Trial Outcomes & Findings for Selumetinib in Treating Patients With Recurrent or Refractory Acute Myeloid Leukemia (NCT NCT00588809)
NCT ID: NCT00588809
Last Updated: 2015-08-05
Results Overview
Responses were defined using standard criteria developed by an International Working Group. \[Cheson BD, Bennett JM, Kopecky KJ, Buchner T, Willman CL, Estey EH, et al. Revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. J Clin Oncol 2003;21:4642-9.\] In this primary outcome, we report the proportion of subjects without FLT3 ITD mutation that experienced a complete response (CR), partial response (PR), minor response (MR), or unconfirmed minor response (uMR).
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
47 participants
Primary outcome timeframe
Up to 52 weeks
Results posted on
2015-08-05
Participant Flow
A Simon, optimal two-stage design was employed for subjects without FLT3 ITD mutations. The study also included a second cohort of subjects with FLT3 ITD mutations.
Participant milestones
| Measure |
Selumetinib
Patients receive selumetinib PO BID on days 1 -28. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.
selumetinib: Given PO
|
|---|---|
|
Overall Study
COMPLETED
|
47
|
|
Overall Study
STARTED
|
47
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Selumetinib in Treating Patients With Recurrent or Refractory Acute Myeloid Leukemia
Baseline characteristics by cohort
| Measure |
Selumetinib
n=47 Participants
Patients receive selumetinib PO BID on days 1 -28. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.
selumetinib: Given PO
|
|---|---|
|
Age, Continuous
|
69 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
20 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
27 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 52 weeksPopulation: Analysis only includes subjects without FLT3 ITD mutation.
Responses were defined using standard criteria developed by an International Working Group. \[Cheson BD, Bennett JM, Kopecky KJ, Buchner T, Willman CL, Estey EH, et al. Revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. J Clin Oncol 2003;21:4642-9.\] In this primary outcome, we report the proportion of subjects without FLT3 ITD mutation that experienced a complete response (CR), partial response (PR), minor response (MR), or unconfirmed minor response (uMR).
Outcome measures
| Measure |
Selumetinib
n=36 Participants
Patients receive selumetinib PO BID on days 1 -28. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.
selumetinib: Given PO
|
|---|---|
|
Response Rate for Subjects Without FLT3 ITD Mutation
|
16.67 percentage of participants
|
SECONDARY outcome
Timeframe: baseline (0 weeks)Population: The analysis includes the 20 patients with samples available for analysis.
Proportion of subjects with baseline p-ERK activation
Outcome measures
| Measure |
Selumetinib
n=20 Participants
Patients receive selumetinib PO BID on days 1 -28. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.
selumetinib: Given PO
|
|---|---|
|
Proportion of Subjects With Baseline p-ERK Activation
|
85 percentage of participants
|
SECONDARY outcome
Timeframe: baseline (0 weeks)Population: The analysis includes the 41 patients with samples available for analysis.
Proportion of Subjects With NRAS Mutation
Outcome measures
| Measure |
Selumetinib
n=41 Participants
Patients receive selumetinib PO BID on days 1 -28. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.
selumetinib: Given PO
|
|---|---|
|
Proportion of Subjects With NRAS Mutation
|
7 percentage of participants
|
SECONDARY outcome
Timeframe: baseline (0 weeks)Population: The analysis includes the 41 patients with samples available for analysis.
Proportion of subjects with KRAS mutation
Outcome measures
| Measure |
Selumetinib
n=41 Participants
Patients receive selumetinib PO BID on days 1 -28. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.
selumetinib: Given PO
|
|---|---|
|
Proportion of Subjects With KRAS Mutation
|
2 percentage of participants
|
SECONDARY outcome
Timeframe: baseline (0 weeks)Population: FLT3 ITD mutation status was not available for one patient.
Proportion of subjects with FLT3 ITD mutation
Outcome measures
| Measure |
Selumetinib
n=46 Participants
Patients receive selumetinib PO BID on days 1 -28. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.
selumetinib: Given PO
|
|---|---|
|
Proportion of Subjects With FLT3 ITD Mutation
|
22 percentage of participants
|
SECONDARY outcome
Timeframe: baseline (0 weeks)Population: The analysis includes the 41 patients with samples available for analysis.
Proportion of subjects with KIT mutation
Outcome measures
| Measure |
Selumetinib
n=41 Participants
Patients receive selumetinib PO BID on days 1 -28. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.
selumetinib: Given PO
|
|---|---|
|
Proportion of Subjects With KIT Mutation
|
0 percentage of participants
|
Adverse Events
Selumetinib
Serious events: 38 serious events
Other events: 47 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Selumetinib
n=47 participants at risk
Patients receive selumetinib PO BID on days 1 -28. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.
