Trial Outcomes & Findings for Cediranib Maleate in Treating Patients With Relapsed, Refractory, or Untreated Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome (NCT NCT00475150)
NCT ID: NCT00475150
Last Updated: 2017-02-15
Results Overview
Complete Response (CR) requires a repeat bone marrow with \< 5% myeloblasts, hemoglobin ≥ 11 g/dl, neutrophils ≥ 1000/mm3, platelets ≥ 100,000/mm3, and no circulating blasts. Partial Response (PR) requires a bone marrow blast reduction of 50% or more, hemoglobin ≥ 11 g/dl, neutrophils ≥ 1000/mm3, platelets ≥ 100,000/mm3, and no circulating blasts. Hematologic Improvement (HI) requires one of the following: 1. RBC transfusion independent participants are required to have \>1.5 g/dL increase in hemoglobin, 2. RBC transfusion-dependent participants are required to be transfusion independent, 3. A 100% increase, and an absolute increase over 500mm\^3 in Absolute Neutrophil Count, 4. Participants with a pretreatment platelet count over 20,000/mm3 require an absolute increase of 30,000/mm\^3 or more, 5. Participants with platelet count below 20,000/mm3 require an increase over 20,000/mm\^3 and by at least 100%.
COMPLETED
PHASE2
39 participants
At the end of cycles 1 and 3 and every 3 cycles thereafter up to 26 cycles
2017-02-15
Participant Flow
Between June 2008 and June 2011, 39 participants were accrued to this study.
A total of 23 AML (7 at 45 mg; 16 at 30 mg) and 16 MDS (all at 30 mg) were enrolled. The AML and MDS groups were analyzed for the primary endpoint separately.
Participant milestones
| Measure |
Acute Myeloid Leukemia (AML)
Patients receive 30 mg oral cediranib maleate QD on days 1-28. Treatment repeats every 28 days for up to 26 courses in the absence of disease progression or unacceptable toxicity.
|
Myelodysplastic Syndrome (MDS)
Patients receive 30 mg oral cediranib maleate QD on days 1-28. Treatment repeats every 28 days for up to 26 courses in the absence of disease progression or unacceptable toxicity.
|
|---|---|---|
|
Overall Study
STARTED
|
23
|
16
|
|
Overall Study
COMPLETED
|
23
|
16
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Cediranib Maleate in Treating Patients With Relapsed, Refractory, or Untreated Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome
Baseline characteristics by cohort
| Measure |
Acute Myeloid Leukemia (AML)
n=23 Participants
Patients receive 30 mg oral cediranib maleate QD on days 1-28. Treatment repeats every 28 days for up to 26 courses in the absence of disease progression or unacceptable toxicity.
|
Myelodysplastic Syndrome (MDS)
n=16 Participants
Patients receive 30 mg oral cediranib maleate QD on days 1-28. Treatment repeats every 28 days for up to 26 courses in the absence of disease progression or unacceptable toxicity.
|
Total
n=39 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
70 years
n=99 Participants
|
73 years
n=107 Participants
|
72 years
n=206 Participants
|
|
Gender
Female
|
12 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
18 Participants
n=206 Participants
|
|
Gender
Male
|
11 Participants
n=99 Participants
|
10 Participants
n=107 Participants
|
21 Participants
n=206 Participants
|
|
Region of Enrollment
United States
|
23 participants
n=99 Participants
|
16 participants
n=107 Participants
|
39 participants
n=206 Participants
|
PRIMARY outcome
Timeframe: At the end of cycles 1 and 3 and every 3 cycles thereafter up to 26 cyclesPopulation: All participants were evaluable for this endpoint.
Complete Response (CR) requires a repeat bone marrow with \< 5% myeloblasts, hemoglobin ≥ 11 g/dl, neutrophils ≥ 1000/mm3, platelets ≥ 100,000/mm3, and no circulating blasts. Partial Response (PR) requires a bone marrow blast reduction of 50% or more, hemoglobin ≥ 11 g/dl, neutrophils ≥ 1000/mm3, platelets ≥ 100,000/mm3, and no circulating blasts. Hematologic Improvement (HI) requires one of the following: 1. RBC transfusion independent participants are required to have \>1.5 g/dL increase in hemoglobin, 2. RBC transfusion-dependent participants are required to be transfusion independent, 3. A 100% increase, and an absolute increase over 500mm\^3 in Absolute Neutrophil Count, 4. Participants with a pretreatment platelet count over 20,000/mm3 require an absolute increase of 30,000/mm\^3 or more, 5. Participants with platelet count below 20,000/mm3 require an increase over 20,000/mm\^3 and by at least 100%.
