Trial Outcomes & Findings for Sorafenib and 5-Azacitidine in Acute Leukemia + Myelodysplastic Syndrome (NCT NCT01254890)

Last Updated: 2016-05-06

Results Overview

MTD is defined as highest dose level in which 6 patients treated with at most 1 experiencing a dose limiting toxicity (DLT) during 1st cycle. One cycle of therapy is 7 days of azacitidine (AZA) and 28 days of sorafenib. Starting dose of Sorafenib is 200 mg twice a day azacitidine

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

60 participants

Primary outcome timeframe

28 day cycle

Results posted on

2016-05-06

Participant Flow

Recruitment Period: January 11, 2011 to February 4, 2013. All recruitment done at The University of Texas (UT) MD Anderson Cancer Center.

Participant milestones

Participant milestones
Measure	Phase I: Azacitidine + Sorafenib Azacitidine (AZA) 75 mg/m\^2 subcutaneously (SQ) or intravenously (IV) daily for 7 days and Sorafenib starting dose 200 mg orally twice a day for 28 Day cycle.	Phase II: Azacitidine + 400 mg Sorafenib Azacitidine (AZA) 75 mg/m\^2 subcutaneously (SQ) or intravenously (IV) daily for 7 days and Sorafenib 400 mg orally twice a day for 28 Day cycle.
Overall Study STARTED	3	57
Overall Study COMPLETED	2	47
Overall Study NOT COMPLETED	1	10

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase I: Azacitidine + Sorafenib Azacitidine (AZA) 75 mg/m\^2 subcutaneously (SQ) or intravenously (IV) daily for 7 days and Sorafenib starting dose 200 mg orally twice a day for 28 Day cycle.	Phase II: Azacitidine + 400 mg Sorafenib Azacitidine (AZA) 75 mg/m\^2 subcutaneously (SQ) or intravenously (IV) daily for 7 days and Sorafenib 400 mg orally twice a day for 28 Day cycle.
Overall Study Ineligible	0	3
Overall Study Withdrawal by Subject	1	2
Overall Study Disease Progression	0	5

Baseline Characteristics

Sorafenib and 5-Azacitidine in Acute Leukemia + Myelodysplastic Syndrome

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase I: Azacitidine + Sorafenib n=3 Participants Azacitidine (AZA) 75 mg/m\^2 subcutaneously (SQ) or intravenously (IV) daily for 7 days and Sorafenib starting dose 200 mg orally twice a day for 28 Day cycle.	Phase II: Azacitidine + 400 Sorafenib n=57 Participants Azacitidine (AZA) 75 mg/m\^2 subcutaneously (SQ) or intravenously (IV) daily for 7 days and Sorafenib 400 mg orally twice a day for 28 Day cycle.	Total n=60 Participants Total of all reporting groups
Age, Continuous	73 years n=5 Participants	64 years n=7 Participants	64 years n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	27 Participants n=7 Participants	28 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	30 Participants n=7 Participants	32 Participants n=5 Participants
Region of Enrollment United States	3 participants n=5 Participants	57 participants n=7 Participants	60 participants n=5 Participants

PRIMARY outcome

Timeframe: 28 day cycle

Outcome measures

Outcome measures
Measure	Azacitidine + Sorafenib n=3 Participants Azacitidine (AZA) 75 mg/m\^2 subcutaneously (SQ) or intravenously (IV) daily for 7 days and Sorafenib starting dose 200 mg orally twice a day for 28 Day cycle.
Phase I: Maximum Tolerated Dose (MTD) of Sorafenib Given With Azacitidine	400 mg/twice daily

SECONDARY outcome

Timeframe: 90 days

Population: Nine participants were not evaluable for response.

Response according to International Working Group response criteria for Acute myeloid leukemia (AML) (JCO 2003; 21: 4642-9): CR defined by presence of \<5% blasts in the bone marrow (BM), with \>1 X 10\^9/L neutrophils and \>100 x 10\^9/L platelets in the peripheral blood (PB) with no detectable extramedullary disease. Participants who met the above criteria but had neutrophil or platelet counts less than the stated values were considered to have achieved CRi (CR with incomplete recovery of PB counts) or CR with incomplete platelet recovery (CRp) if CR but platelets \< 100 x 10\^9/L but ≥ 50 x 10\^9/L and platelet transfusion independent. Partial response (PR) required all of the hematologic values for a CR but with a decrease of \>/= 50% in the percentage of blasts to 5% to 25% in the BM aspirate.

Outcome measures

Outcome measures
Measure	Azacitidine + Sorafenib n=48 Participants Azacitidine (AZA) 75 mg/m\^2 subcutaneously (SQ) or intravenously (IV) daily for 7 days and Sorafenib starting dose 200 mg orally twice a day for 28 Day cycle.
Phase II: Number of Participants With Response Partial Response	1 participants
Phase II: Number of Participants With Response Complete Response (CR)	8 participants
Phase II: Number of Participants With Response Complete Remission Without Platelet Recovery (CRi)	10 participants
Phase II: Number of Participants With Response Complete Response (CRp)	6 participants
Phase II: Number of Participants With Response No Response	23 participants

Adverse Events

Phase I: Azacitidine + Sorafenib

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Phase II: Azacitidine + Sorafenib

Serious events: 0 serious events

Other events: 51 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Farhad Ravandi-Kashani, Professor, Leukemia Department