selumetinib: Given PO
|
|---|---|
|
Blood and lymphatic system disorders
Anemia
|
4.3%
2/47 • 1 year
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
17.0%
8/47 • 1 year
|
|
Cardiac disorders
Ventricular tachycardia
|
2.1%
1/47 • 1 year
|
|
Gastrointestinal disorders
Diarrhea
|
4.3%
2/47 • 1 year
|
|
Gastrointestinal disorders
Dry mouth
|
2.1%
1/47 • 1 year
|
|
Gastrointestinal disorders
Mucositis oral
|
4.3%
2/47 • 1 year
|
|
Gastrointestinal disorders
Nausea
|
4.3%
2/47 • 1 year
|
|
Gastrointestinal disorders
Vomiting
|
6.4%
3/47 • 1 year
|
|
General disorders
Death NOS
|
21.3%
10/47 • 1 year
|
|
General disorders
Fatigue
|
6.4%
3/47 • 1 year
|
|
General disorders
Fever
|
4.3%
2/47 • 1 year
|
|
Infections and infestations
Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L): Blood
|
8.5%
4/47 • 1 year
|
|
Infections and infestations
Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L): Lung (pneumonia)
|
6.4%
3/47 • 1 year
|
|
Infections and infestations
Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L): Rectum
|
2.1%
1/47 • 1 year
|
|
Infections and infestations
Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L): Salivary gland
|
2.1%
1/47 • 1 year
|
|
Infections and infestations
Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L): Skin (cellulitis)
|
2.1%
1/47 • 1 year
|
|
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils: Blood
|
4.3%
2/47 • 1 year
|
|
Infections and infestations
Infections and infestations - Other
|
23.4%
11/47 • 1 year
|
|
Infections and infestations
Lung infection
|
6.4%
3/47 • 1 year
|
|
Infections and infestations
peritonsillar abscess
|
2.1%
1/47 • 1 year
|
|
Infections and infestations
Pharyngitis
|
2.1%
1/47 • 1 year
|
|
Infections and infestations
Sepsis
|
2.1%
1/47 • 1 year
|
|
Infections and infestations
Upper respiratory infection
|
2.1%
1/47 • 1 year
|
|
Infections and infestations
Urinary tract infection
|
2.1%
1/47 • 1 year
|
|
Investigations
Alanine aminotransferase increased
|
2.1%
1/47 • 1 year
|
|
Investigations
Creatinine increased
|
2.1%
1/47 • 1 year
|
|
Investigations
Neutrophil count decreased
|
2.1%
1/47 • 1 year
|
|
Investigations
Platelet count decreased
|
6.4%
3/47 • 1 year
|
|
Investigations
White blood cell decreased
|
2.1%
1/47 • 1 year
|
|
Metabolism and nutrition disorders
Acidosis
|
2.1%
1/47 • 1 year
|
|
Metabolism and nutrition disorders
Anorexia
|
2.1%
1/47 • 1 year
|
|
Metabolism and nutrition disorders
Dehydration
|
10.6%
5/47 • 1 year
|
|
Metabolism and nutrition disorders
Hyperuricemia
|
2.1%
1/47 • 1 year
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
2.1%
1/47 • 1 year
|
|
Metabolism and nutrition disorders
Hypokalemia
|
2.1%
1/47 • 1 year
|
|
Metabolism and nutrition disorders
Hyponatremia
|
2.1%
1/47 • 1 year
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness lower limb
|
2.1%
1/47 • 1 year
|
|
Nervous system disorders
Dizziness
|
4.3%
2/47 • 1 year
|
|
Nervous system disorders
Dysphasia
|
2.1%
1/47 • 1 year
|
|
Nervous system disorders
Intracranial hemorrhage
|
8.5%
4/47 • 1 year
|
|
Psychiatric disorders
Psychosis
|
2.1%
1/47 • 1 year
|
|
Renal and urinary disorders
Urine discoloration
|
2.1%
1/47 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Bronchopulmonary hemorrhage
|
2.1%
1/47 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
4.3%
2/47 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
2.1%
1/47 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
2.1%
1/47 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
6.4%
3/47 • 1 year
|
|
Vascular disorders
Hypotension
|
6.4%
3/47 • 1 year
|
Other adverse events
| Measure |
Selumetinib
n=47 participants at risk
Patients receive selumetinib PO BID on days 1 -28. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.