Outcome measures
| Measure |
Acute Myeloid Leukemia (AML)
n=23 Participants
Patients receive 30 mg oral cediranib maleate QD on days 1-28. Treatment repeats every 28 days for up to 26 courses in the absence of disease progression or unacceptable toxicity.
|
Myelodysplastic Syndrome (MDS)
n=16 Participants
Patients receive 30 mg oral cediranib maleate QD on days 1-28. Treatment repeats every 28 days for up to 26 courses in the absence of disease progression or unacceptable toxicity.
|
|---|---|---|
|
The Number of Confirmed Disease Response: Complete Response (CR), Partial Response (PR), and Hematologic Improvement (HI). A Confirmed Response is Defined to be an Objective Status of CR, PR, or HI Noted on 2 Consecutive Evaluations.
Partial Response (PR)
|
0 participants
|
0 participants
|
|
The Number of Confirmed Disease Response: Complete Response (CR), Partial Response (PR), and Hematologic Improvement (HI). A Confirmed Response is Defined to be an Objective Status of CR, PR, or HI Noted on 2 Consecutive Evaluations.
Complete Response (CR)
|
0 participants
|
0 participants
|
|
The Number of Confirmed Disease Response: Complete Response (CR), Partial Response (PR), and Hematologic Improvement (HI). A Confirmed Response is Defined to be an Objective Status of CR, PR, or HI Noted on 2 Consecutive Evaluations.
Hematologic Improvement
|
0 participants
|
1 participants
|
SECONDARY outcome
Timeframe: Every cycle during treatment and every 6 months for up to 2 years after completion of study treatmentPopulation: All participants were evaluable for this endpoint.
Defined as the time from date of registration to date of death due to any cause or date last known alive. The distribution of survival time will be estimated using the method of Kaplan-Meier.
Outcome measures
| Measure |
Acute Myeloid Leukemia (AML)
n=23 Participants
Patients receive 30 mg oral cediranib maleate QD on days 1-28. Treatment repeats every 28 days for up to 26 courses in the absence of disease progression or unacceptable toxicity.
|
Myelodysplastic Syndrome (MDS)
n=16 Participants
Patients receive 30 mg oral cediranib maleate QD on days 1-28. Treatment repeats every 28 days for up to 26 courses in the absence of disease progression or unacceptable toxicity.
|
|---|---|---|
|
Overall Survival
|
3.71 months
Interval 2.2 to 5.75
|
4.66 months
Interval 1.97 to 10.81
|
SECONDARY outcome
Timeframe: Every 3 courses during treatment and then at 3 months and every 6 months for up to 2 years after completion of study treatmentPopulation: All participants are evaluable for this primary endpoint.
Defined as the time from date of registration to date that disease progression was documented, death, or last date that progression-free status was documented, whichever comes first. Estimated using the method of Kaplan-Meier. Disease progression is defined as one of the following: * A ≥ 50% increase in bone marrow blasts from the best response, or * A 50% or greater decrement from maximum remission/response levels in neutrophils or platelets, or * A reduction in hemoglobin concentration by at least 1.5 g/dl, or * Transfusion dependence (without alternative explanation and sustained for at least 2 weeks).
Outcome measures
| Measure |
Acute Myeloid Leukemia (AML)
n=23 Participants
Patients receive 30 mg oral cediranib maleate QD on days 1-28. Treatment repeats every 28 days for up to 26 courses in the absence of disease progression or unacceptable toxicity.
|
Myelodysplastic Syndrome (MDS)
n=16 Participants
Patients receive 30 mg oral cediranib maleate QD on days 1-28. Treatment repeats every 28 days for up to 26 courses in the absence of disease progression or unacceptable toxicity.
|
|---|---|---|
|
Progression-free Survival
|
2.82 months
Interval 1.15 to 5.35
|
4.30 months
Interval 1.97 to 7.72
|
SECONDARY outcome
Timeframe: Every 3 courses up to 26 coursesPopulation: This endpoint was not analyzed due to lack of response.
Measured from the time criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented. Estimated using the method of Kaplan-Meier.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Continuously during treatment up to 26 coursesPopulation: All participants were analyzed for this endpoint.
Graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. All adverse events determined to be possibly, probably, or definately related to AZD2171 are included in this analysis.
Outcome measures
| Measure |
Acute Myeloid Leukemia (AML)
n=23 Participants
Patients receive 30 mg oral cediranib maleate QD on days 1-28. Treatment repeats every 28 days for up to 26 courses in the absence of disease progression or unacceptable toxicity.
|
Myelodysplastic Syndrome (MDS)
n=16 Participants
Patients receive 30 mg oral cediranib maleate QD on days 1-28. Treatment repeats every 28 days for up to 26 courses in the absence of disease progression or unacceptable toxicity.
|
|---|---|---|
|
The Number of Patients That Report Adverse Events Possibly, Probably, or Definitely Related to AZD2171.
