Trial Outcomes & Findings for Phase 1-2 of Azacitidine + Lenalidomide for Previously Untreated Elderly Patients With Acute Myeloid Leukemia (AML) (NCT NCT00890929)
NCT ID: NCT00890929
Last Updated: 2018-06-18
Results Overview
Compete Remission (CR) includes subjects with CR but incomplete recovery of blood counts (CRi). CR was assessed according to the European LeukemiaNet (ELN) guidelines, and is defined as the absence of clonal lymphocytes in the peripheral blood.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
45 participants
Primary outcome timeframe
12 months
Results posted on
2018-06-18
Participant Flow
Participant milestones
| Measure |
Azacitidine Followed by Lenalidomide
Dose escalation then dose expansion
Lenalidomide: 5 mg, 10 mg, 25 mg, and/or 50 mg of lenalidomide administered PO from day 8 to Day 28 of each cycle
Azacitidine: 75 mg/m2 Azacitidine administered intravenously (IV) or subcutaneously (SC) for days 1 to 7 of each cycle
|
|---|---|
|
Overall Study
STARTED
|
45
|
|
Overall Study
Consented & Enrolled
|
45
|
|
Overall Study
Initiated Treatment
|
43
|
|
Overall Study
COMPLETED
|
39
|
|
Overall Study
NOT COMPLETED
|
6
|
Reasons for withdrawal
| Measure |
Azacitidine Followed by Lenalidomide
Dose escalation then dose expansion
Lenalidomide: 5 mg, 10 mg, 25 mg, and/or 50 mg of lenalidomide administered PO from day 8 to Day 28 of each cycle
Azacitidine: 75 mg/m2 Azacitidine administered intravenously (IV) or subcutaneously (SC) for days 1 to 7 of each cycle
|
|---|---|
|
Overall Study
Death before treatment
|
2
|
|
Overall Study
Withdrawal by Subject
|
3
|
|
Overall Study
Physician Decision
|
1
|
Baseline Characteristics
Phase 1-2 of Azacitidine + Lenalidomide for Previously Untreated Elderly Patients With Acute Myeloid Leukemia (AML)
Baseline characteristics by cohort
| Measure |
Azacitidine Followed by Lenalidomide
n=45 Participants
Dose escalation then dose expansion
Lenalidomide: 5 mg, 10 mg, 25 mg, and/or 50 mg of lenalidomide administered PO from day 8 to Day 28 of each cycle
Azacitidine: 75 mg/m2 Azacitidine administered intravenously (IV) or subcutaneously (SC) for days 1 to 7 of each cycle
|
|---|---|
|
Age, Continuous
|
74 years
n=93 Participants
|
|
Sex: Female, Male
Female
|
17 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
28 Participants
n=93 Participants
|
PRIMARY outcome
Timeframe: 12 monthsCompete Remission (CR) includes subjects with CR but incomplete recovery of blood counts (CRi). CR was assessed according to the European LeukemiaNet (ELN) guidelines, and is defined as the absence of clonal lymphocytes in the peripheral blood.
Outcome measures
| Measure |
Azacitidine Followed by Lenalidomide
n=43 Participants
Dose escalation then dose expansion
Lenalidomide: 5 mg, 10 mg, 25 mg, and/or 50 mg of lenalidomide administered PO from day 8 to Day 28 of each cycle
Azacitidine: 75 mg/m2 Azacitidine administered intravenously (IV) or subcutaneously (SC) for days 1 to 7 of each cycle
|
|---|---|
|
Compete Remission (CR) Rate
|
28 percentage of subjects
|
SECONDARY outcome
Timeframe: 28 days"Early death" was assessed as death within 28 days of the start of treatment
Outcome measures
| Measure |
Azacitidine Followed by Lenalidomide
n=43 Participants
Dose escalation then dose expansion
Lenalidomide: 5 mg, 10 mg, 25 mg, and/or 50 mg of lenalidomide administered PO from day 8 to Day 28 of each cycle
Azacitidine: 75 mg/m2 Azacitidine administered intravenously (IV) or subcutaneously (SC) for days 1 to 7 of each cycle
|
|---|---|
|
4-week Survival Rate
|
83 percentage of subjects remaining alive
|
SECONDARY outcome
Timeframe: 15 monthsPopulation: This outcome only includes results from participants in study Phase 1.
The maximum tolerated dose (MTD) of lenalidomide was determined in study phase 1, for use in study Phase 2 (not conducted). The outcome is reported as the dose of lenalidomide that represents the MTD.
