Trial Outcomes & Findings for Study to Investigate the Efficacy, Safety and Tolerability of AZD1152 Alone and in Combination With Low Dose Cytosine Arabinoside (LDAC)in Acute Myeloid Leukaemia (AML) Patients (NCT NCT00952588)
NCT ID: NCT00952588
Last Updated: 2020-02-24
Results Overview
Percentage of patients achieving either a complete response (CR) or a confirmed complete remission with incomplete recovery of neutrophils or platelets (confirmed CRi). Per Cheson Criteria: Confirmed complete remission (CRi) is defined as a disappearance of blasts in the peripheral blood; a decrease in bone marrow blasts to \<5% total bone marrow nucleated cells demonstrated in bone marrow aspirate; absence of Auer rods; no persistent extramedullary leukaemia. Complete response (CR) is defined as all requirements to meet CRi and in addition: recovery of neutrophils to ≥1.0 x 109/L and platelets to ≥100 x 109/L; transfusion-independence.
COMPLETED
PHASE2/PHASE3
74 participants
IWG Cheson criteria every 28 days from randomization for study duration (24 months, between 2009 - 2011)
2020-02-24
Participant Flow
First patient was randomized on 22/07/2009 and last patient last visit has occurred on 27/06/2011.
Participant milestones
| Measure |
AZD1152 1200mg
AZD1152 1200 mg, iv, 7 day infusion monotherapy
|
LDAC 20mg
LDAC 20 mg, sc, bd, 10 days (400mg per cycle)
|
|---|---|---|
|
Overall Study
STARTED
|
48
|
26
|
|
Overall Study
COMPLETED
|
12
|
2
|
|
Overall Study
NOT COMPLETED
|
36
|
24
|
Reasons for withdrawal
| Measure |
AZD1152 1200mg
AZD1152 1200 mg, iv, 7 day infusion monotherapy
|
LDAC 20mg
LDAC 20 mg, sc, bd, 10 days (400mg per cycle)
|
|---|---|---|
|
Overall Study
Death
|
28
|
13
|
|
Overall Study
Withdrawal by Subject
|
2
|
5
|
|
Overall Study
Adverse Event
|
2
|
3
|
|
Overall Study
Lost to Follow-up
|
2
|
0
|
|
Overall Study
Physician Decision
|
0
|
1
|
|
Overall Study
Lack of Efficacy
|
2
|
2
|
Baseline Characteristics
Study to Investigate the Efficacy, Safety and Tolerability of AZD1152 Alone and in Combination With Low Dose Cytosine Arabinoside (LDAC)in Acute Myeloid Leukaemia (AML) Patients
Baseline characteristics by cohort
| Measure |
AZD1152 1200mg
n=48 Participants
AZD1152 1200 mg, iv, 7 day infusion monotherapy
|
LDAC 20mg
n=26 Participants
LDAC 20 mg, sc, bd, 10 days (400mg per cycle)
|
Total
n=74 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
75.3 years
STANDARD_DEVIATION 5.79 • n=5 Participants
|
71.5 years
STANDARD_DEVIATION 5.75 • n=7 Participants
|
74.0 years
STANDARD_DEVIATION 6.03 • n=5 Participants
|
|
Sex: Female, Male
Female
|
23 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
31 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
25 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
43 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: IWG Cheson criteria every 28 days from randomization for study duration (24 months, between 2009 - 2011)Population: modified Intent to Treat (ITT)
Percentage of patients achieving either a complete response (CR) or a confirmed complete remission with incomplete recovery of neutrophils or platelets (confirmed CRi). Per Cheson Criteria: Confirmed complete remission (CRi) is defined as a disappearance of blasts in the peripheral blood; a decrease in bone marrow blasts to \<5% total bone marrow nucleated cells demonstrated in bone marrow aspirate; absence of Auer rods; no persistent extramedullary leukaemia. Complete response (CR) is defined as all requirements to meet CRi and in addition: recovery of neutrophils to ≥1.0 x 109/L and platelets to ≥100 x 109/L; transfusion-independence.
