Trial Outcomes & Findings for MEK Inhibitor 162 Relapsed and/or Refractory Acute Myeloid Leukemia (AML) and Poor Prognosis, Not Suitable for or Unwilling to Receive Standard Therapy (NCT NCT02089230)

NCT ID: NCT02089230

Last Updated: 2021-04-20

Results Overview

Maximum tolerated dose is the highest dose level in which \<2 patients of 6 develop dose limiting toxicity (DLT).

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

19 participants

Primary outcome timeframe

28 days

Results posted on

2021-04-20

Participant Flow

Recruitment Period: 9/2014 to 9/2017

Participant milestones

Participant milestones
Measure	Phase I Cohort 1 - MEK 162 Phase I Starting Dose of MEK 162: 30 mg by mouth twice a day in a 28 day cycle.	Phase I Cohort 2 - MEK 162 Phase I Starting Dose of MEK 162: 45 mg by mouth twice a day in a 28 day cycle.	Phase II Cohort 3 - MDK 162 Phase II Starting Dose of MEK 162: 45 mg by mouth twice a day in a 28 day cycle.
Overall Study STARTED	3	4	12
Overall Study COMPLETED	3	4	6
Overall Study NOT COMPLETED	0	0	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase I Cohort 1 - MEK 162 Phase I Starting Dose of MEK 162: 30 mg by mouth twice a day in a 28 day cycle.	Phase I Cohort 2 - MEK 162 Phase I Starting Dose of MEK 162: 45 mg by mouth twice a day in a 28 day cycle.	Phase II Cohort 3 - MDK 162 Phase II Starting Dose of MEK 162: 45 mg by mouth twice a day in a 28 day cycle.
Overall Study Death	0	0	2
Overall Study Seeking Alternative Therapy	0	0	4

Baseline Characteristics

MEK Inhibitor 162 Relapsed and/or Refractory Acute Myeloid Leukemia (AML) and Poor Prognosis, Not Suitable for or Unwilling to Receive Standard Therapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase I Cohort 1 - MEK 162 n=3 Participants Phase I Starting Dose of MEK 162: 30 mg by mouth twice a day in a 28 day cycle.	Phase I Cohort 2 - MEK 162 n=4 Participants Phase I Starting Dose of MEK 162: 45 mg by mouth twice a day in a 28 day cycle.	Phase II Cohort 3 - MDK 162 n=12 Participants Phase II Starting Dose of MEK 162: 45 mg by mouth twice a day in a 28 day cycle.	Total n=19 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
Age, Categorical Between 18 and 65 years	2 Participants n=5 Participants	2 Participants n=7 Participants	7 Participants n=5 Participants	11 Participants n=4 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants	8 Participants n=4 Participants
Age, Continuous	57 years n=5 Participants	63 years n=7 Participants	64.5 years n=5 Participants	64 years n=4 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	7 Participants n=4 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	2 Participants n=7 Participants	9 Participants n=5 Participants	12 Participants n=4 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
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 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
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants	15 Participants n=4 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
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment United States	3 participants n=5 Participants	4 participants n=7 Participants	12 participants n=5 Participants	19 participants n=4 Participants

PRIMARY outcome

Timeframe: 28 days

Population: Maximum Tolerated Dose (MTD) was not done for the Phase II portion of the study, therefore 0 participants in the Phase II portion of the study were analyzed.

Maximum tolerated dose is the highest dose level in which \<2 patients of 6 develop dose limiting toxicity (DLT).

Outcome measures

Outcome measures
Measure	Phase I Cohort 1 - MEK 162 n=3 Participants Phase I Starting Dose of MEK 162: 30 mg by mouth twice a day in a 28 day cycle.	Phase I Cohort 2 - MEK 162 n=4 Participants Phase I Starting Dose of MEK 162: 45 mg by mouth twice a day in a 28 day cycle.	Phase II Cohort 3 - MDK 162 Phase II Starting Dose of MEK 162: 45 mg by mouth twice a day in a 28 day cycle.
Maximum Tolerated Dose (MTD) of MEK 162 in Participants With Advanced Leukemias	NA Milligrams (mg) The MTD was not determined until cohort 2 of this study	45 Milligrams (mg)	—

SECONDARY outcome

Timeframe: Assessed after one 28-day cycle of treatment

Population: Six participants in Phase II Cohort 3 were not evlauable for response.

