Trial Outcomes & Findings for Sorafenib Plus 5-Azacitidine Initial Therapy of Patients With Acute Myeloid Leukemia (AML) and High Risk Myelodysplastic Syndrome (MS) With FLT3-ITD Mutation (NCT NCT02196857)
NCT ID: NCT02196857
Last Updated: 2020-01-14
Results Overview
Criteria for response per the International Working Group for myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Complete Response (CR) was defined as \</= 5% blasts in the bone marrow (BM) with peripheral blood (PB) demonstrating greater thatn 1x10\^9/L platelets with no detectable extramedullary disease. CR with incomplete recovery of PB counts (CRi) is the above criteria but neutrophil or platelet counts less than the stated values. Partial Response (PR) required all of the hematologic values for a CR but with a reduction of at least 50% in the percentage of blasts to 5% to 25% in the bone marrow aspirate.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
16 participants
Primary outcome timeframe
After 3, 28 day cycles
Results posted on
2020-01-14
Participant Flow
Recruitment Period: February 2015 - February 2018
Participant milestones
| Measure |
Azacytidine + Sorafenib
Azacitidine 75 mg/m2 administered subcutaneously (SQ) or intravenously (IV) daily for 7 days per 28 day cycle. Sorafenib administered orally at a dose of 400 mg twice daily every day continuously.
Azacytidine: 75 mg/m2 administered subcutaneously (SQ) or intravenously (IV) on Days 1 - 7 for a 28 day cycle.
Sorafenib: 400 mg by mouth twice daily about 12 hours apart, every day for a 28 day cycle.
|
|---|---|
|
Overall Study
STARTED
|
16
|
|
Overall Study
COMPLETED
|
16
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Sorafenib Plus 5-Azacitidine Initial Therapy of Patients With Acute Myeloid Leukemia (AML) and High Risk Myelodysplastic Syndrome (MS) With FLT3-ITD Mutation
Baseline characteristics by cohort
| Measure |
Azacytidine + Sorafenib
n=16 Participants
Azacitidine 75 mg/m2 administered subcutaneously (SQ) or intravenously (IV) daily for 7 days per 28 day cycle. Sorafenib administered orally at a dose of 400 mg twice daily every day continuously.
Azacytidine: 75 mg/m2 administered subcutaneously (SQ) or intravenously (IV) on Days 1 - 7 for a 28 day cycle.
Sorafenib: 400 mg by mouth twice daily about 12 hours apart, every day for a 28 day cycle.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
16 Participants
n=5 Participants
|
|
Age, Continuous
|
75 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
13 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
16 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: After 3, 28 day cyclesCriteria for response per the International Working Group for myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Complete Response (CR) was defined as \</= 5% blasts in the bone marrow (BM) with peripheral blood (PB) demonstrating greater thatn 1x10\^9/L platelets with no detectable extramedullary disease. CR with incomplete recovery of PB counts (CRi) is the above criteria but neutrophil or platelet counts less than the stated values. Partial Response (PR) required all of the hematologic values for a CR but with a reduction of at least 50% in the percentage of blasts to 5% to 25% in the bone marrow aspirate.
Outcome measures
| Measure |
Azacytidine + Sorafenib
n=16 Participants
Azacitidine 75 mg/m2 administered subcutaneously (SQ) or intravenously (IV) daily for 7 days per 28 day cycle. Sorafenib administered orally at a dose of 400 mg twice daily every day continuously.
Azacytidine: 75 mg/m2 administered subcutaneously (SQ) or intravenously (IV) on Days 1 - 7 for a 28 day cycle.
Sorafenib: 400 mg by mouth twice daily about 12 hours apart, every day for a 28 day cycle.
|
|---|---|
|
Participants With a Response CR + PR + CRi
Complete Response (CR)
|
4 Participants
|
|
Participants With a Response CR + PR + CRi
Partial Response (PR)
|
1 Participants
|
|
Participants With a Response CR + PR + CRi
CR with incomplete platelet recovery (CRi)
|
4 Participants
|
SECONDARY outcome
Timeframe: After 3, 28 day cyclesSeverity of toxicities graded according to the NCI Common Toxicity Criteria for Adverse Effects (CTCAE) v4.0. Standard reporting guidelines followed for adverse events. Safety data summarized by category, severity and frequency.