Outcome measures
| Measure |
Azacitidine Followed by Lenalidomide
n=43 Participants
Dose escalation then dose expansion
Lenalidomide: 5 mg, 10 mg, 25 mg, and/or 50 mg of lenalidomide administered PO from day 8 to Day 28 of each cycle
Azacitidine: 75 mg/m2 Azacitidine administered intravenously (IV) or subcutaneously (SC) for days 1 to 7 of each cycle
|
|---|---|
|
Maximum Tolerated Dose (MTD) of Lenalidomide
|
50 mg/day lenalidomide (oral)
|
SECONDARY outcome
Timeframe: 26 monthsResponses and remission were assessed according to the ELN guidelines.
Outcome measures
| Measure |
Azacitidine Followed by Lenalidomide
n=43 Participants
Dose escalation then dose expansion
Lenalidomide: 5 mg, 10 mg, 25 mg, and/or 50 mg of lenalidomide administered PO from day 8 to Day 28 of each cycle
Azacitidine: 75 mg/m2 Azacitidine administered intravenously (IV) or subcutaneously (SC) for days 1 to 7 of each cycle
|
|---|---|
|
Remission Duration
|
6 weeks
Interval 6.0 to 104.0
|
SECONDARY outcome
Timeframe: 26 monthsORR includes subjects with CR, CRi, and partial response (PR). Responses were assessed according to the ELN guidelines.
Outcome measures
| Measure |
Azacitidine Followed by Lenalidomide
n=43 Participants
Dose escalation then dose expansion
Lenalidomide: 5 mg, 10 mg, 25 mg, and/or 50 mg of lenalidomide administered PO from day 8 to Day 28 of each cycle
Azacitidine: 75 mg/m2 Azacitidine administered intravenously (IV) or subcutaneously (SC) for days 1 to 7 of each cycle
|
|---|---|
|
Overall Response Rate (ORR)
|
41 percentage of subjects
|
SECONDARY outcome
Timeframe: 88 weeks (median)OS from the start of treatment was assessed at a median follow up of 88 weeks from the end of treatment (range, 1-120), and was censored at 1 April 2012.
Outcome measures
| Measure |
Azacitidine Followed by Lenalidomide
n=43 Participants
Dose escalation then dose expansion
Lenalidomide: 5 mg, 10 mg, 25 mg, and/or 50 mg of lenalidomide administered PO from day 8 to Day 28 of each cycle
Azacitidine: 75 mg/m2 Azacitidine administered intravenously (IV) or subcutaneously (SC) for days 1 to 7 of each cycle
|
|---|---|
|
Overall Survival (OS)
|
20 weeks
Interval 10.0 to 121.0
|
SECONDARY outcome
Timeframe: 18 weeksCR includes subjects with CR but incomplete recovery of blood counts (CRi). Responses were assessed according to the ELN guidelines.
Outcome measures
| Measure |
Azacitidine Followed by Lenalidomide
n=43 Participants
Dose escalation then dose expansion
Lenalidomide: 5 mg, 10 mg, 25 mg, and/or 50 mg of lenalidomide administered PO from day 8 to Day 28 of each cycle
Azacitidine: 75 mg/m2 Azacitidine administered intravenously (IV) or subcutaneously (SC) for days 1 to 7 of each cycle
|
|---|---|
|
Time to CR
|
12 weeks
Interval 6.0 to 18.0
|
SECONDARY outcome
Timeframe: 36 weeksResponses were assessed according to the ELN guidelines.
Outcome measures
| Measure |
Azacitidine Followed by Lenalidomide
n=43 Participants
Dose escalation then dose expansion
Lenalidomide: 5 mg, 10 mg, 25 mg, and/or 50 mg of lenalidomide administered PO from day 8 to Day 28 of each cycle
Azacitidine: 75 mg/m2 Azacitidine administered intravenously (IV) or subcutaneously (SC) for days 1 to 7 of each cycle
|
|---|---|
|
Time to PR
|
6 weeks
Interval 6.0 to 36.0
|
SECONDARY outcome
Timeframe: 88 weeks (median)OS from the start of treatment of responders (per ELN guidelines) was assessed at a median follow up of 88 weeks from the end of treatment (range, 1-120), and was censored at 1 April 2012.