Grade 3 or Higher
|
14 participants
|
11 participants
|
|
The Number of Patients That Report Adverse Events Possibly, Probably, or Definitely Related to AZD2171.
Grade 4 or Higher
|
7 participants
|
5 participants
|
|
The Number of Patients That Report Adverse Events Possibly, Probably, or Definitely Related to AZD2171.
Grade 5
|
0 participants
|
0 participants
|
Adverse Events
All Patients Receiving Cediranib Maleate
Serious adverse events
| Measure |
All Patients Receiving Cediranib Maleate
n=39 participants at risk
All patients receiving oral cediranib maleate, regardless of diagnosis were analyzed for toxicity.
|
|---|---|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
5.1%
2/39 • Number of events 2
|
|
Blood and lymphatic system disorders
Hemoglobin decreased
|
10.3%
4/39 • Number of events 6
|
|
Gastrointestinal disorders
Diarrhea
|
5.1%
2/39 • Number of events 2
|
|
Gastrointestinal disorders
Dyspepsia
|
2.6%
1/39 • Number of events 2
|
|
Gastrointestinal disorders
Lower gastrointestinal hemorrhage
|
5.1%
2/39 • Number of events 2
|
|
Gastrointestinal disorders
Mucositis oral
|
2.6%
1/39 • Number of events 1
|
|
Gastrointestinal disorders
Upper gastrointestinal hemorrhage
|
2.6%
1/39 • Number of events 1
|
|
General disorders
Fatigue
|
17.9%
7/39 • Number of events 7
|
|
Infections and infestations
Infection
|
2.6%
1/39 • Number of events 1
|
|
Infections and infestations
Pneumonia
|
5.1%
2/39 • Number of events 2
|
|
Infections and infestations
Sepsis
|
2.6%
1/39 • Number of events 1
|
|
Infections and infestations
Urinary tract infection
|
2.6%
1/39 • Number of events 2
|
|
Investigations
INR increased
|
2.6%
1/39 • Number of events 1
|
|
Investigations
Leukocyte count decreased
|
7.7%
3/39 • Number of events 4
|
|
Investigations
Lymphocyte count decreased
|
2.6%
1/39 • Number of events 1
|
|
Investigations
Neutrophil count decreased
|
17.9%
7/39 • Number of events 10
|
|
Investigations
Platelet count decreased
|
20.5%
8/39 • Number of events 10
|
|
Investigations
Weight loss
|
2.6%
1/39 • Number of events 1
|
|
Metabolism and nutrition disorders
Anorexia
|
2.6%
1/39 • Number of events 1
|
|
Metabolism and nutrition disorders
Dehydration
|
2.6%
1/39 • Number of events 1
|
|
Metabolism and nutrition disorders
Serum potassium decreased
|
5.1%
2/39 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Chest wall pain
|
2.6%
1/39 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Joint pain
|
2.6%
1/39 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness
|
5.1%
2/39 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness lower limb
|
2.6%
1/39 • Number of events 1
|
|
Nervous system disorders
Intracranial hemorrhage
|
2.6%
1/39 • Number of events 1
|
|
Renal and urinary disorders
Bladder hemorrhage
|
2.6%
1/39 • Number of events 1
|
|
Renal and urinary disorders
Protein urine positive
|
5.1%
2/39 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
10.3%
4/39 • Number of events 4
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
2.6%
1/39 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Petechiae
|
2.6%
1/39 • Number of events 1
|
|
Vascular disorders
Hypertension
|
7.7%
3/39 • Number of events 3
|
|
Vascular disorders
Hypotension
|
2.6%
1/39 • Number of events 1
|
Other adverse events
| Measure |
All Patients Receiving Cediranib Maleate
n=39 participants at risk
All patients receiving oral cediranib maleate, regardless of diagnosis were analyzed for toxicity.