Outcome measures
| Measure |
AZD1152 1200mg
n=48 Participants
AZD1152 1200 mg, iv, 7 day infusion monotherapy
|
LDAC 20mg
n=26 Participants
LDAC 20 mg, sc, bd, 10 days (400mg per cycle)
|
|---|---|---|
|
Percentage of Patients With Overall Complete Response for Stage I
|
35.4 percentage of participants
|
11.5 percentage of participants
|
SECONDARY outcome
Timeframe: DoR was measured every 28 days from randomization for study duration (24 months, between 2009 - 2011)Population: modified Intent to Treat (mITT)
DoR was defined for the median of days which showed a confirmed CRi or CR, as the time from first documented evidence of CRi or CR until the first documented sign of disease progression or death. Duration of Response was measured from the Response Start date until evidence of patient relapse or death. Stage I : 45 patients randomized in a 2:1 ratio to AZD1152 or LDAC. Transition phase: enrollment of up to 30 additional patients randomized as per stage I.
Outcome measures
| Measure |
AZD1152 1200mg
n=17 Participants
AZD1152 1200 mg, iv, 7 day infusion monotherapy
|
LDAC 20mg
n=3 Participants
LDAC 20 mg, sc, bd, 10 days (400mg per cycle)
|
|---|---|---|
|
Duration of Response (DoR): Stage I and Transition Phase
|
82 days
Interval 43.0 to 189.0
|
NA days
This was not calculable because there were only 3 responses (events) in this group and the method of estimating the median was using Kaplan-Meier methods.
|
SECONDARY outcome
Timeframe: DFS was measured every 28 days from randomization for study duration (24 months, between 2009 - 2011)Population: modified Intent to Treat (mITT)
Disease-free Survival is defined as the time from randomisation to relapse or death from any cause.
Outcome measures
| Measure |
AZD1152 1200mg
n=17 Participants
AZD1152 1200 mg, iv, 7 day infusion monotherapy
|
LDAC 20mg
n=3 Participants
LDAC 20 mg, sc, bd, 10 days (400mg per cycle)
|
|---|---|---|
|
Disease Free Survival (DFS)
|
5.6 months
Interval 3.3 to 7.9
|
NA months
This was not calculable because there were only 3 responses (events) in this group and the method of estimating the median was using Kaplan-Meier methods.
|
SECONDARY outcome
Timeframe: Response was measured every 28 days from randomization for study duration (24 months, between 2009 - 2011)Population: modified Intent to Treat (mITT)
TTCR is measured as time from randomization to either a complete response (CR) or a confirmed complete remission with incomplete recovery of neutrophils or platelets (confirmed CRi)
Outcome measures
| Measure |
AZD1152 1200mg
n=17 Participants
AZD1152 1200 mg, iv, 7 day infusion monotherapy
|
LDAC 20mg
n=3 Participants
LDAC 20 mg, sc, bd, 10 days (400mg per cycle)
|
|---|---|---|
|
Time To Complete Response (TTCR)
|
59 days
Interval 27.0 to 180.0
|
64 days
Interval 63.0 to 96.0
|
SECONDARY outcome
Timeframe: Assessed from randomisation until the date of death from any cause, assessed up to 24 monthsPopulation: modified Intent to Treat (mITT)
Overall Survival is defined as the median time from randomisation to death from any cause. Patients who were not known to have died at the time of the analysis were censored at the date they were last known to be alive.