Response is Complete Remission (CR) or CR with incomplete blood count recovery (CRi) according to International Working Group (IWG) consensus criteria for treatment response in Acute Myeloid Leukemia (AML) (modified): Morphological Complete Remission (CR): Normalization of the peripheral blood absolute neutrophil count \> 1.0x109/L, platelets \> than 100x109/L no residual evidence of extramedullary disease and bone marrow aspirate with ≤ 5% blasts, no blasts with Auer rods (AML only); and Morphological Complete Remission with incomplete blood count recovery (CRi): Same as CR but without normalization of the peripheral blood absolute neutrophil and platelet count.

Outcome measures

Outcome measures
Measure	Phase I Cohort 1 - MEK 162 n=3 Participants Phase I Starting Dose of MEK 162: 30 mg by mouth twice a day in a 28 day cycle.	Phase I Cohort 2 - MEK 162 n=4 Participants Phase I Starting Dose of MEK 162: 45 mg by mouth twice a day in a 28 day cycle.	Phase II Cohort 3 - MDK 162 n=6 Participants Phase II Starting Dose of MEK 162: 45 mg by mouth twice a day in a 28 day cycle.
Number of Participants With a Response	0 participants	0 participants	1 participants

Adverse Events

Phase I Cohort 1 - MEK 162

Serious events: 3 serious events

Other events: 3 other events

Deaths: 2 deaths

Phase I Cohort 2 - MEK 162

Serious events: 3 serious events

Other events: 4 other events

Deaths: 1 deaths

Phase II Cohort 3 - MDK 162

Serious events: 10 serious events

Other events: 7 other events

Deaths: 8 deaths

Serious adverse events

Serious adverse events
Measure	Phase I Cohort 1 - MEK 162 n=3 participants at risk Phase I Starting Dose of MEK 162: 30 mg by mouth twice a day in a 28 day cycle.	Phase I Cohort 2 - MEK 162 n=4 participants at risk Phase I Starting Dose of MEK 162: 45 mg by mouth twice a day in a 28 day cycle.	Phase II Cohort 3 - MDK 162 n=12 participants at risk Phase II Starting Dose of MEK 162: 45 mg by mouth twice a day in a 28 day cycle.
Gastrointestinal disorders Abdominal Pain	0.00% 0/3 • Up to 3 years	0.00% 0/4 • Up to 3 years	16.7% 2/12 • Number of events 2 • Up to 3 years
Gastrointestinal disorders Anal Pain	0.00% 0/3 • Up to 3 years	25.0% 1/4 • Number of events 1 • Up to 3 years	0.00% 0/12 • Up to 3 years
Cardiac disorders Atrial Fibrillation	0.00% 0/3 • Up to 3 years	0.00% 0/4 • Up to 3 years	8.3% 1/12 • Number of events 1 • Up to 3 years
