Trial Outcomes & Findings for Phase I/II Study of 5-Azacytidine With Ara-C in Patients With Relapsed/Refractory Acute Myelogenous Leukemia (AML) or High Risk Myelodysplastic Syndrome (MDS) (NCT NCT00569010)

Last Updated: 2012-08-01

Results Overview

Clinical response is determined by achievement of a complete remission (CR) as judged by morphological criteria (\< 1% blasts in bone marrow with neutrophil recovery) according to International Working Group (IWG) criteria.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

36 participants

Primary outcome timeframe

6 weeks

Results posted on

2012-08-01

Participant Flow

Recruitment Period 12/28/2005 to 8/25/2008. All participants were registered at The University of Texas M.D. Anderson Cancer Center.

Of the 36 enrolled, only 34 evaluable participants were included in this study and started study drug.

Participant milestones

Participant milestones
Measure	Low-Dose Ara-C + AZA-Level 0 Low-Dose Ara-C: 100 mg/m\^2 Daily continuous intravenous infusion (CIV) for 7 days; Azacitidine (AZA): 37.5 mg/m\^2 intravenous (IV) Over 20-30 minutes Daily for 7 Days	Low-Dose Ara-C + AZA-Level 1 Low-Dose Ara-C: 100 mg/m\^2 Daily continuous intravenous infusion (CIV) for 7 days AZA: Level 1 = 75.0 mg/m\^2 IV Over 20-30 minutes Daily for 7 days	High-Dose Ara-C + AZA-Level 0 Ara-C: 1 g/m\^2 Daily CIV for 4 days (age\<65years) or 3 days (age\>=65years); AZA: 37.5 mg/m\^2 IV Over 20-30 minutes Daily for 7 Days	High-Dose Ara-C + AZA-Level 1 High-dose Ara-C: 1 g/m\^2 Daily CIV for 4 days (age\<65years) or 3 days (age\>=65 years); AZA: Level 1 = 75.0 mg/m\^2 IV Over 20-30 minutes Daily for 7 days
Overall Study STARTED	6	6	11	11
Overall Study COMPLETED	6	6	11	11
Overall Study NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Phase I/II Study of 5-Azacytidine With Ara-C in Patients With Relapsed/Refractory Acute Myelogenous Leukemia (AML) or High Risk Myelodysplastic Syndrome (MDS)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Low-Dose Ara-C + AZA-Level 0 n=6 Participants Low-Dose Ara-C: 100 mg/m\^2 Daily continuous intravenous infusion (CIV) for 7 days; Azacitidine (AZA): 37.5 mg/m\^2 intravenous (IV) Over 20-30 minutes Daily for 7 Days	Low-Dose Ara-C + AZA-Level 1 n=6 Participants Low-Dose Ara-C: 100 mg/m\^2 Daily continuous intravenous infusion (CIV) for 7 days AZA: Level 1 = 75.0 mg/m\^2 IV Over 20-30 minutes Daily for 7 days	High-Dose Ara-C + AZA-Level 0 n=11 Participants Ara-C: 1 g/m\^2 Daily CIV for 4 days (age\<65years) or 3 days (age\>=65years); AZA: 37.5 mg/m\^2 IV Over 20-30 minutes Daily for 7 Days	High-Dose Ara-C + AZA-Level 1 n=11 Participants High-dose Ara-C: 1 g/m\^2 Daily CIV for 4 days (age\<65years) or 3 days (age\>=65 years); AZA: Level 1 = 75.0 mg/m\^2 IV Over 20-30 minutes Daily for 7 days	Total n=34 Participants Total of all reporting groups
Age Continuous	44 years n=5 Participants	61 years n=7 Participants	74 years n=5 Participants	62 years n=4 Participants	61 years n=21 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	4 Participants n=7 Participants	3 Participants n=5 Participants	5 Participants n=4 Participants	15 Participants n=21 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	2 Participants n=7 Participants	8 Participants n=5 Participants	6 Participants n=4 Participants	19 Participants n=21 Participants
Region of Enrollment United States	6 participants n=5 Participants	6 participants n=7 Participants	11 participants n=5 Participants	11 participants n=4 Participants	34 participants n=21 Participants

PRIMARY outcome

Timeframe: 6 weeks

Population: Analysis was per protocol.