Outcome measures
| Measure |
AZD1152 1200mg
n=48 Participants
AZD1152 1200 mg, iv, 7 day infusion monotherapy
|
LDAC 20mg
n=26 Participants
LDAC 20 mg, sc, bd, 10 days (400mg per cycle)
|
|---|---|---|
|
Overall Survival (OS)
|
8.2 months
Full Range 43 • Interval 0.1 to 15.9
|
4.5 months
Full Range 32 • Interval 0.2 to 20.4
|
SECONDARY outcome
Timeframe: TOI was measured every 28 days from randomization for study duration (24 months, between 2009 - 2011)Population: modified Intent to Treat (mITT)
TOI is derived from the sum of the Functional Well Being (FWB), Physical Well Being (PWB) and additional subscales of the FACT-Leu. The TOI subscale consists of 31 items with TOI scores ranging from 0 to 124. The TOI is described as a summary measure of HRQoL. Higher scores indicate better HRQoL. Negative changes from baseline indicate a worsening of HRQoL while positive changes indicate an improvement in HRQoL. A response of "Worsened" was a change from baseline in score of less than or equal to -9.
Outcome measures
| Measure |
AZD1152 1200mg
n=48 Participants
AZD1152 1200 mg, iv, 7 day infusion monotherapy
|
LDAC 20mg
n=26 Participants
LDAC 20 mg, sc, bd, 10 days (400mg per cycle)
|
|---|---|---|
|
Percent of Patients With Worsened Trial Outcome Index (TOI)
|
31.3 percentage of participants
|
11.5 percentage of participants
|
SECONDARY outcome
Timeframe: FACT-Leu was measured every 28 days from randomization for study duration (24 months, between 2009 - 2011)Population: modified Intent to Treat (mITT)
The total FACT-Leu score consists of 44 items with total scores ranging from 0 to 176. Higher scores indicate better HRQoL. Negative changes from baseline indicate a worsening of HRQoL while positive changes indicate an improvement in HRQoL. A response of "Worsened" was a change from baseline in score of less than or equal to -11.
Outcome measures
| Measure |
AZD1152 1200mg
n=48 Participants
AZD1152 1200 mg, iv, 7 day infusion monotherapy
|
LDAC 20mg
n=26 Participants
LDAC 20 mg, sc, bd, 10 days (400mg per cycle)
|
|---|---|---|
|
Percent of Patients With Worsened Functional Assessment of Cancer Therapy - Leukaemia (FACT-Leu) Score.
|
29.2 percentage of participants
|
11.5 percentage of participants
|
Adverse Events
AZD1152 1200mg
LDAC 20mg
Serious adverse events
| Measure |
AZD1152 1200mg
n=48 participants at risk
AZD1152 1200 mg, iv, 7 day infusion monotherapy
|
LDAC 20mg
n=26 participants at risk
LDAC 20 mg, sc, bd, 10 days (400mg per cycle)
|
|---|---|---|
|
Blood and lymphatic system disorders
Febrile Neutropenia
|
10.4%
5/48
|
0.00%
0/26
|
|
Blood and lymphatic system disorders
Neutropenia
|
4.2%
2/48
|
0.00%
0/26
|
|
Blood and lymphatic system disorders
Anaemia
|
2.1%
1/48
|
3.8%
1/26
|
|
Blood and lymphatic system disorders
Febrile Bone Marrow Aplasia
|
0.00%
0/48
|
3.8%
1/26
|
|
Blood and lymphatic system disorders
Pancytopenia
|
2.1%
1/48
|
0.00%
0/26
|
|
Cardiac disorders
Angina Pectoris
|
2.1%
1/48
|
0.00%
0/26