selumetinib: Given PO
|
|---|---|
|
Blood and lymphatic system disorders
Anemia
|
51.1%
24/47 • 1 year
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
6.4%
3/47 • 1 year
|
|
Cardiac disorders
Atrial fibrillation
|
6.4%
3/47 • 1 year
|
|
Cardiac disorders
Paroxysmal atrial tachycardia
|
8.5%
4/47 • 1 year
|
|
Cardiac disorders
Sinus tachycardia
|
27.7%
13/47 • 1 year
|
|
Gastrointestinal disorders
Abdominal distension
|
14.9%
7/47 • 1 year
|
|
Gastrointestinal disorders
Abdominal pain
|
27.7%
13/47 • 1 year
|
|
Gastrointestinal disorders
Constipation
|
8.5%
4/47 • 1 year
|
|
Gastrointestinal disorders
Diarrhea
|
61.7%
29/47 • 1 year
|
|
Gastrointestinal disorders
Dry mouth
|
12.8%
6/47 • 1 year
|
|
Gastrointestinal disorders
Dyspepsia
|
6.4%
3/47 • 1 year
|
|
Gastrointestinal disorders
Hemorrhoids
|
8.5%
4/47 • 1 year
|
|
Gastrointestinal disorders
Mucositis oral
|
19.1%
9/47 • 1 year
|
|
Gastrointestinal disorders
Nausea
|
51.1%
24/47 • 1 year
|
|
Gastrointestinal disorders
Oral hemorrhage
|
10.6%
5/47 • 1 year
|
|
Gastrointestinal disorders
Vomiting
|
31.9%
15/47 • 1 year
|
|
General disorders
Chills
|
34.0%
16/47 • 1 year
|
|
General disorders
Edema limbs
|
44.7%
21/47 • 1 year
|
|
General disorders
Fatigue
|
68.1%
32/47 • 1 year
|
|
General disorders
Fever
|
44.7%
21/47 • 1 year
|
|
General disorders
Non-cardiac chest pain
|
14.9%
7/47 • 1 year
|
|
General disorders
Pain
|
12.8%
6/47 • 1 year
|
|
Immune system disorders
Allergic reaction
|
10.6%
5/47 • 1 year
|
|
Infections and infestations
Infections and infestations - Other
|
19.1%
9/47 • 1 year
|
|
Infections and infestations
Urinary tract infection
|
6.4%
3/47 • 1 year
|
|
Injury, poisoning and procedural complications
Bruising
|
6.4%
3/47 • 1 year
|
|
Investigations
Alanine aminotransferase increased
|
34.0%
16/47 • 1 year
|
|
Investigations
Alkaline phosphatase increased
|
14.9%
7/47 • 1 year
|
|
Investigations
Aspartate aminotransferase increased
|
40.4%
19/47 • 1 year
|
|
Investigations
Blood bilirubin increased
|
10.6%
5/47 • 1 year
|
|
Investigations
Creatinine increased
|
14.9%
7/47 • 1 year
|
|
Investigations
Lymphocyte count decreased
|
17.0%
8/47 • 1 year
|
|
Investigations
Neutrophil count decreased
|
42.6%
20/47 • 1 year
|
|
Investigations
Platelet count decreased
|
51.1%
24/47 • 1 year
|
|
Investigations
Weight loss
|
6.4%
3/47 • 1 year
|
|
Investigations
White blood cell decreased
|
27.7%
13/47 • 1 year
|
|
Metabolism and nutrition disorders
Acidosis
|
10.6%
5/47 • 1 year
|
|
Metabolism and nutrition disorders
Anorexia
|
40.4%
19/47 • 1 year
|
|
Metabolism and nutrition disorders
Dehydration
|
8.5%
4/47 • 1 year
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
36.2%
17/47 • 1 year
|
|
Metabolism and nutrition disorders
Hyperuricemia
|
6.4%
3/47 • 1 year
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
42.6%
20/47 • 1 year
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
27.7%
13/47 • 1 year
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
6.4%
3/47 • 1 year
|
|
Metabolism and nutrition disorders
Hypokalemia
|
25.5%
12/47 • 1 year
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
19.1%
9/47 • 1 year
|
|
Metabolism and nutrition disorders
Hyponatremia
|
31.9%
15/47 • 1 year
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
10.6%
5/47 • 1 year
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
6.4%
3/47 • 1 year
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
19.1%
9/47 • 1 year
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
8.5%
4/47 • 1 year
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness lower limb
|
8.5%
4/47 • 1 year
|
|
Nervous system disorders
Dizziness
|
21.3%
10/47 • 1 year
|
|
Nervous system disorders
Headache
|
25.5%
12/47 • 1 year
|
|
Psychiatric disorders
Confusion
|
8.5%
4/47 • 1 year
|
|
Psychiatric disorders
Depression
|
8.5%
4/47 • 1 year
|
|
Renal and urinary disorders
Proteinuria
|
8.5%
4/47 • 1 year
|
|
Renal and urinary disorders
Urinary retention
|
6.4%
3/47 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
38.3%
18/47 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
40.4%
19/47 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
19.1%
9/47 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
10.6%
5/47 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
|
8.5%
4/47 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
10.6%
5/47 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
6.4%
3/47 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders - Other, specify
|
6.4%
3/47 • 1 year
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
6.4%
3/47 • 1 year
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
8.5%
4/47 • 1 year
|
|
Skin and subcutaneous tissue disorders
Purpura
|
8.5%
4/47 • 1 year
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
21.3%
10/47 • 1 year
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other
|
6.4%
3/47 • 1 year
|
|
Vascular disorders
Hypertension
|
19.1%
9/47 • 1 year
|
|
Vascular disorders
Hypotension
|
14.9%
7/47 • 1 year
|
|
Vascular disorders
Vascular disorders - Other
|
10.6%
5/47 • 1 year
|
Additional Information
Olatoyosi Odenike, MD
The University of Chicago Medicine
Phone: (773) 702-6149
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60