Blood and lymphatic system disorders Blood and Lymphatic System Disorders	0.00% 0/3 • Up to 3 years	0.00% 0/4 • Up to 3 years	8.3% 1/12 • Number of events 1 • Up to 3 years
Hepatobiliary disorders Cholecystitis	0.00% 0/3 • Up to 3 years	0.00% 0/4 • Up to 3 years	8.3% 1/12 • Number of events 1 • Up to 3 years
General disorders Progressive Disease	0.00% 0/3 • Up to 3 years	0.00% 0/4 • Up to 3 years	8.3% 1/12 • Number of events 1 • Up to 3 years
Blood and lymphatic system disorders Febrile Neutropenia	33.3% 1/3 • Number of events 1 • Up to 3 years	50.0% 2/4 • Number of events 2 • Up to 3 years	25.0% 3/12 • Number of events 5 • Up to 3 years
General disorders Fever	0.00% 0/3 • Up to 3 years	0.00% 0/4 • Up to 3 years	8.3% 1/12 • Number of events 1 • Up to 3 years
Vascular disorders Hypotension	33.3% 1/3 • Number of events 5 • Up to 3 years	0.00% 0/4 • Up to 3 years	16.7% 2/12 • Number of events 2 • Up to 3 years
Infections and infestations Infection	0.00% 0/3 • Up to 3 years	0.00% 0/4 • Up to 3 years	8.3% 1/12 • Number of events 1 • Up to 3 years
Blood and lymphatic system disorders Leukocytosis	0.00% 0/3 • Up to 3 years	0.00% 0/4 • Up to 3 years	8.3% 1/12 • Number of events 1 • Up to 3 years
Gastrointestinal disorders Lower Gastrointestinal Hemorrhage	0.00% 0/3 • Up to 3 years	0.00% 0/4 • Up to 3 years	8.3% 1/12 • Number of events 2 • Up to 3 years
Infections and infestations Lung Infection	100.0% 3/3 • Number of events 3 • Up to 3 years	0.00% 0/4 • Up to 3 years	16.7% 2/12 • Number of events 2 • Up to 3 years
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms Benign, Malignant and Unspecified	0.00% 0/3 • Up to 3 years	0.00% 0/4 • Up to 3 years	16.7% 2/12 • Number of events 2 • Up to 3 years
Respiratory, thoracic and mediastinal disorders Pleural Effusion	0.00% 0/3 • Up to 3 years	0.00% 0/4 • Up to 3 years	8.3% 1/12 • Number of events 1 • Up to 3 years
Respiratory, thoracic and mediastinal disorders Respiratory Failure	0.00% 0/3 • Up to 3 years	25.0% 1/4 • Number of events 1 • Up to 3 years	8.3% 1/12 • Number of events 1 • Up to 3 years
Infections and infestations Sepsis	0.00% 0/3 • Up to 3 years	0.00% 0/4 • Up to 3 years	8.3% 1/12 • Number of events 1 • Up to 3 years
Metabolism and nutrition disorders Tumor Lysis Syndrome	0.00% 0/3 • Up to 3 years	0.00% 0/4 • Up to 3 years	8.3% 1/12 • Number of events 1 • Up to 3 years
Gastrointestinal disorders Vomiting	33.3% 1/3 • Number of events 1 • Up to 3 years	0.00% 0/4 • Up to 3 years	0.00% 0/12 • Up to 3 years