Outcome measures
| Measure |
Azacytidine + Sorafenib
n=6 Participants
Azacitidine 75 mg/m2 administered subcutaneously (SQ) or intravenously (IV) daily for 7 days per 28 day cycle. Sorafenib administered orally at a dose of 400 mg twice daily every day continuously.
Azacytidine: 75 mg/m2 administered subcutaneously (SQ) or intravenously (IV) on Days 1 - 7 for a 28 day cycle.
Sorafenib: 400 mg by mouth twice daily about 12 hours apart, every day for a 28 day cycle.
|
|---|---|
|
Toxicity Profile of Azacytidine and Sorafenib
Diarrhea
|
4 Participants
|
|
Toxicity Profile of Azacytidine and Sorafenib
Dyspnea
|
2 Participants
|
|
Toxicity Profile of Azacytidine and Sorafenib
Fatigue
|
5 Participants
|
|
Toxicity Profile of Azacytidine and Sorafenib
Febrile Neutropenia
|
4 Participants
|
|
Toxicity Profile of Azacytidine and Sorafenib
Nausea
|
2 Participants
|
|
Toxicity Profile of Azacytidine and Sorafenib
Pain
|
2 Participants
|
|
Toxicity Profile of Azacytidine and Sorafenib
Rash/Desquamation
|
2 Participants
|
Adverse Events
Azacytidine + Sorafenib
Serious events: 14 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Azacytidine + Sorafenib
n=16 participants at risk
Azacitidine 75 mg/m2 administered subcutaneously (SQ) or intravenously (IV) daily for 7 days per 28 day cycle. Sorafenib administered orally at a dose of 400 mg twice daily every day continuously.
Azacytidine: 75 mg/m2 administered subcutaneously (SQ) or intravenously (IV) on Days 1 - 7 for a 28 day cycle.
Sorafenib: 400 mg by mouth twice daily about 12 hours apart, every day for a 28 day cycle.
|
|---|---|
|
Cardiac disorders
Acute Heart Failure
|
6.2%
1/16 • Number of events 1 • Up to three years
|
|
Renal and urinary disorders
Acute Kidney failure
|
6.2%
1/16 • Number of events 1 • Up to three years
|
|
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Failure
|
6.2%
1/16 • Number of events 1 • Up to three years
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
6.2%
1/16 • Number of events 1 • Up to three years
|
|
Blood and lymphatic system disorders
Cardiac Triponin Increase
|
6.2%
1/16 • Number of events 1 • Up to three years
|
|
Infections and infestations
Cellulitis
|
6.2%
1/16 • Number of events 2 • Up to three years
|
|
Gastrointestinal disorders
Colitis
|
12.5%
2/16 • Number of events 4 • Up to three years
|
|
Gastrointestinal disorders
Dehydration
|
6.2%
1/16 • Number of events 1 • Up to three years
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
12.5%
2/16 • Number of events 2 • Up to three years
|
|
General disorders
Facial Pain/Dental
|
6.2%
1/16 • Number of events 1 • Up to three years
|
|
General disorders
Fatigue
|
6.2%
1/16 • Number of events 2 • Up to three years
|
|
Infections and infestations
Febrile Neutropenia
|
31.2%
5/16 • Number of events 8 • Up to three years
|
|
General disorders
Fever
|
6.2%
1/16 • Number of events 1 • Up to three years
|
|
Infections and infestations
Urinary Tract Infection
|
12.5%
2/16 • Number of events 2 • Up to three years
|
|
Vascular disorders
Hypotnesion
|
25.0%
4/16 • Number of events 4 • Up to three years
|
|
Infections and infestations
Infection
|
6.2%
1/16 • Number of events 1 • Up to three years
|
|
Gastrointestinal disorders
Intestine Obstruction
|
6.2%
1/16 • Number of events 1 • Up to three years
|
|
Blood and lymphatic system disorders
Intracranial Hemorrhage
|
6.2%