Outcome measures

Outcome measures
Measure	Low-Dose Ara-C + AZA-Level 0 n=6 Participants Low-Dose Ara-C: 100 mg/m\^2 Daily continuous intravenous infusion (CIV) for 7 days; Azacitidine (AZA): 37.5 mg/m\^2 intravenous (IV) Over 20-30 minutes Daily for 7 Days	Low-Dose Ara-C + AZA-Level 1 n=6 Participants Low-Dose Ara-C: 100 mg/m\^2 Daily continuous intravenous infusion (CIV) for 7 days AZA: Level 1 = 75.0 mg/m\^2 IV Over 20-30 minutes Daily for 7 days	High-Dose Ara-C + AZA-Level 0 n=11 Participants Ara-C: 1 g/m\^2 Daily CIV for 4 days (age\<65years) or 3 days (age\>=65years); AZA: 37.5 mg/m\^2 IV Over 20-30 minutes Daily for 7 Days	High-Dose Ara-C + AZA-Level 1 n=11 Participants High-dose Ara-C: 1 g/m\^2 Daily CIV for 4 days (age\<65years) or 3 days (age\>=65 years); AZA: Level 1 = 75.0 mg/m\^2 IV Over 20-30 minutes Daily for 7 days
Number of Participants With Complete Remission	0 participants	0 participants	0 participants	2 participants

Adverse Events

Low-Dose Ara-C + AZA-Level 0

Serious events: 5 serious events

Other events: 3 other events

Deaths: 0 deaths

Low-Dose Ara-C + AZA-Level 1

Serious events: 5 serious events

Other events: 0 other events

Deaths: 0 deaths

High-Dose Ara-C + AZA-Level 0

Serious events: 8 serious events

Other events: 0 other events

Deaths: 0 deaths

High-Dose Ara-C + AZA-Level 1

Serious events: 3 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Low-Dose Ara-C + AZA-Level 0 n=6 participants at risk Low-Dose Ara-C: 100 mg/m\^2 Daily continuous intravenous infusion (CIV) for 7 days; Azacitidine (AZA): 37.5 mg/m\^2 intravenous (IV) Over 20-30 minutes Daily for 7 Days	Low-Dose Ara-C + AZA-Level 1 n=6 participants at risk Low-Dose Ara-C: 100 mg/m\^2 Daily continuous intravenous infusion (CIV) for 7 days AZA: Level 1 = 75.0 mg/m\^2 IV Over 20-30 minutes Daily for 7 days	High-Dose Ara-C + AZA-Level 0 n=11 participants at risk Ara-C: 1 g/m\^2 Daily CIV for 4 days (age\<65years) or 3 days (age\>=65years); AZA: 37.5 mg/m\^2 IV Over 20-30 minutes Daily for 7 Days	High-Dose Ara-C + AZA-Level 1 n=11 participants at risk High-dose Ara-C: 1 g/m\^2 Daily CIV for 4 days (age\<65years) or 3 days (age\>=65 years); AZA: Level 1 = 75.0 mg/m\^2 IV Over 20-30 minutes Daily for 7 days
Respiratory, thoracic and mediastinal disorders Pneumonia	16.7% 1/6 • Number of events 1 • 2 years 4 months	33.3% 2/6 • Number of events 2 • 2 years 4 months	0.00% 0/11 • 2 years 4 months	0.00% 0/11 • 2 years 4 months
Gastrointestinal disorders colotis	16.7% 1/6 • Number of events 1 • 2 years 4 months	0.00% 0/6 • 2 years 4 months	0.00% 0/11 • 2 years 4 months	0.00% 0/11 • 2 years 4 months
General disorders Disease Progression	16.7% 1/6 • Number of events 1 • 2 years 4 months	0.00% 0/6 • 2 years 4 months	0.00% 0/11 • 2 years 4 months	0.00% 0/11 • 2 years 4 months
Cardiac disorders Heart Disease	0.00% 0/6 • 2 years 4 months	0.00% 0/6 • 2 years 4 months	9.1% 1/11 • Number of events 1 • 2 years 4 months	0.00% 0/11 • 2 years 4 months
Gastrointestinal disorders Mucositis	0.00% 0/6 • 2 years 4 months	16.7% 1/6 • Number of events 1 • 2 years 4 months	0.00% 0/11 • 2 years 4 months	0.00% 0/11 • 2 years 4 months
Cardiac disorders Atrial Fibrillation	0.00% 0/6 • 2 years 4 months	0.00% 0/6 • 2 years 4 months	9.1% 1/11 • Number of events 1 • 2 years 4 months	0.00% 0/11 • 2 years 4 months
Vascular disorders Intracranial Hemorrhage	0.00% 0/6 • 2 years 4 months	0.00% 0/6 • 2 years 4 months	9.1% 1/11 • Number of events 1 • 2 years 4 months	0.00% 0/11 • 2 years 4 months
Infections and infestations Infection	0.00% 0/6 • 2 years 4 months	16.7% 1/6 • Number of events 1 • 2 years 4 months	9.1% 1/11 • Number of events 1 • 2 years 4 months	18.2% 2/11 • Number of events 2 • 2 years 4 months
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/6 • 2 years 4 months	0.00% 0/6 • 2 years 4 months	9.1% 1/11 • Number of events 1 • 2 years 4 months	0.00% 0/11 • 2 years 4 months
Cardiac disorders Cardiac Infarction	0.00% 0/6 • 2 years 4 months	0.00% 0/6 • 2 years 4 months	9.1% 1/11 • Number of events 1 • 2 years 4 months	0.00% 0/11 • 2 years 4 months
Renal and urinary disorders Renal Failure	0.00% 0/6 • 2 years 4 months	0.00% 0/6 • 2 years 4 months	9.1% 1/11 • Number of events 1 • 2 years 4 months	0.00% 0/11 • 2 years 4 months
Skin and subcutaneous tissue disorders Rash	0.00% 0/6 • 2 years 4 months	16.7% 1/6 • Number of events 1 • 2 years 4 months	18.2% 2/11 • Number of events 2 • 2 years 4 months	0.00% 0/11 • 2 years 4 months
Cardiac disorders Tachycardia	0.00% 0/6 • 2 years 4 months	0.00% 0/6 • 2 years 4 months	9.1% 1/11 • Number of events 1 • 2 years 4 months	0.00% 0/11 • 2 years 4 months
Gastrointestinal disorders Diarrhea	0.00% 0/6 • 2 years 4 months	0.00% 0/6 • 2 years 4 months	0.00% 0/11 • 2 years 4 months	9.1% 1/11 • Number of events 1 • 2 years 4 months
Eye disorders Occular/Visual other 20/400	16.7% 1/6 • Number of events 1 • 2 years 4 months	0.00% 0/6 • 2 years 4 months	0.00% 0/11 • 2 years 4 months	0.00% 0/11 • 2 years 4 months
Respiratory, thoracic and mediastinal disorders Pleural Effusion	16.7% 1/6 • Number of events 1 • 2 years 4 months	0.00% 0/6 • 2 years 4 months	0.00% 0/11 • 2 years 4 months	0.00% 0/11 • 2 years 4 months