University of Texas (UT) MD Anderson Cancer Center

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Other adverse events
Measure	Phase I: Azacitidine + Sorafenib n=3 participants at risk Azacitidine (AZA) 75 mg/m\^2 subcutaneously (SQ) or intravenously (IV) daily for 7 days and Sorafenib starting dose 200 mg orally twice a day for 28 Day cycle.	Phase II: Azacitidine + Sorafenib n=57 participants at risk Azacitidine (AZA) 75 mg/m\^2 subcutaneously (SQ) or intravenously (IV) daily for 7 days and Sorafenib starting dose 400 mg orally twice a day for 28 Day cycle.
Metabolism and nutrition disorders Alanine Aminotransferase	66.7% 2/3 • Number of events 2 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.	33.3% 19/57 • Number of events 20 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.
Metabolism and nutrition disorders Aspartate Aminotransferase	66.7% 2/3 • Number of events 2 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.	38.6% 22/57 • Number of events 22 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.
Metabolism and nutrition disorders Bilirubin	100.0% 3/3 • Number of events 3 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.	49.1% 28/57 • Number of events 28 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.
Gastrointestinal disorders Diarrhea	33.3% 1/3 • Number of events 1 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.	26.3% 15/57 • Number of events 15 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.
General disorders Fatigue	66.7% 2/3 • Number of events 2 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.	43.9% 25/57 • Number of events 25 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.
Respiratory, thoracic and mediastinal disorders Atelectasis	33.3% 1/3 • Number of events 1 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.	0.00% 0/57 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.
Nervous system disorders Confusion	33.3% 1/3 • Number of events 1 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.	0.00% 0/57 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.
Gastrointestinal disorders Dysphagia	33.3% 1/3 • Number of events 1 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.	0.00% 0/57 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.
Respiratory, thoracic and mediastinal disorders Dyspnea	33.3% 1/3 • Number of events 1 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.	12.3% 7/57 • Number of events 7 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.
Cardiac disorders Hypertension	33.3% 1/3 • Number of events 1 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.	0.00% 0/57 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.
Metabolism and nutrition disorders Hyperuricemia	33.3% 1/3 • Number of events 1 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.	0.00% 0/57 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.
Nervous system disorders Irritability	33.3% 1/3 • Number of events 1 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.	0.00% 0/57 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.
Respiratory, thoracic and mediastinal disorders Pleural Effusion	33.3% 1/3 • Number of events 1 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.	1.8% 1/57 • Number of events 1 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.
Metabolism and nutrition disorders Creatinine	33.3% 1/3 • Number of events 1 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.	21.1% 12/57 • Number of events 12 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.
Respiratory, thoracic and mediastinal disorders Pulmonary - Other	33.3% 1/3 • Number of events 1 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.	0.00% 0/57 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.
Metabolism and nutrition disorders Metabolic/Lab	33.3% 1/3 • Number of events 1 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.	0.00% 0/57 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.
Infections and infestations Febrile Neutropenia	33.3% 1/3 • Number of events 1 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.	22.8% 13/57 • Number of events 14 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.
Skin and subcutaneous tissue disorders Rash	0.00% 0/3 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.	24.6% 14/57 • Number of events 14 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.
Infections and infestations Infection (documented clinically)	0.00% 0/3 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.	45.6% 26/57 • Number of events 62 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.
Gastrointestinal disorders Constipation	0.00% 0/3 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.	8.8% 5/57 • Number of events 5 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.
Gastrointestinal disorders Mucositis (clinical exam)	0.00% 0/3 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.	3.5% 2/57 • Number of events 2 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.
Gastrointestinal disorders Nausea	0.00% 0/3 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.	22.8% 13/57 • Number of events 13 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.
Blood and lymphatic system disorders Neutrophils	0.00% 0/3 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.	22.8% 13/57 • Number of events 13 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.
General disorders Pain	0.00% 0/3 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.	7.0% 4/57 • Number of events 4 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.
Blood and lymphatic system disorders Platelets	0.00% 0/3 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.	10.5% 6/57 • Number of events 6 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.
Skin and subcutaneous tissue disorders Hand-Foot	0.00% 0/3 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.	10.5% 6/57 • Number of events 6 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.
Gastrointestinal disorders Anorexia	0.00% 0/3 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.	10.5% 6/57 • Number of events 6 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.
Infections and infestations Infection with normal ANC	0.00% 0/3 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.	12.3% 7/57 • Number of events 8 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/3 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.	5.3% 3/57 • Number of events 3 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.
General disorders Weight Loss	0.00% 0/3 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.	7.0% 4/57 • Number of events 4 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.
Blood and lymphatic system disorders Hemoglobin	0.00% 0/3 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.	1.8% 1/57 • Number of events 1 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.
Infections and infestations Infection - Other	0.00% 0/3 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.	1.8% 1/57 • Number of events 1 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.
Gastrointestinal disorders Typhlitis	0.00% 0/3 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.	1.8% 1/57 • Number of events 1 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.
Gastrointestinal disorders Vomiting	0.00% 0/3 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.	10.5% 6/57 • Number of events 6 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.
Gastrointestinal disorders Mucositis (functional/symptomatic)	0.00% 0/3 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.	5.3% 3/57 • Number of events 3 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.
Nervous system disorders Neuropathy - Sensory	0.00% 0/3 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.	3.5% 2/57 • Number of events 2 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.
Skin and subcutaneous tissue disorders Dry Skin	0.00% 0/3 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.	1.8% 1/57 • Number of events 1 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.
Eye disorders Blurred Vision	0.00% 0/3 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.	3.5% 2/57 • Number of events 2 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.
Nervous system disorders Dizziness	0.00% 0/3 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.	1.8% 1/57 • Number of events 1 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.
Eye disorders Dry Eye	0.00% 0/3 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.	1.8% 1/57 • Number of events 1 • Adverse events were collected from the time of informed consent to discontinuation of treatment, up to 1 year. Total study period was 3 years and 11 months.