Other adverse events

Other adverse events
Measure	Phase I Cohort 1 - MEK 162 n=3 participants at risk Phase I Starting Dose of MEK 162: 30 mg by mouth twice a day in a 28 day cycle.	Phase I Cohort 2 - MEK 162 n=4 participants at risk Phase I Starting Dose of MEK 162: 45 mg by mouth twice a day in a 28 day cycle.	Phase II Cohort 3 - MDK 162 n=12 participants at risk Phase II Starting Dose of MEK 162: 45 mg by mouth twice a day in a 28 day cycle.
Gastrointestinal disorders Abdominal Distension	33.3% 1/3 • Number of events 1 • Up to 3 years	0.00% 0/4 • Up to 3 years	0.00% 0/12 • Up to 3 years
Gastrointestinal disorders Abdominal Pain	66.7% 2/3 • Number of events 2 • Up to 3 years	25.0% 1/4 • Number of events 1 • Up to 3 years	8.3% 1/12 • Number of events 1 • Up to 3 years
Metabolism and nutrition disorders Acidosis	33.3% 1/3 • Number of events 1 • Up to 3 years	25.0% 1/4 • Number of events 1 • Up to 3 years	0.00% 0/12 • Up to 3 years
Renal and urinary disorders Acute Kidney Injury	0.00% 0/3 • Up to 3 years	0.00% 0/4 • Up to 3 years	16.7% 2/12 • Number of events 2 • Up to 3 years
Psychiatric disorders Agitation	33.3% 1/3 • Number of events 1 • Up to 3 years	0.00% 0/4 • Up to 3 years	0.00% 0/12 • Up to 3 years
Investigations Alanine Aminotransferase Increased	0.00% 0/3 • Up to 3 years	25.0% 1/4 • Number of events 1 • Up to 3 years	0.00% 0/12 • Up to 3 years
Investigations Alkaline Phosphatase Increase	66.7% 2/3 • Number of events 2 • Up to 3 years	75.0% 3/4 • Number of events 3 • Up to 3 years	0.00% 0/12 • Up to 3 years
Blood and lymphatic system disorders Anemia	0.00% 0/3 • Up to 3 years	25.0% 1/4 • Number of events 1 • Up to 3 years	0.00% 0/12 • Up to 3 years
Gastrointestinal disorders Anorexia	100.0% 3/3 • Number of events 3 • Up to 3 years	0.00% 0/4 • Up to 3 years	0.00% 0/12 • Up to 3 years
Psychiatric disorders Anxiety	66.7% 2/3 • Number of events 2 • Up to 3 years	25.0% 1/4 • Number of events 1 • Up to 3 years	0.00% 0/12 • Up to 3 years
Investigations Aspartate Aminotransferase Increased	33.3% 1/3 • Number of events 1 • Up to 3 years	100.0% 4/4 • Number of events 4 • Up to 3 years	0.00% 0/12 • Up to 3 years
Investigations Blood Bilirubin Increased	100.0% 3/3 • Number of events 3 • Up to 3 years	0.00% 0/4 • Up to 3 years	0.00% 0/12 • Up to 3 years
Gastrointestinal disorders Constipation	33.3% 1/3 • Number of events 1 • Up to 3 years	25.0% 1/4 • Number of events 1 • Up to 3 years	8.3% 1/12 • Number of events 1 • Up to 3 years
Respiratory, thoracic and mediastinal disorders Cough	100.0% 3/3 • Number of events 3 • Up to 3 years	0.00% 0/4 • Up to 3 years	8.3% 1/12 • Number of events 1 • Up to 3 years
Gastrointestinal disorders Diarrhea	100.0% 3/3 • Number of events 3 • Up to 3 years	75.0% 3/4 • Number of events 3 • Up to 3 years	8.3% 1/12 • Number of events 1 • Up to 3 years
Respiratory, thoracic and mediastinal disorders Dyspnea	100.0% 3/3 • Number of events 4 • Up to 3 years	25.0% 1/4 • Number of events 1 • Up to 3 years	0.00% 0/12 • Up to 3 years
General disorders Edema Limbs	100.0% 3/3 • Number of events 3 • Up to 3 years	25.0% 1/4 • Number of events 1 • Up to 3 years	0.00% 0/12 • Up to 3 years
Respiratory, thoracic and mediastinal disorders Epistaxis	66.7% 2/3 • Number of events 2 • Up to 3 years	25.0% 1/4 • Number of events 1 • Up to 3 years	0.00% 0/12 • Up to 3 years
Eye disorders Eye Disorders	66.7% 2/3 • Number of events 4 • Up to 3 years	50.0% 2/4 • Number of events 2 • Up to 3 years	8.3% 1/12 • Number of events 1 • Up to 3 years
General disorders Fatigue	100.0% 3/3 • Number of events 3 • Up to 3 years	50.0% 2/4 • Number of events 2 • Up to 3 years	0.00% 0/12 • Up to 3 years
