Trial Outcomes & Findings for Trametinib and Akt Inhibitor GSK2141795 in Treating Patients With Acute Myeloid Leukemia (NCT NCT01907815)

NCT ID: NCT01907815

Last Updated: 2018-04-06

Results Overview

Proportion of participants achieving complete remission (CR) or CR with incomplete recovery of platelets (CRp) as best response within 4 cycles of therapy. Complete Response (CR): Disappearance all clinical \&/or radiologic evidence of disease. Neutrophil count ≥ 1.0x10\^9/L; Platelet count ≥ 100x109/L; Normal bone marrow differential (≤ 5% blasts); No extra-medullary leukemia. Complete Remission without Platelet Recovery (CRp): Peripheral blood \& bone marrow results as for CR, but platelet counts of \< 100x10\^9/L. Partial Remission (PR): Blood count recovery as for CR, but decrease of at least 50% in % marrow blasts to \>5% to 25% in bone marrow aspirate. Morphologic leukemia-free state: Normal marrow differential (\<5% blasts); neutrophil \& platelet counts not considered.95% confidence interval will be estimated for the combination regimen.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

24 participants

Primary outcome timeframe

First four cycles (16 weeks) of therapy, with evaluation after one full cycle of therapy (28 days) and up to 16 weeks for response

Results posted on

2018-04-06

Participant Flow

Recruitment Period: October 9, 2013 to January 25, 2016. All recruitment done within medical clinic settings at The University of Texas MD Anderson Cancer Center, The University of Chicago and The University of Maryland Greenebaum Cancer Center.

Study was terminated early, stopped due to lack of efficacy.

Participant milestones

Participant milestones
Measure	Trametinib 2.0 mg + GSK2141795 25 mg Trametinib 2.0 mg orally once daily (PO QD) and Akt inhibitor GSK2141795 25 mg PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity	Trametinib 1.5 mg + GSK2141795 50 mg Trametinib 1.5 mg PO QD + GSK2141795 50 mg PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity
Overall Study STARTED	17	7
Overall Study COMPLETED	16	7
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Trametinib 2.0 mg + GSK2141795 25 mg Trametinib 2.0 mg orally once daily (PO QD) and Akt inhibitor GSK2141795 25 mg PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity	Trametinib 1.5 mg + GSK2141795 50 mg Trametinib 1.5 mg PO QD + GSK2141795 50 mg PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity
Overall Study Withdrawal by Subject	1	0

Baseline Characteristics

Trametinib and Akt Inhibitor GSK2141795 in Treating Patients With Acute Myeloid Leukemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Trametinib 2.0 mg + GSK2141795 25 mg n=17 Participants Trametinib 2.0 mg PO QD + GSK2141795 25 mg PO QD on days 1-28.	Trametinib 1.5 mg + GSK2141795 50 mg n=7 Participants Trametinib 1.5 mg PO QD + GSK2141795 50 mg PO QD on days 1-28.	Total n=24 Participants Total of all reporting groups
Age, Continuous	68 years n=5 Participants	69 years n=7 Participants	69 years n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	3 Participants n=7 Participants	9 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	4 Participants n=7 Participants	15 Participants n=5 Participants
Region of Enrollment United States	17 Participants n=5 Participants	7 Participants n=7 Participants	24 Participants n=5 Participants

PRIMARY outcome

Timeframe: First four cycles (16 weeks) of therapy, with evaluation after one full cycle of therapy (28 days) and up to 16 weeks for response

Population: One participant in first cohort withdrew prior to treatment therefore excluded from study analysis.

Outcome measures

Outcome measures
Measure	Trametinib 2.0 mg + GSK2141795 25 mg n=16 Participants Trametinib 2.0 mg PO QD \& GSK2141795 25 mg PO QD on days 1-28.	Trametinib 1.5 mg + GSK2141795 50 mg n=7 Participants Trametinib 1.5 mg PO QD + GSK2141795 50 mg PO QD on days 1-28.
Complete Response Rate (CRR, Defined as CR+CRp) Assessed by AML 2003 Response Criteria	0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: AE collected continuously over 28-day cycles and up to 28 days after last dose of study drug.