Other adverse events

Other adverse events
Measure	Low-Dose Ara-C + AZA-Level 0 n=6 participants at risk Low-Dose Ara-C: 100 mg/m\^2 Daily continuous intravenous infusion (CIV) for 7 days; Azacitidine (AZA): 37.5 mg/m\^2 intravenous (IV) Over 20-30 minutes Daily for 7 Days	Low-Dose Ara-C + AZA-Level 1 n=6 participants at risk Low-Dose Ara-C: 100 mg/m\^2 Daily continuous intravenous infusion (CIV) for 7 days AZA: Level 1 = 75.0 mg/m\^2 IV Over 20-30 minutes Daily for 7 days	High-Dose Ara-C + AZA-Level 0 n=11 participants at risk Ara-C: 1 g/m\^2 Daily CIV for 4 days (age\<65years) or 3 days (age\>=65years); AZA: 37.5 mg/m\^2 IV Over 20-30 minutes Daily for 7 Days	High-Dose Ara-C + AZA-Level 1 n=11 participants at risk High-dose Ara-C: 1 g/m\^2 Daily CIV for 4 days (age\<65years) or 3 days (age\>=65 years); AZA: Level 1 = 75.0 mg/m\^2 IV Over 20-30 minutes Daily for 7 days
Gastrointestinal disorders Diarrhea	50.0% 3/6 • Number of events 3 • 2 years 4 months	0.00% 0/6 • 2 years 4 months	0.00% 0/11 • 2 years 4 months	45.5% 5/11 • Number of events 5 • 2 years 4 months
Gastrointestinal disorders Mucositis	0.00% 0/6 • 2 years 4 months	0.00% 0/6 • 2 years 4 months	0.00% 0/11 • 2 years 4 months	9.1% 1/11 • Number of events 1 • 2 years 4 months
Gastrointestinal disorders Vomiting	0.00% 0/6 • 2 years 4 months	0.00% 0/6 • 2 years 4 months	0.00% 0/11 • 2 years 4 months	9.1% 1/11 • Number of events 1 • 2 years 4 months

Additional Information

Jean-Pierre Issa, M.D./Professor

The University of MD Anderson Cancer Center

Phone: 713-745-2260

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place