2 years, 7 months
|
42.9%
3/7 • Number of events 4 • 2 years, 7 months
|
33.3%
1/3 • Number of events 1 • 2 years, 7 months
|
|
Cardiac disorders
Cardiac Disorders
|
50.0%
2/4 • Number of events 3 • 2 years, 7 months
|
33.3%
1/3 • Number of events 1 • 2 years, 7 months
|
0.00%
0/7 • 2 years, 7 months
|
0.00%
0/3 • 2 years, 7 months
|
|
Psychiatric disorders
Confusion
|
0.00%
0/4 • 2 years, 7 months
|
33.3%
1/3 • Number of events 1 • 2 years, 7 months
|
14.3%
1/7 • Number of events 1 • 2 years, 7 months
|
0.00%
0/3 • 2 years, 7 months
|
|
Gastrointestinal disorders
Diarrhea
|
50.0%
2/4 • Number of events 3 • 2 years, 7 months
|
66.7%
2/3 • Number of events 3 • 2 years, 7 months
|
42.9%
3/7 • Number of events 5 • 2 years, 7 months
|
33.3%
1/3 • Number of events 3 • 2 years, 7 months
|
|
General disorders
Fatigue
|
75.0%
3/4 • Number of events 4 • 2 years, 7 months
|
66.7%
2/3 • Number of events 4 • 2 years, 7 months
|
42.9%
3/7 • Number of events 5 • 2 years, 7 months
|
33.3%
1/3 • Number of events 1 • 2 years, 7 months
|
|
Investigations
Hyperbilirubinemia
|
25.0%
1/4 • Number of events 1 • 2 years, 7 months
|
0.00%
0/3 • 2 years, 7 months
|
14.3%
1/7 • Number of events 1 • 2 years, 7 months
|
0.00%
0/3 • 2 years, 7 months
|
|
Metabolism and nutrition disorders
Hyponatremia
|
50.0%
2/4 • Number of events 2 • 2 years, 7 months
|
33.3%
1/3 • Number of events 2 • 2 years, 7 months
|
42.9%
3/7 • Number of events 5 • 2 years, 7 months
|
33.3%
1/3 • Number of events 2 • 2 years, 7 months
|
|
Infections and infestations
Infection Other
|
25.0%
1/4 • Number of events 1 • 2 years, 7 months
|
0.00%
0/3 • 2 years, 7 months
|
28.6%
2/7 • Number of events 4 • 2 years, 7 months
|
0.00%
0/3 • 2 years, 7 months
|
|
Gastrointestinal disorders
Nausea/Vomiting
|
75.0%
3/4 • Number of events 6 • 2 years, 7 months
|
33.3%
1/3 • Number of events 1 • 2 years, 7 months
|
42.9%
3/7 • Number of events 3 • 2 years, 7 months
|
33.3%
1/3 • Number of events 1 • 2 years, 7 months
|
|
Musculoskeletal and connective tissue disorders
Weakness
|
75.0%
3/4 • Number of events 4 • 2 years, 7 months
|
0.00%
0/3 • 2 years, 7 months
|
28.6%
2/7 • Number of events 2 • 2 years, 7 months
|
0.00%
0/3 • 2 years, 7 months
|
|
Investigations
Weight Loss
|
50.0%
2/4 • Number of events 2 • 2 years, 7 months
|
66.7%
2/3 • Number of events 2 • 2 years, 7 months
|
42.9%
3/7 • Number of events 4 • 2 years, 7 months
|
0.00%
0/3 • 2 years, 7 months
|
Additional Information
Naval Daver, MD/Associate Professor
The University of Texas MD Anderson Cancer Center
Phone: 713-794-4392
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place