Population: One participant of the 17 registered in first cohort (Trametinib 2.0) withdrew without treatment and is excluded from adverse event reporting.

National Cancer Institute (NCI) published standardized definitions for adverse events (AEs), known as Common Terminology Criteria for Adverse Events (CTCAE), to describe the severity of organ toxicity for those receiving cancer therapy. Toxicity data is summarized by number of incidents experienced while participants were on study using most frequently reported AEs regardless of grade or relatedness as assessed by CTCAE version 4.0. Toxicity is graded as mild (Grade 1), moderate (Grade 2), severe (Grade 3), or life-threatening (Grade 4), with specific parameters according to the organ system involved. Death (Grade 5) is used for some of the criteria to denote a fatality. For full adverse event reporting see Adverse Event Section. Data collection over first four cycles (16 weeks) of therapy, with evaluation after full cycle of therapy (28 days), continuing AE collection until 28 days following last study drug dose.

Outcome measures

Outcome measures
Measure	Trametinib 2.0 mg + GSK2141795 25 mg n=16 Participants Trametinib 2.0 mg PO QD \& GSK2141795 25 mg PO QD on days 1-28.	Trametinib 1.5 mg + GSK2141795 50 mg n=7 Participants Trametinib 1.5 mg PO QD + GSK2141795 50 mg PO QD on days 1-28.
Most Frequently Reported Adverse Events (AE) Anemia	15 events	3 events
Most Frequently Reported Adverse Events (AE) Diarrhea	16 events	3 events
Most Frequently Reported Adverse Events (AE) Fatigue	11 events	6 events
Most Frequently Reported Adverse Events (AE) Fever	13 events	3 events
Most Frequently Reported Adverse Events (AE) Nausea	8 events	3 events
Most Frequently Reported Adverse Events (AE) Rash maculo-papular	6 events	5 events
Most Frequently Reported Adverse Events (AE) Mucositis oral	5 events	3 events
Most Frequently Reported Adverse Events (AE) Vomiting	7 events	1 events

SECONDARY outcome

Timeframe: Up to 12 weeks

Population: No participants achieved CR/CRp therefore analysis not available.

Estimated using the Kaplan-Meier method. Log-rank test will be performed to test the difference in time-to-event distributions between patient groups. Cox proportional hazards model will be used to include multiple covariates in the time-to-event analysis.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 12 weeks

Population: No participants achieved CR/CRp therefore analysis not available.

Estimated disease-free survival period using the Kaplan-Meier method. Log-rank test will be performed to test the difference in time-to-event distributions between patient groups. Cox proportional hazards model will be used to include multiple covariates in the time-to-event analysis.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 12 weeks

Population: Outcome data were not collected and the Outcome will never be analyzed.

Time to Progression (TTP) is defined as the length of time from the start of treatment to disease progression as measured in days for participants with complete response.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to 12 weeks post therapy

Change in total and phospho-proteins assessed by densitometric quantitative data by western blot analysis, or mean fluorescent intensities by flow cytometry and will be assessed for each patient for all time points and graphically plotted for each dose level.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to day 28 post treatment

The 95% confidence interval will be assessed.

Outcome measures

Outcome data not reported

Adverse Events

Trametinib 2.0 mg + GSK2141795 25 mg

Serious events: 11 serious events

Other events: 16 other events

Deaths: 0 deaths

Trametinib 1.5 mg + GSK2141795 50 mg

Serious events: 6 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Nitin Jain, MD, Assistant Professor, Leukemia