Outcome measures
| Measure |
Azacitidine Followed by Lenalidomide
n=43 Participants
Dose escalation then dose expansion
Lenalidomide: 5 mg, 10 mg, 25 mg, and/or 50 mg of lenalidomide administered PO from day 8 to Day 28 of each cycle
Azacitidine: 75 mg/m2 Azacitidine administered intravenously (IV) or subcutaneously (SC) for days 1 to 7 of each cycle
|
|---|---|
|
OS of Responders
|
69 weeks
Interval 10.0 to 121.0
|
Adverse Events
Azacitidine Followed by Lenalidomide
Serious events: 36 serious events
Other events: 39 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Azacitidine Followed by Lenalidomide
n=43 participants at risk
Dose escalation then dose expansion
Lenalidomide: 5 mg, 10 mg, 25 mg, and/or 50 mg of lenalidomide administered PO from day 8 to Day 28 of each cycle
Azacitidine: 75 mg/m2 Azacitidine administered intravenously (IV) or subcutaneously (SC) for days 1 to 7 of each cycle
|
|---|---|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
55.8%
24/43 • Number of events 37
|
|
Blood and lymphatic system disorders
Blood and lymphatic system disorders - Other, Pancytopenia
|
2.3%
1/43 • Number of events 1
|
|
Blood and lymphatic system disorders
Hemolysis
|
2.3%
1/43 • Number of events 1
|
|
Cardiac disorders
Atrial fibrillation
|
2.3%
1/43 • Number of events 1
|
|
Cardiac disorders
Cardiac disorders - Cardiac arrest
|
2.3%
1/43 • Number of events 1
|
|
Cardiac disorders
Pericarditis
|
2.3%
1/43 • Number of events 1
|
|
Ear and labyrinth disorders
External ear inflammation
|
2.3%
1/43 • Number of events 1
|
|
Gastrointestinal disorders
Colitis
|
2.3%
1/43 • Number of events 1
|
|
Gastrointestinal disorders
Intra-abdominal hemorrhage
|
2.3%
1/43 • Number of events 1
|
|
Gastrointestinal disorders
Upper gastrointestinal hemorrhage
|
2.3%
1/43 • Number of events 1
|
|
General disorders
Death NOS-AML disease
|
4.7%
2/43 • Number of events 2
|
|
General disorders
Death NOS-Cardiopulmonary arrest
|
4.7%
2/43 • Number of events 2
|
|
General disorders
Death NOS-Chills
|
2.3%
1/43 • Number of events 1
|
|
General disorders
Death NOS-Death
|
4.7%
2/43 • Number of events 2
|
|
General disorders
Death NOS- Thrombocytopenia
|
2.3%
1/43 • Number of events 1
|
|
General disorders
Death NOS-Disease progression
|
7.0%
3/43 • Number of events 3
|
|
General disorders
Death NOS-Hypoxia
|
2.3%
1/43 • Number of events 1
|
|
General disorders
Death NOS-pneumonia
|
2.3%
1/43 • Number of events 1
|
|
General disorders
Death NOS-Sepis
|
2.3%
1/43 • Number of events 1
|
|
General disorders
Death NOS-Terminal Ventricular Tachycardia
|
2.3%
1/43 • Number of events 1
|
|
General disorders
Fatigue
|
2.3%
1/43 • Number of events 1
|
|
General disorders
Fever
|
4.7%
2/43 • Number of events 2
|
|
General disorders
Non-cardiac chest pain
|
2.3%
1/43 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal pain
|
2.3%
1/43 • Number of events 1
|
|
Infections and infestations
Sepsis
|
4.7%
2/43 • Number of events 2
|
|
Infections and infestations
Infections and infestations - Other, Neutropenia
|
2.3%
1/43 • Number of events 1
|
|
Investigations
Platelet count decreased
|
4.7%
2/43 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
2.3%
1/43 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
2.3%
1/43 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
2.3%
1/43 • Number of events 2
|
|
Nervous system disorders
Nervous system disorders - Other, high-grade glioblastoma (brain mass)
|
2.3%
1/43 • Number of events 1
|
|
Nervous system disorders
Ischemia cerebrovascular-Acute Stroke
|
2.3%
1/43 • Number of events 1
|
|
Psychiatric disorders
Anxiety
|
2.3%
1/43 • Number of events 1
|
|
Infections and infestations
Urinary tract infection
|
2.3%
1/43 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
9.3%
4/43 • Number of events 4
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders - Other, Pneumonia
|
2.3%
1/43 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders - Other, Respiratory failure
|
4.7%
2/43 • Number of events 2
|
|
Vascular disorders
Hypotension
|
2.3%
1/43 • Number of events 1
|
|
Vascular disorders
