Trial Outcomes & Findings for Azacitidine With or Without Entinostat in Treating Patients With Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, or Acute Myeloid Leukemia (NCT NCT00313586)

Last Updated: 2017-02-02

Results Overview

Clinical response is defined as a complete response (CR), partial response (PR) or trilineage response (TR) graded according to the following criteria: 1. World Health Organization classification of the acute leukemias and myelodysplastic syndrome (by Bennett) 2. Myelodysplastic syndromes standardized response criteria: further definition (by Cheson et al.) 3. Report of an international working group to standardize response criteria for myelodysplastic syndromes (by Cheson et al.)

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

197 participants

Primary outcome timeframe

Assessed every 3 months if patient is < 2 years from study entry, every 6 months if patient is 2 - 5 years from study entry.

Results posted on

2017-02-02

Participant Flow

Participants were recruited from ECOG member institutions between August 18, 2006 and April 29, 2011. One hundred and fifty non-treatment-induced patients and forty-seven treatment-induced patients were enrolled.

Participant milestones

Participant milestones
Measure	Arm A (Azacitidine; Non-treatment-induced Cohort) Non-treatment-induced patients receive azacitidine (50 mg/m2) subcutaneously once daily on days 1-10 in a 28-day cycle.	Arm B (Azacitidine + Entinostat; Non-treatment-induced Cohort) Non-treatment-induced patients receive azacitidine as in arm A and oral entinostat (4 mg/m2) on days 3 and 10 of each 28-day cycle.	Arm A (Azacitidine; Treatment-induced Cohort) Treatment-induced patients receive azacitidine (50 mg/m2) subcutaneously once daily on days 1-10 in a 28-day cycle.	Arm B (Azacitidine + Entinostat; Treatment-induced Cohort) Treatment-induced patients receive azacitidine as in arm A and oral entinostat (4 mg/m2) on days 3 and 10 of each 28-day cycle.
Overall Study STARTED	75	75	24	23
Overall Study Treated	74	75	24	23
Overall Study COMPLETED	5	5	0	0
Overall Study NOT COMPLETED	70	70	24	23

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm A (Azacitidine; Non-treatment-induced Cohort) Non-treatment-induced patients receive azacitidine (50 mg/m2) subcutaneously once daily on days 1-10 in a 28-day cycle.	Arm B (Azacitidine + Entinostat; Non-treatment-induced Cohort) Non-treatment-induced patients receive azacitidine as in arm A and oral entinostat (4 mg/m2) on days 3 and 10 of each 28-day cycle.	Arm A (Azacitidine; Treatment-induced Cohort) Treatment-induced patients receive azacitidine (50 mg/m2) subcutaneously once daily on days 1-10 in a 28-day cycle.	Arm B (Azacitidine + Entinostat; Treatment-induced Cohort) Treatment-induced patients receive azacitidine as in arm A and oral entinostat (4 mg/m2) on days 3 and 10 of each 28-day cycle.
Overall Study Disease progression	14	19	10	3
Overall Study Adverse Event	12	18	3	10
Overall Study Death	11	8	1	7
Overall Study Withdrawal by Subject	13	6	6	2
Overall Study Alternative therapy	3	6	2	0
Overall Study Other complicating disease	2	2	0	0
Overall Study Did not achieve HI-major/better response	10	7	2	1
Overall Study Physician Decision	2	1	0	0
Overall Study Absolute neutrophil count not recovered	2	1	0	0
Overall Study Lost insurance	0	1	0	0
Overall Study Moved	0	1	0	0
Overall Study Death before starting treatment	1	0	0	0