1/16 • Number of events 1 • Up to three years
|
|
Respiratory, thoracic and mediastinal disorders
Laryngeal Hemorrhage
|
6.2%
1/16 • Number of events 1 • Up to three years
|
|
Respiratory, thoracic and mediastinal disorders
Laryngeal Inflammation
|
12.5%
2/16 • Number of events 2 • Up to three years
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
6.2%
1/16 • Number of events 1 • Up to three years
|
|
Infections and infestations
Lung Infection
|
31.2%
5/16 • Number of events 12 • Up to three years
|
|
Renal and urinary disorders
generalized edema
|
6.2%
1/16 • Number of events 1 • Up to three years
|
|
Nervous system disorders
Seizure
|
6.2%
1/16 • Number of events 1 • Up to three years
|
|
Infections and infestations
Sepsis
|
6.2%
1/16 • Number of events 1 • Up to three years
|
|
Infections and infestations
Skin Infection
|
6.2%
1/16 • Number of events 1 • Up to three years
|
|
Nervous system disorders
Stroke
|
6.2%
1/16 • Number of events 1 • Up to three years
|
|
Nervous system disorders
Syncope
|
6.2%
1/16 • Number of events 1 • Up to three years
|
|
Nervous system disorders
Tremor
|
6.2%
1/16 • Number of events 1 • Up to three years
|
Other adverse events
| Measure |
Azacytidine + Sorafenib
n=16 participants at risk
Azacitidine 75 mg/m2 administered subcutaneously (SQ) or intravenously (IV) daily for 7 days per 28 day cycle. Sorafenib administered orally at a dose of 400 mg twice daily every day continuously.
Azacytidine: 75 mg/m2 administered subcutaneously (SQ) or intravenously (IV) on Days 1 - 7 for a 28 day cycle.
Sorafenib: 400 mg by mouth twice daily about 12 hours apart, every day for a 28 day cycle.
|
|---|---|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
6.2%
1/16 • Number of events 1 • Up to three years
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
6.2%
1/16 • Number of events 1 • Up to three years
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
6.2%
1/16 • Number of events 1 • Up to three years
|
|
Gastrointestinal disorders
Diarrhea
|
25.0%
4/16 • Number of events 4 • Up to three years
|
|
Nervous system disorders
Dizziness
|
6.2%
1/16 • Number of events 1 • Up to three years
|
|
Respiratory, thoracic and mediastinal disorders
Dyspena
|
12.5%
2/16 • Number of events 2 • Up to three years
|
|
General disorders
Edema
|
6.2%
1/16 • Number of events 1 • Up to three years
|
|
General disorders
Fatigue
|
25.0%
4/16 • Number of events 5 • Up to three years
|
|
General disorders
Hemorrhage
|
6.2%
1/16 • Number of events 1 • Up to three years
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
6.2%
1/16 • Number of events 1 • Up to three years
|
|
Infections and infestations
Infection
|
6.2%
1/16 • Number of events 1 • Up to three years
|
|
Gastrointestinal disorders
Nausea
|
12.5%
2/16 • Number of events 2 • Up to three years
|
|
General disorders
Pain
|
12.5%
2/16 • Number of events 2 • Up to three years
|
|
Skin and subcutaneous tissue disorders
Rash
|
6.2%
1/16 • Number of events 2 • Up to three years
|
|
Gastrointestinal disorders
Vomiting
|
6.2%
1/16 • Number of events 1 • Up to three years
|
|
Eye disorders
Watery eye
|
6.2%
1/16 • Number of events 1 • Up to three years
|
|
Infections and infestations
Febrile Neutropenia
|
25.0%
4/16 • Number of events 4 • Up to three years
|
Additional Information
Ravandi-Kashani,Farhad 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