The University of Texas MD Anderson Cancer Center

Phone: 713-792-7734

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Trametinib 2.0 mg + GSK2141795 25 mg n=16 participants at risk Trametinib 2.0 mg PO QD + GSK2141795 25 mg PO QD on days 1-28.	Trametinib 1.5 mg + GSK2141795 50 mg n=7 participants at risk Trametinib 1.5 mg PO QD + GSK2141795 50 mg PO QD on days 1-28.
Investigations Alanine aminotransferase increased	6.2% 1/16 • Number of events 1 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.	0.00% 0/7 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.
Investigations Alkaline phosphatase increased	6.2% 1/16 • Number of events 1 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.	0.00% 0/7 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.
Cardiac disorders Atrial fibrillation	0.00% 0/16 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.	14.3% 1/7 • Number of events 1 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.
Respiratory, thoracic and mediastinal disorders Bronchial infection	0.00% 0/16 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.	14.3% 1/7 • Number of events 1 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.
Respiratory, thoracic and mediastinal disorders Bronchopulmonary hemorrhage	0.00% 0/16 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.	14.3% 1/7 • Number of events 1 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.
Cardiac disorders Carotid Stent placed	6.2% 1/16 • Number of events 1 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.	0.00% 0/7 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.
Infections and infestations Catheter related infection	0.00% 0/16 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.	14.3% 1/7 • Number of events 1 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.
Psychiatric disorders Confusion	6.2% 1/16 • Number of events 1 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.	0.00% 0/7 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.
Investigations Creatinine increased	0.00% 0/16 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.	14.3% 1/7 • Number of events 1 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.
General disorders Death NOS	18.8% 3/16 • Number of events 3 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.	0.00% 0/7 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.
Metabolism and nutrition disorders Dehydration	6.2% 1/16 • Number of events 1 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.	14.3% 1/7 • Number of events 1 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.
Gastrointestinal disorders Diarrhea	12.5% 2/16 • Number of events 2 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.	0.00% 0/7 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.
Reproductive system and breast disorders Dyspnea	12.5% 2/16 • Number of events 2 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.	14.3% 1/7 • Number of events 1 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.
Investigations Ejection fraction decreased	6.2% 1/16 • Number of events 1 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.	14.3% 1/7 • Number of events 1 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.
Injury, poisoning and procedural complications Fall	6.2% 1/16 • Number of events 1 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.	0.00% 0/7 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.
Blood and lymphatic system disorders Febrile neutropenia	6.2% 1/16 • Number of events 2 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.	14.3% 1/7 • Number of events 1 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.
General disorders Fever	12.5% 2/16 • Number of events 5 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.	0.00% 0/7 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.
Gastrointestinal disorders Gastric hemorrhage	6.2% 1/16 • Number of events 1 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.	0.00% 0/7 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.
Gastrointestinal disorders Gastric perforation	0.00% 0/16 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.	14.3% 1/7 • Number of events 1 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.
Vascular disorders Hypotension	18.8% 3/16 • Number of events 4 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.	0.00% 0/7 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.
Blood and lymphatic system disorders Leukocytosis	6.2% 1/16 • Number of events 1 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.	0.00% 0/7 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.
Gastrointestinal disorders Lower gastrointestinal hemorrhage Gastric Ulcer	0.00% 0/16 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.	14.3% 1/7 • Number of events 1 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.
Infections and infestations Lung infection	6.2% 1/16 • Number of events 1 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.	0.00% 0/7 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.
Gastrointestinal disorders Mucositis oral	0.00% 0/16 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.	14.3% 1/7 • Number of events 1 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.
Cardiac disorders Myocardial infarction	6.2% 1/16 • Number of events 1 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.	0.00% 0/7 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.
Gastrointestinal disorders Nausea	6.2% 1/16 • Number of events 1 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.	0.00% 0/7 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/16 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.	14.3% 1/7 • Number of events 1 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.
Gastrointestinal disorders Rectal pain	6.2% 1/16 • Number of events 1 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.	0.00% 0/7 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.
Infections and infestations Sepsis	6.2% 1/16 • Number of events 1 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.	28.6% 2/7 • Number of events 2 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.
Skin and subcutaneous tissue disorders Skin infection	6.2% 1/16 • Number of events 1 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.	0.00% 0/7 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.
Nervous system disorders Syncope	6.2% 1/16 • Number of events 1 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.	0.00% 0/7 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.
Metabolism and nutrition disorders Tumor lysis syndrome	0.00% 0/16 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.	14.3% 1/7 • Number of events 1 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.
Gastrointestinal disorders Vomiting	6.2% 1/16 • Number of events 1 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.	0.00% 0/7 • Adverse events collected continuously over a 28-day cycle schedule and up to 28 days after last dose of study drug. One participant in first cohort withdrew prior to treatment therefore excluded from all study analysis.