|
|
Cardiac disorders
Atrial Fibrillation
|
2.1%
1/48
|
0.00%
0/26
|
|
Cardiac disorders
Myocardial Ischaemia
|
2.1%
1/48
|
0.00%
0/26
|
|
Gastrointestinal disorders
Stomatitis
|
6.2%
3/48
|
0.00%
0/26
|
|
General disorders
Pyrexia
|
8.3%
4/48
|
3.8%
1/26
|
|
General disorders
Device Occlusion
|
2.1%
1/48
|
0.00%
0/26
|
|
General disorders
Hyperthermia
|
2.1%
1/48
|
0.00%
0/26
|
|
Infections and infestations
Pneumonia
|
12.5%
6/48
|
7.7%
2/26
|
|
Infections and infestations
Arthritis Infective
|
2.1%
1/48
|
0.00%
0/26
|
|
Infections and infestations
Cellulitis
|
2.1%
1/48
|
0.00%
0/26
|
|
Infections and infestations
Clostridium Difficile Sepsis
|
0.00%
0/48
|
3.8%
1/26
|
|
Infections and infestations
Enterococcal Bacteraemia
|
2.1%
1/48
|
0.00%
0/26
|
|
Infections and infestations
Escherichia Infection
|
2.1%
1/48
|
0.00%
0/26
|
|
Infections and infestations
Lobar Pneumonia
|
2.1%
1/48
|
0.00%
0/26
|
|
Infections and infestations
Lung Infection
|
0.00%
0/48
|
3.8%
1/26
|
|
Infections and infestations
Neutropenic Sepsis
|
0.00%
0/48
|
3.8%
1/26
|
|
Infections and infestations
Oral Candidiasis
|
2.1%
1/48
|
0.00%
0/26
|
|
Infections and infestations
Pulmonary Mycosis
|
2.1%
1/48
|
0.00%
0/26
|
|
Infections and infestations
Sepsis
|
2.1%
1/48
|
3.8%
1/26
|
|
Injury, poisoning and procedural complications
Subdural Haematoma
|
2.1%
1/48
|
0.00%
0/26
|
|
Investigations
White Blood Cell Count Increased
|
0.00%
0/48
|
3.8%
1/26
|
|
Musculoskeletal and connective tissue disorders
Myopathy
|
2.1%
1/48
|
0.00%
0/26
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Blast Cell Proliferation
|
2.1%
1/48
|
0.00%
0/26
|
|
Nervous system disorders
Convulsion
|
2.1%
1/48
|
0.00%
0/26
|
|
Nervous system disorders
Presyncope
|
2.1%
1/48
|
0.00%
0/26
|
|
Renal and urinary disorders
Renal Failure
|
2.1%
1/48
|
0.00%
0/26
|
|
Renal and urinary disorders
Renal Failure Acute
|
2.1%
1/48
|
0.00%
0/26
|
|
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Distress Syndrome
|
2.1%
1/48
|
0.00%
0/26
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/48
|
3.8%
1/26
|
|
Respiratory, thoracic and mediastinal disorders
Lung Infiltration
|
2.1%
1/48
|
0.00%
0/26
|
|
Respiratory, thoracic and mediastinal disorders
Pleural Effusion
|
0.00%
0/48
|
3.8%
1/26
|
|
Vascular disorders
Hypertension
|
2.1%
1/48
|
0.00%
0/26
|
|
Vascular disorders
Thrombophlebitis
|
2.1%
1/48
|
0.00%
0/26
|
Other adverse events
| Measure |
AZD1152 1200mg
n=48 participants at risk
AZD1152 1200 mg, iv, 7 day infusion monotherapy
|
LDAC 20mg
n=26 participants at risk
LDAC 20 mg, sc, bd, 10 days (400mg per cycle)
|
|---|---|---|
|
Blood and lymphatic system disorders
Febrile Neutropenia
|
66.7%
32/48
|
19.2%
5/26
|
|
Blood and lymphatic system disorders
Anaemia
|
25.0%
12/48
|
11.5%
3/26
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
18.8%
9/48
|
23.1%
6/26
|
|
Blood and lymphatic system disorders
Leukopenia
|
12.5%
6/48
|
0.00%
0/26
|
|
Blood and lymphatic system disorders