Vascular disorders - Other, Dieulafoy's lesion
|
2.3%
1/43 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Bronchopulmonary hemorrhage
|
2.3%
1/43 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
2.3%
1/43 • Number of events 1
|
Other adverse events
| Measure |
Azacitidine Followed by Lenalidomide
n=43 participants at risk
Dose escalation then dose expansion
Lenalidomide: 5 mg, 10 mg, 25 mg, and/or 50 mg of lenalidomide administered PO from day 8 to Day 28 of each cycle
Azacitidine: 75 mg/m2 Azacitidine administered intravenously (IV) or subcutaneously (SC) for days 1 to 7 of each cycle
|
|---|---|
|
Cardiac disorders
Atrial fibrillation
|
11.6%
5/43 • Number of events 5
|
|
Cardiac disorders
Cardiac disorders - other-Systolic Murmur
|
7.0%
3/43 • Number of events 3
|
|
Gastrointestinal disorders
Constipation
|
46.5%
20/43 • Number of events 33
|
|
Gastrointestinal disorders
Diarrhea
|
37.2%
16/43 • Number of events 30
|
|
Gastrointestinal disorders
Dry mouth
|
9.3%
4/43 • Number of events 6
|
|
Gastrointestinal disorders
Dysphagia
|
9.3%
4/43 • Number of events 8
|
|
Gastrointestinal disorders
Hemorrhoids
|
9.3%
4/43 • Number of events 4
|
|
Gastrointestinal disorders
Mucositis oral
|
20.9%
9/43 • Number of events 15
|
|
Gastrointestinal disorders
Nausea
|
53.5%
23/43 • Number of events 50
|
|
Gastrointestinal disorders
Vomiting
|
20.9%
9/43 • Number of events 18
|
|
General disorders
Edema limbs
|
34.9%
15/43 • Number of events 23
|
|
General disorders
Fatigue
|
37.2%
16/43 • Number of events 20
|
|
General disorders
Fever
|
14.0%
6/43 • Number of events 9
|
|
Metabolism and nutrition disorders
Anorexia
|
11.6%
5/43 • Number of events 6
|
|
General disorders
Injection site reaction
|
41.9%
18/43 • Number of events 38
|
|
Infections and infestations
Urinary tract infection
|
11.6%
5/43 • Number of events 6
|
|
Injury, poisoning and procedural complications
Bruising
|
9.3%
4/43 • Number of events 4
|
|
Investigations
Blood bilirubin increased
|
9.3%
4/43 • Number of events 4
|
|
Investigations
Creatinine increased
|
11.6%
5/43 • Number of events 5
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
11.6%
5/43 • Number of events 6
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
7.0%
3/43 • Number of events 4
|
|
Nervous system disorders
Cognitive disturbance
|
7.0%
3/43 • Number of events 4
|
|
Nervous system disorders
Dizziness
|
11.6%
5/43 • Number of events 6
|
|
Nervous system disorders
Dysgeusia
|
7.0%
3/43 • Number of events 3
|
|
Nervous system disorders
Headache
|
7.0%
3/43 • Number of events 3
|
|
Nervous system disorders
Syncope
|
7.0%
3/43 • Number of events 3
|
|
Nervous system disorders
Tremor
|
11.6%
5/43 • Number of events 6
|
|
Renal and urinary disorders
Acute kidney injury
|
14.0%
6/43 • Number of events 7
|
|
Renal and urinary disorders
Urinary retention
|
9.3%
4/43 • Number of events 5
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
32.6%
14/43 • Number of events 18
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
20.9%
9/43 • Number of events 13
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
16.3%
7/43 • Number of events 7
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
7.0%
3/43 • Number of events 3
|
|
Infections and infestations
Infections and infestations -- other, Penumonia
|
14.0%
6/43 • Number of events 6
|
|
Respiratory, thoracic and mediastinal disorders
Sinus disorder
|
7.0%
3/43 • Number of events 3
|
|
Respiratory, thoracic and mediastinal disorders
Voice alteration
|
7.0%
3/43 • Number of events 4
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
9.3%
4/43 • Number of events 6
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
20.9%
9/43 • Number of events 15
|
|
Skin and subcutaneous tissue disorders
Rash acneiform
|
7.0%
3/43 • Number of events 3
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
25.6%
11/43 • Number of events 17
|
|
Investigations
Neutrophil count decreased
|
7.0%
3/43 • Number of events 3
|
Additional Information
Bruno C Medeiros, MD
Stanford University Medical Center
Phone: 650-498-6000
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place