Blood and lymphatic system disorders Neutropenic Fever	33.3% 1/3 • Number of events 1 • Up to 3 years	25.0% 1/4 • Number of events 1 • Up to 3 years	8.3% 1/12 • Number of events 1 • Up to 3 years
Metabolism and nutrition disorders Hyperglycemia	66.7% 2/3 • Number of events 2 • Up to 3 years	50.0% 2/4 • Number of events 2 • Up to 3 years	0.00% 0/12 • Up to 3 years
Metabolism and nutrition disorders Hyperkalemia	33.3% 1/3 • Number of events 1 • Up to 3 years	50.0% 2/4 • Number of events 2 • Up to 3 years	8.3% 1/12 • Number of events 1 • Up to 3 years
Metabolism and nutrition disorders Hypernatremia	66.7% 2/3 • Number of events 2 • Up to 3 years	25.0% 1/4 • Number of events 1 • Up to 3 years	0.00% 0/12 • Up to 3 years
Metabolism and nutrition disorders Hyperuricemia	33.3% 1/3 • Number of events 1 • Up to 3 years	25.0% 1/4 • Number of events 1 • Up to 3 years	0.00% 0/12 • Up to 3 years
Metabolism and nutrition disorders Hypoalbuminemia	100.0% 3/3 • Number of events 3 • Up to 3 years	50.0% 2/4 • Number of events 2 • Up to 3 years	0.00% 0/12 • Up to 3 years
Metabolism and nutrition disorders Hypocalcemia	100.0% 3/3 • Number of events 3 • Up to 3 years	50.0% 2/4 • Number of events 2 • Up to 3 years	0.00% 0/12 • Up to 3 years
Metabolism and nutrition disorders Hypokalemia	100.0% 3/3 • Number of events 3 • Up to 3 years	0.00% 0/4 • Up to 3 years	16.7% 2/12 • Number of events 2 • Up to 3 years
Metabolism and nutrition disorders Hypomagnesemia	66.7% 2/3 • Number of events 2 • Up to 3 years	50.0% 2/4 • Number of events 2 • Up to 3 years	8.3% 1/12 • Number of events 1 • Up to 3 years
Metabolism and nutrition disorders Hyponatremia	66.7% 2/3 • Number of events 2 • Up to 3 years	50.0% 2/4 • Number of events 2 • Up to 3 years	8.3% 1/12 • Number of events 1 • Up to 3 years
Vascular disorders Hypotension	33.3% 1/3 • Number of events 1 • Up to 3 years	25.0% 1/4 • Number of events 1 • Up to 3 years	8.3% 1/12 • Number of events 1 • Up to 3 years
Infections and infestations Lung Infection	0.00% 0/3 • Up to 3 years	25.0% 1/4 • Number of events 1 • Up to 3 years	8.3% 1/12 • Number of events 1 • Up to 3 years
Gastrointestinal disorders Nausea	100.0% 3/3 • Number of events 3 • Up to 3 years	25.0% 1/4 • Number of events 1 • Up to 3 years	0.00% 0/12 • Up to 3 years
Blood and lymphatic system disorders Neutropenia	66.7% 2/3 • Number of events 2 • Up to 3 years	0.00% 0/4 • Up to 3 years	0.00% 0/12 • Up to 3 years
Skin and subcutaneous tissue disorders Rash	33.3% 1/3 • Number of events 1 • Up to 3 years	50.0% 2/4 • Number of events 2 • Up to 3 years	0.00% 0/12 • Up to 3 years
Respiratory, thoracic and mediastinal disorders Respiratory	66.7% 2/3 • Number of events 2 • Up to 3 years	25.0% 1/4 • Number of events 1 • Up to 3 years	8.3% 1/12 • Number of events 1 • Up to 3 years
Infections and infestations Sepsis	33.3% 1/3 • Number of events 1 • Up to 3 years	25.0% 1/4 • Number of events 1 • Up to 3 years	8.3% 1/12 • Number of events 1 • Up to 3 years
Metabolism and nutrition disorders Tumor Lysis Syndrome	33.3% 1/3 • Number of events 1 • Up to 3 years	0.00% 0/4 • Up to 3 years	8.3% 1/12 • Number of events 1 • Up to 3 years
Gastrointestinal disorders Vomiting	100.0% 3/3 • Number of events 3 • Up to 3 years	25.0% 1/4 • Number of events 1 • Up to 3 years	8.3% 1/12 • Number of events 1 • Up to 3 years
General disorders Pain	66.7% 2/3 • Number of events 3 • Up to 3 years	50.0% 2/4 • Number of events 2 • Up to 3 years	0.00% 0/12 • Up to 3 years

Additional Information

Farhad Ravandi-Kashani MD/Professor

The University of Texas MD Anderson Cancer Center

Phone: 713-745-0394

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place