Neutropenia
|
10.4%
5/48
|
7.7%
2/26
|
|
Blood and lymphatic system disorders
Lymphopenia
|
8.3%
4/48
|
0.00%
0/26
|
|
Blood and lymphatic system disorders
Coagulopathy
|
6.2%
3/48
|
3.8%
1/26
|
|
Cardiac disorders
Tachycardia
|
6.2%
3/48
|
11.5%
3/26
|
|
Ear and labyrinth disorders
Vertigo
|
6.2%
3/48
|
0.00%
0/26
|
|
Eye disorders
Conjunctival Haemorrhage
|
6.2%
3/48
|
0.00%
0/26
|
|
Gastrointestinal disorders
Stomatitis
|
68.8%
33/48
|
15.4%
4/26
|
|
Gastrointestinal disorders
Diarrhoea
|
50.0%
24/48
|
11.5%
3/26
|
|
Gastrointestinal disorders
Constipation
|
47.9%
23/48
|
30.8%
8/26
|
|
Gastrointestinal disorders
Nausea
|
43.8%
21/48
|
38.5%
10/26
|
|
Gastrointestinal disorders
Vomiting
|
35.4%
17/48
|
19.2%
5/26
|
|
Gastrointestinal disorders
Haemorrhoids
|
14.6%
7/48
|
3.8%
1/26
|
|
Gastrointestinal disorders
Oral Pain
|
10.4%
5/48
|
0.00%
0/26
|
|
Gastrointestinal disorders
Abdominal Pain
|
6.2%
3/48
|
15.4%
4/26
|
|
Gastrointestinal disorders
Dry Mouth
|
8.3%
4/48
|
0.00%
0/26
|
|
Gastrointestinal disorders
Dyspepsia
|
8.3%
4/48
|
0.00%
0/26
|
|
Gastrointestinal disorders
Dysphagia
|
8.3%
4/48
|
3.8%
1/26
|
|
Gastrointestinal disorders
Tongue Ulceration
|
8.3%
4/48
|
3.8%
1/26
|
|
Gastrointestinal disorders
Abdominal Pain Upper
|
6.2%
3/48
|
0.00%
0/26
|
|
Gastrointestinal disorders
Gingival Bleeding
|
6.2%
3/48
|
11.5%
3/26
|
|
Gastrointestinal disorders
Toothache
|
6.2%
3/48
|
0.00%
0/26
|
|
General disorders
Pyrexia
|
27.1%
13/48
|
30.8%
8/26
|
|
General disorders
Fatigue
|
18.8%
9/48
|
23.1%
6/26
|
|
General disorders
Asthenia
|
14.6%
7/48
|
30.8%
8/26
|
|
General disorders
Oedema Peripheral
|
16.7%
8/48
|
26.9%
7/26
|
|
General disorders
Hyperthermia
|
10.4%
5/48
|
0.00%
0/26
|
|
General disorders
Oedema
|
8.3%
4/48
|
3.8%
1/26
|
|
General disorders
Pain
|
8.3%
4/48
|
3.8%
1/26
|
|
General disorders
Catheter Site Pain
|
6.2%
3/48
|
7.7%
2/26
|
|
General disorders
Catheter Site Related Reaction
|
6.2%
3/48
|
0.00%
0/26
|
|
General disorders
Chills
|
6.2%
3/48
|
11.5%
3/26
|
|
General disorders
Catheter Site Haematoma
|
0.00%
0/48
|
7.7%
2/26
|
|
General disorders
Injection Site Haematoma
|
0.00%
0/48
|
7.7%
2/26
|
|
Infections and infestations
Pneumonia
|
12.5%
6/48
|
3.8%
1/26
|
|
Infections and infestations
Sepsis
|
12.5%
6/48
|
0.00%
0/26
|
|
Infections and infestations
Oral Candidiasis
|
10.4%
5/48
|
0.00%
0/26
|
|
Infections and infestations
Bacteraemia
|
6.2%
3/48
|
0.00%
0/26
|
|
Infections and infestations
Cellulitis
|
6.2%
3/48
|
0.00%
0/26
|
|
Injury, poisoning and procedural complications
Contusion
|
6.2%
3/48
|
3.8%
1/26
|
|
Investigations
Alanine Aminotransferase Increased
|
8.3%
4/48
|
0.00%
0/26
|
|
Investigations
Weight Decreased
|
6.2%
3/48
|
15.4%
4/26
|
|
Investigations
Blood Creatinine Increased
|
6.2%
3/48
|
3.8%
1/26
|
|
Investigations
Breath Sounds Abnormal
|
6.2%
3/48
|
0.00%
0/26
|
|
Investigations
Blood Pressure Decreased
|
0.00%
0/48
|
7.7%
2/26
|
|
Investigations