Baseline Characteristics

Azacitidine With or Without Entinostat in Treating Patients With Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, or Acute Myeloid Leukemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A (Azacitidine; Non-treatment-induced Cohort) n=74 Participants Non-treatment-induced patients receive azacitidine (50 mg/m2) subcutaneously once daily on days 1-10 in a 28-day cycle.	Arm B (Azacitidine + Entinostat; Non-treatment-induced Cohort) n=75 Participants Non-treatment-induced patients receive azacitidine as in arm A and oral entinostat (4 mg/m2) on days 3 and 10 of each 28-day cycle.	Arm A (Azacitidine; Treatment-induced Cohort) n=24 Participants Treatment-induced patients receive azacitidine (50 mg/m2) subcutaneously once daily on days 1-10 in a 28-day cycle.	Arm B (Azacitidine + Entinostat; Treatment-induced Cohort) n=23 Participants Treatment-induced patients receive azacitidine as in arm A and oral entinostat (4 mg/m2) on days 3 and 10 of each 28-day cycle.	Total n=196 Participants Total of all reporting groups
Age, Continuous	72 years n=5 Participants	72 years n=7 Participants	68 years n=5 Participants	71 years n=4 Participants	71 years n=21 Participants
Gender Female	24 Participants n=5 Participants	23 Participants n=7 Participants	15 Participants n=5 Participants	11 Participants n=4 Participants	73 Participants n=21 Participants
Gender Male	50 Participants n=5 Participants	52 Participants n=7 Participants	9 Participants n=5 Participants	12 Participants n=4 Participants	123 Participants n=21 Participants
Region of Enrollment United States	74 participants n=5 Participants	75 participants n=7 Participants	24 participants n=5 Participants	23 participants n=4 Participants	196 participants n=21 Participants

PRIMARY outcome

Timeframe: Assessed every 3 months if patient is < 2 years from study entry, every 6 months if patient is 2 - 5 years from study entry.

Population: All treated patients are included in the analysis.

Outcome measures

Outcome measures
Measure	Arm A (Azacitidine; Non-treatment-induced Cohort) n=74 Participants Non-treatment-induced patients receive azacitidine (50 mg/m2) subcutaneously once daily on days 1-10 in a 28-day cycle.	Arm B (Azacitidine + Entinostat; Non-treatment-induced Cohort) n=75 Participants Non-treatment-induced patients receive azacitidine as in arm A and oral entinostat (4 mg/m2) on days 3 and 10 of each 28-day cycle.	Arm A (Azacitidine; Treatment-induced Cohort) n=24 Participants Treatment-induced patients receive azacitidine (50 mg/m2) subcutaneously once daily on days 1-10 in a 28-day cycle.	Arm B (Azacitidine + Entinostat; Treatment-induced Cohort) n=23 Participants Treatment-induced patients receive azacitidine as in arm A and oral entinostat (4 mg/m2) on days 3 and 10 of each 28-day cycle.
Proportion of Patients With Clinical Response	0.32 Proportion of patients Interval 0.22 to 0.44	0.27 Proportion of patients Interval 0.17 to 0.39	0.46 Proportion of patients Interval 0.26 to 0.67	0.17 Proportion of patients Interval 0.05 to 0.39

Adverse Events

Arm A (Azacitidine)

Serious events: 92 serious events

Other events: 96 other events

Deaths: 0 deaths

Arm B (Azacitidine + Entinostat)

Serious events: 93 serious events

Other events: 97 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Study Statistician