|
|---|---|
|
Blood and lymphatic system disorders
Hemoglobin decreased
|
7.7%
3/39 • Number of events 3
|
|
Cardiac disorders
Atrial fibrillation
|
2.6%
1/39 • Number of events 1
|
|
Cardiac disorders
Left ventricular failure
|
2.6%
1/39 • Number of events 1
|
|
Endocrine disorders
Hypothyroidism
|
5.1%
2/39 • Number of events 3
|
|
Gastrointestinal disorders
Constipation
|
15.4%
6/39 • Number of events 6
|
|
Gastrointestinal disorders
Diarrhea
|
53.8%
21/39 • Number of events 49
|
|
Gastrointestinal disorders
Dry mouth
|
2.6%
1/39 • Number of events 1
|
|
Gastrointestinal disorders
Dyspepsia
|
2.6%
1/39 • Number of events 1
|
|
Gastrointestinal disorders
Ear, nose and throat examination abnormal
|
5.1%
2/39 • Number of events 2
|
|
Gastrointestinal disorders
Lower gastrointestinal hemorrhage
|
10.3%
4/39 • Number of events 4
|
|
Gastrointestinal disorders
Mucositis oral
|
5.1%
2/39 • Number of events 2
|
|
Gastrointestinal disorders
Nausea
|
41.0%
16/39 • Number of events 22
|
|
Gastrointestinal disorders
Oral pain
|
2.6%
1/39 • Number of events 1
|
|
Gastrointestinal disorders
Rectal pain
|
2.6%
1/39 • Number of events 1
|
|
Gastrointestinal disorders
Vomiting
|
12.8%
5/39 • Number of events 9
|
|
General disorders
Edema limbs
|
12.8%
5/39 • Number of events 7
|
|
General disorders
Fatigue
|
89.7%
35/39 • Number of events 66
|
|
Infections and infestations
Bladder infection
|
2.6%
1/39 • Number of events 1
|
|
Infections and infestations
Colitis, infectious (e.g., Clostridium difficile)
|
2.6%
1/39 • Number of events 1
|
|
Infections and infestations
Skin infection
|
2.6%
1/39 • Number of events 2
|
|
Infections and infestations
Upper respiratory infection
|
2.6%
1/39 • Number of events 1
|
|
Infections and infestations
Urinary tract infection
|
2.6%
1/39 • Number of events 1
|
|
Injury, poisoning and procedural complications
Bruising
|
10.3%
4/39 • Number of events 4
|
|
Investigations
Alanine aminotransferase increased
|
2.6%
1/39 • Number of events 3
|
|
Investigations
Alkaline phosphatase increased
|
2.6%
1/39 • Number of events 1
|
|
Investigations
Aspartate aminotransferase increased
|
2.6%
1/39 • Number of events 1
|
|
Investigations
Bilirubin increased
|
2.6%
1/39 • Number of events 1
|
|
Investigations
Creatinine increased
|
5.1%
2/39 • Number of events 4
|
|
Investigations
INR increased
|
2.6%
1/39 • Number of events 2
|
|
Investigations
Laboratory test abnormal
|
2.6%
1/39 • Number of events 1
|
|
Investigations
Leukocyte count decreased
|
7.7%
3/39 • Number of events 3
|
|
Investigations
Neutrophil count decreased
|
30.8%
12/39 • Number of events 18
|
|
Investigations
Platelet count decreased
|
48.7%
19/39 • Number of events 36
|
|
Investigations
Weight loss
|
33.3%
13/39 • Number of events 23
|
|
Metabolism and nutrition disorders
Anorexia
|
17.9%
7/39 • Number of events 9
|
|
Metabolism and nutrition disorders
Blood glucose increased
|
7.7%
3/39 • Number of events 7
|
|
Metabolism and nutrition disorders
Dehydration
|
2.6%
1/39 • Number of events 2
|
|
Metabolism and nutrition disorders
Serum phosphate decreased
|
2.6%
1/39 • Number of events 3
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
5.1%
2/39 • Number of events 5
|
|
Musculoskeletal and connective tissue disorders
Chest wall pain
|
2.6%
1/39 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Joint pain
|
2.6%
1/39 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness
|
28.2%
11/39 • Number of events 16
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
2.6%
1/39 • Number of events 1
|
|
Nervous system disorders
Ataxia
|
2.6%
1/39 • Number of events 1
|
|
Nervous system disorders
Dizziness
|
28.2%
11/39 • Number of events 15
|
|
Nervous system disorders
Headache
|
25.6%
10/39 • Number of events 15
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
7.7%
3/39 • Number of events 6
|
|
Renal and urinary disorders
Hemorrhage urinary tract
|
2.6%
1/39 • Number of events 1
|
|
Renal and urinary disorders
Protein urine positive
|
48.7%
19/39 • Number of events 26
|
|
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis
|
2.6%
1/39 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
2.6%
1/39 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
69.2%
27/39 • Number of events 56
|
|
Respiratory, thoracic and mediastinal disorders
Hemorrhage nasal
|
5.1%
2/39 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
2.6%
1/39 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Voice alteration
|
20.5%
8/39 • Number of events 13
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
2.6%
1/39 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Sweating
|
2.6%
1/39 • Number of events 1
|
|
Vascular disorders
Hypertension
|
64.1%
25/39 • Number of events 40
|
|
Vascular disorders
Hypotension
|
5.1%
2/39 • Number of events 2
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60