Weight Increased
|
0.00%
0/48
|
7.7%
2/26
|
|
Metabolism and nutrition disorders
Decreased Appetite
|
20.8%
10/48
|
19.2%
5/26
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
20.8%
10/48
|
7.7%
2/26
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
10.4%
5/48
|
0.00%
0/26
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
8.3%
4/48
|
3.8%
1/26
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
8.3%
4/48
|
3.8%
1/26
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
0.00%
0/48
|
7.7%
2/26
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
16.7%
8/48
|
7.7%
2/26
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Chest Pain
|
10.4%
5/48
|
0.00%
0/26
|
|
Musculoskeletal and connective tissue disorders
Bone Pain
|
2.1%
1/48
|
11.5%
3/26
|
|
Musculoskeletal and connective tissue disorders
Joint Swelling
|
6.2%
3/48
|
3.8%
1/26
|
|
Musculoskeletal and connective tissue disorders
Pain In Extremity
|
4.2%
2/48
|
11.5%
3/26
|
|
Musculoskeletal and connective tissue disorders
Muscle Spasms
|
2.1%
1/48
|
7.7%
2/26
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Pain
|
4.2%
2/48
|
7.7%
2/26
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/48
|
7.7%
2/26
|
|
Nervous system disorders
Headache
|
16.7%
8/48
|
3.8%
1/26
|
|
Nervous system disorders
Dysgeusia
|
10.4%
5/48
|
0.00%
0/26
|
|
Nervous system disorders
Dizziness
|
8.3%
4/48
|
15.4%
4/26
|
|
Psychiatric disorders
Insomnia
|
22.9%
11/48
|
11.5%
3/26
|
|
Psychiatric disorders
Anxiety
|
8.3%
4/48
|
3.8%
1/26
|
|
Psychiatric disorders
Confusional State
|
8.3%
4/48
|
3.8%
1/26
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
22.9%
11/48
|
23.1%
6/26
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
16.7%
8/48
|
19.2%
5/26
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
14.6%
7/48
|
11.5%
3/26
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal Pain
|
14.6%
7/48
|
0.00%
0/26
|
|
Respiratory, thoracic and mediastinal disorders
Pleural Effusion
|
8.3%
4/48
|
0.00%
0/26
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
6.2%
3/48
|
11.5%
3/26
|
|
Respiratory, thoracic and mediastinal disorders
Rales
|
4.2%
2/48
|
7.7%
2/26
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
22.9%
11/48
|
0.00%
0/26
|
|
Skin and subcutaneous tissue disorders
Rash
|
20.8%
10/48
|
7.7%
2/26
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.00%
0/48
|
15.4%
4/26
|
|
Skin and subcutaneous tissue disorders
Petechiae
|
8.3%
4/48
|
15.4%
4/26
|
|
Skin and subcutaneous tissue disorders
Erythema
|
2.1%
1/48
|
11.5%
3/26
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
6.2%
3/48
|
3.8%
1/26
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
2.1%
1/48
|
7.7%
2/26
|
|
Vascular disorders
Hypotension
|
10.4%
5/48
|
3.8%
1/26
|
|
Vascular disorders
Haematoma
|
4.2%
2/48
|
11.5%
3/26
|
|
Vascular disorders
Pallor
|
0.00%
0/48
|
7.7%
2/26
|
|
Vascular disorders
Phlebitis
|
2.1%
1/48
|
7.7%
2/26
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60