ECOG Statistical Office

Phone: 617-632-3012

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Arm A (Azacitidine) n=99 participants at risk Patients receive azacitidine (50 mg/m2) subcutaneously once daily on days 1-10 in a 28-day cycle.	Arm B (Azacitidine + Entinostat) n=98 participants at risk Patients receive azacitidine as in arm A and oral entinostat (4 mg/m2) on days 3 and 10 of each 28-day cycle.
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	5.1% 5/99 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment	4.1% 4/98 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
Blood and lymphatic system disorders Hemoglobin	80.8% 80/99 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment	75.5% 74/98 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
Investigations Leukocytes	67.7% 67/99 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment	58.2% 57/98 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
Investigations Lymphopenia	11.1% 11/99 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment	8.2% 8/98 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
Investigations Neutrophils	56.6% 56/99 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment	50.0% 49/98 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
Investigations Platelets	63.6% 63/99 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment	58.2% 57/98 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
Vascular disorders Hypotension	2.0% 2/99 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment	8.2% 8/98 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
General disorders Fatigue	71.7% 71/99 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment	72.4% 71/98 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
General disorders Fever w/o neutropenia	10.1% 10/99 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment	7.1% 7/98 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
Psychiatric disorders Insomnia	8.1% 8/99 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment	10.2% 10/98 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
General disorders Rigors/chills	4.0% 4/99 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment	5.1% 5/98 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
Skin and subcutaneous tissue disorders Sweating	6.1% 6/99 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment	6.1% 6/98 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
Investigations Weight loss	8.1% 8/99 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment	15.3% 15/98 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
Injury, poisoning and procedural complications Bruising	6.1% 6/99 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment	6.1% 6/98 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
Skin and subcutaneous tissue disorders Alopecia	6.1% 6/99 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment	9.2% 9/98 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
General disorders Injection site reaction	41.4% 41/99 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment	42.9% 42/98 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
Skin and subcutaneous tissue disorders Pruritus/itching	5.1% 5/99 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment	7.1% 7/98 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
Skin and subcutaneous tissue disorders Rash/desquamation	11.1% 11/99 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment	13.3% 13/98 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
Metabolism and nutrition disorders Anorexia	27.3% 27/99 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment	50.0% 49/98 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
Gastrointestinal disorders Constipation	37.4% 37/99 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment	39.8% 39/98 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
Metabolism and nutrition disorders Dehydration	3.0% 3/99 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment	9.2% 9/98 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
Gastrointestinal disorders Diarrhea w/o prior colostomy	28.3% 28/99 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment	40.8% 40/98 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
Gastrointestinal disorders Dyspepsia	7.1% 7/99 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment	10.2% 10/98 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
Gastrointestinal disorders Muco/stomatitis by exam, oral cavity	4.0% 4/99 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment	5.1% 5/98 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
Gastrointestinal disorders Nausea	49.5% 49/99 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment	56.1% 55/98 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
Nervous system disorders Taste disturbance	9.1% 9/99 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment	18.4% 18/98 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
Gastrointestinal disorders Vomiting	22.2% 22/99 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment	30.6% 30/98 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
Respiratory, thoracic and mediastinal disorders Nose, hemorrhage	3.0% 3/99 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment	12.2% 12/98 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
Skin and subcutaneous tissue disorders Petechiae	4.0% 4/99 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment	9.2% 9/98 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
General disorders Edema limb	7.1% 7/99 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment	23.5% 23/98 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
Metabolism and nutrition disorders Hypoalbuminemia	22.2% 22/99 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment	41.8% 41/98 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
Investigations Alkaline phosphatase	11.1% 11/99 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment	17.3% 17/98 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
Investigations ALT, SGPT	15.2% 15/99 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment	12.2% 12/98 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
Investigations AST, SGOT	14.1% 14/99 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment	11.2% 11/98 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
Investigations Bilirubin	11.1% 11/99 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment	11.2% 11/98 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
Metabolism and nutrition disorders Hypocalcemia	16.2% 16/99 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment	42.9% 42/98 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
Investigations Creatinine	18.2% 18/99 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment	26.5% 26/98 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
Metabolism and nutrition disorders Hyperglycemia	30.3% 30/99 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment	40.8% 40/98 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
Metabolism and nutrition disorders Hypomagnesemia	3.0% 3/99 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment	5.1% 5/98 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
Metabolism and nutrition disorders Hypophosphatemia	2.0% 2/99 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment	8.2% 8/98 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
Metabolism and nutrition disorders Hypokalemia	7.1% 7/99 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment	14.3% 14/98 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
Metabolism and nutrition disorders Hyponatremia	24.2% 24/99 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment	36.7% 36/98 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
Musculoskeletal and connective tissue disorders Nonneuropathic generalized weakness	1.0% 1/99 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment	7.1% 7/98 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
Nervous system disorders Dizziness	3.0% 3/99 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment	11.2% 11/98 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
Nervous system disorders Neuropathy-sensory	2.0% 2/99 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment	8.2% 8/98 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
Gastrointestinal disorders Abdomen, pain	9.1% 9/99 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment	13.3% 13/98 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
Nervous system disorders Head/headache	9.1% 9/99 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment	16.3% 16/98 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
Musculoskeletal and connective tissue disorders Joint, pain	3.0% 3/99 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment	10.2% 10/98 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
Musculoskeletal and connective tissue disorders Muscle, pain	1.0% 1/99 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment	7.1% 7/98 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
Respiratory, thoracic and mediastinal disorders Cough	6.1% 6/99 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment	9.2% 9/98 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
Respiratory, thoracic and mediastinal disorders Dyspnea	15.2% 15/99 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment	22.4% 22/98 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment