Trial Outcomes & Findings for Phase 2 Study of Temozolomide to Treat Poor Risk / Refractory Acute Myeloid Leukemia (NCT NCT00611247)
NCT ID: NCT00611247
Last Updated: 2018-06-15
Results Overview
Response determined per European LeukemiaNet response criteria: CR = bone marrow blasts \<5%; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count \> 1.0 x 10e9/L; platelet count \> 100 x 10e9/L; and independence of red cell transfusions. CRi = all CR criteria except for residual neutropenia (\< 1.0 x 10e9/L) or thrombocytopenia (\< 100 x 10e9/L)\]. Morphologic leukemia-free state (LFS) = bone marrow blasts \<5%; absence of blasts with Auer rods; absence of extramedullary disease; with no hematologic recovery required. Relapse = bone marrow blasts \>5%; reappearance of blasts in the blood; or development of extramedullary disease.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
42 participants
Primary outcome timeframe
up to 2 months
Results posted on
2018-06-15
Participant Flow
42 subjects consented to screening for this study.
6 of 42 subjects did not meet eligibility criteria and did not receive induction therapy. Of these, 1 subject had no evidence of AML; 1 had acute lymphoblastic leukemia, and 4 had disease progression and death before induction. None of the 6 were stratified to a treatment group, and were not treated on study.
Participant milestones
| Measure |
Methylated AGAT Promoter (Group 1)
Induction: 200 mg/m2/day oral Temozolomide x 7 days
|
Un-Methylated AGAT Promoter (Group 2)
Priming: 100 mg/m2/day oral Temozolomide x 14 days, followed by Induction: 200 mg/m2/day oral Temozolomide x 7 days
|
|---|---|---|
|
Overall Study
STARTED
|
5
|
31
|
|
Overall Study
COMPLETED
|
3
|
10
|
|
Overall Study
NOT COMPLETED
|
2
|
21
|
Reasons for withdrawal
| Measure |
Methylated AGAT Promoter (Group 1)
Induction: 200 mg/m2/day oral Temozolomide x 7 days
|
Un-Methylated AGAT Promoter (Group 2)
Priming: 100 mg/m2/day oral Temozolomide x 14 days, followed by Induction: 200 mg/m2/day oral Temozolomide x 7 days
|
|---|---|---|
|
Overall Study
Death
|
1
|
5
|
|
Overall Study
Lack of Efficacy
|
1
|
16
|
Baseline Characteristics
Phase 2 Study of Temozolomide to Treat Poor Risk / Refractory Acute Myeloid Leukemia
Baseline characteristics by cohort
| Measure |
Methylated AGAT Promoter (Group 1)
n=5 Participants
Induction: 200 mg/m2/day oral Temozolomide x 7 days
|
Un-Methylated AGAT Promoter (Group 2)
n=31 Participants
Priming: 100 mg/m2/day oral Temozolomide x 14 days, followed by Induction: 200 mg/m2/day oral Temozolomide x 7 days
|
Total
n=36 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
77 years
n=93 Participants
|
75 years
n=4 Participants
|
75 years
n=27 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=93 Participants
|
11 Participants
n=4 Participants
|
13 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=93 Participants
|
20 Participants
n=4 Participants
|
23 Participants
n=27 Participants
|
PRIMARY outcome
Timeframe: up to 2 monthsResponse determined per European LeukemiaNet response criteria: CR = bone marrow blasts \<5%; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count \> 1.0 x 10e9/L; platelet count \> 100 x 10e9/L; and independence of red cell transfusions. CRi = all CR criteria except for residual neutropenia (\< 1.0 x 10e9/L) or thrombocytopenia (\< 100 x 10e9/L)\]. Morphologic leukemia-free state (LFS) = bone marrow blasts \<5%; absence of blasts with Auer rods; absence of extramedullary disease; with no hematologic recovery required. Relapse = bone marrow blasts \>5%; reappearance of blasts in the blood; or development of extramedullary disease.
Outcome measures
| Measure |
Methylated AGAT Promoter (Group 1)
n=5 Participants
Induction: 200 mg/m2/day oral Temozolomide x 7 days
|
Un-Methylated AGAT Promoter (Group 2)
n=31 Participants
Priming: 100 mg/m2/day oral Temozolomide x 14 days, followed by Induction: 200 mg/m2/day oral Temozolomide x 7 days
|
|---|---|---|
|
Response Rate (CR + CRi + LFS)
|
3 participants
|
10 participants
|
SECONDARY outcome
Timeframe: 12 monthsOutcome measures
| Measure |
Methylated AGAT Promoter (Group 1)
n=5 Participants
Induction: 200 mg/m2/day oral Temozolomide x 7 days
|
Un-Methylated AGAT Promoter (Group 2)
n=31 Participants
Priming: 100 mg/m2/day oral Temozolomide x 14 days, followed by Induction: 200 mg/m2/day oral Temozolomide x 7 days
|
|---|---|---|
|
Toxicity Profile: Total Number of Drug-related Serious Adverse Events
|
4 events
|
27 events
|
SECONDARY outcome
Timeframe: 12 monthsOutcome measures
| Measure |
Methylated AGAT Promoter (Group 1)
n=5 Participants
Induction: 200 mg/m2/day oral Temozolomide x 7 days
|
Un-Methylated AGAT Promoter (Group 2)
n=31 Participants
Priming: 100 mg/m2/day oral Temozolomide x 14 days, followed by Induction: 200 mg/m2/day oral Temozolomide x 7 days
|
|---|---|---|
|
Toxicity Profile: Individual Subjects With Drug-related SAEs
|
4 participants
|
13 participants
|
Adverse Events
Methylated AGAT Promoter (Group 1)
Serious events: 4 serious events
Other events: 3 other events
Deaths: 0 deaths
Un-Methylated AGAT Promoter (Group 2)
Serious events: 28 serious events
Other events: 23 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Methylated AGAT Promoter (Group 1)
n=5 participants at risk
Induction: 200 mg/m2/day oral Temozolomide x 7 days
|
Un-Methylated AGAT Promoter (Group 2)
n=31 participants at risk
Priming: 100 mg/m2/day oral Temozolomide x 14 days, then followed by Induction: 200 mg/m2/day oral Temozolomide x 7 days
|
|---|---|---|
|
Blood and lymphatic system disorders
Anemia
|
20.0%
1/5 • Number of events 1
|
3.2%
1/31 • Number of events 1
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
80.0%
4/5 • Number of events 5
|
41.9%
13/31 • Number of events 21
|
|
Blood and lymphatic system disorders
Blood and lymphatic system disorders - Other, Pancytopenia
|
0.00%
0/5
|
3.2%
1/31 • Number of events 1
|
|
Cardiac disorders
Atrial fibrillation
|
20.0%
1/5 • Number of events 1
|
3.2%
1/31 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal pain
|
20.0%
1/5 • Number of events 1
|
3.2%
1/31 • Number of events 1
|
|
Gastrointestinal disorders
Arthralgia
|
20.0%
1/5 • Number of events 1
|
0.00%
0/31
|
|
Gastrointestinal disorders
Rectal hemorrhage
|
0.00%
0/5
|
3.2%
1/31 • Number of events 1
|
|
General disorders
Multi-organ failure
|
0.00%
0/5
|
3.2%
1/31 • Number of events 1
|
|
General disorders
Sudden death NOS
|
0.00%
0/5
|
6.5%
2/31 • Number of events 2
|
|
General disorders
Death NOS
|
20.0%
1/5 • Number of events 1
|
9.7%
3/31 • Number of events 3
|
|
Infections and infestations
Mucosa infection
|
0.00%
0/5
|
3.2%
1/31 • Number of events 1
|
|
Infections and infestations
Sepsis
|
0.00%
0/5
|
6.5%
2/31 • Number of events 2
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/5
|
3.2%
1/31 • Number of events 1
|
|
Investigations
Creatinine increased
|
0.00%
0/5
|
3.2%
1/31 • Number of events 1
|
|
Investigations
Platelet count decreased
|
20.0%
1/5 • Number of events 2
|
32.3%
10/31 • Number of events 14
|
|
Metabolism and nutrition disorders
Hyponatremia
|
0.00%
0/5
|
3.2%
1/31 • Number of events 1
|
|
Nervous system disorders
Depressed level of consciousness
|
0.00%
0/5
|
3.2%
1/31 • Number of events 1
|
|
Renal and urinary disorders
Urinary tract infection
|
0.00%
0/5
|
3.2%
1/31 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
0.00%
0/5
|
3.2%
1/31 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary fibrosis
|
0.00%
0/5
|
3.2%
1/31 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders - Other, fever/pneumonia
|
0.00%
0/5
|
3.2%
1/31 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders - Other, Multilobar pneumonia
|
0.00%
0/5
|
3.2%
1/31 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other, Rash
|
0.00%
0/5
|
3.2%
1/31 • Number of events 1
|
|
Vascular disorders
Hypotension
|
0.00%
0/5
|
3.2%
1/31 • Number of events 1
|
|
Blood and lymphatic system disorders
Hypoalbuminemia
|
0.00%
0/5
|
3.2%
1/31 • Number of events 1
|
|
Gastrointestinal disorders
Oral Pain
|
20.0%
1/5 • Number of events 1
|
0.00%
0/31
|
|
Investigations
Neutrophil count decreased
|
20.0%
1/5 • Number of events 3
|
38.7%
12/31 • Number of events 17
|
|
Investigations
White blood cell decreased
|
20.0%
1/5 • Number of events 3
|
19.4%
6/31 • Number of events 6
|
Other adverse events
| Measure |
Methylated AGAT Promoter (Group 1)
n=5 participants at risk
Induction: 200 mg/m2/day oral Temozolomide x 7 days
|
Un-Methylated AGAT Promoter (Group 2)
n=31 participants at risk
Priming: 100 mg/m2/day oral Temozolomide x 14 days, then followed by Induction: 200 mg/m2/day oral Temozolomide x 7 days
|
|---|---|---|
|
Blood and lymphatic system disorders
Anemia
|
40.0%
2/5 • Number of events 5
|
61.3%
19/31 • Number of events 36
|
|
Blood and lymphatic system disorders
Blood and lymphatic system disorders - Not otherwise specified
|
20.0%
1/5 • Number of events 1
|
3.2%
1/31 • Number of events 2
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
20.0%
1/5 • Number of events 1
|
9.7%
3/31 • Number of events 3
|
|
Blood and lymphatic system disorders
Lymph node pain
|
20.0%
1/5 • Number of events 1
|
0.00%
0/31
|
|
Blood and lymphatic system disorders
Hemolysis
|
0.00%
0/5
|
6.5%
2/31 • Number of events 2
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/5
|
6.5%
2/31 • Number of events 2
|
|
Cardiac disorders
Cardiac disorders - Not otherwise specified
|
20.0%
1/5 • Number of events 1
|
3.2%
1/31 • Number of events 1
|
|
Eye disorders
Eye disorders - Not otherwise specified
|
20.0%
1/5 • Number of events 1
|
0.00%
0/31
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/5
|
9.7%
3/31 • Number of events 4
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/5
|
16.1%
5/31 • Number of events 8
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/5
|
25.8%
8/31 • Number of events 11
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/5
|
19.4%
6/31 • Number of events 7
|
|
Gastrointestinal disorders
Mucositis oral
|
0.00%
0/5
|
9.7%
3/31 • Number of events 3
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/5
|
32.3%
10/31 • Number of events 13
|
|
Gastrointestinal disorders
Rectal hemorrhage
|
0.00%
0/5
|
6.5%
2/31 • Number of events 2
|
|
Gastrointestinal disorders
Rectal Pain
|
0.00%
0/5
|
6.5%
2/31 • Number of events 2
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/5
|
16.1%
5/31 • Number of events 7
|
|
General disorders
Edema limbs
|
0.00%
0/5
|
19.4%
6/31 • Number of events 11
|
|
General disorders
Fatigue
|
60.0%
3/5 • Number of events 7
|
61.3%
19/31 • Number of events 24
|
|
General disorders
Fever
|
20.0%
1/5 • Number of events 3
|
6.5%
2/31 • Number of events 2
|
|
General disorders
Localized edema
|
20.0%
1/5 • Number of events 1
|
0.00%
0/31
|
|
General disorders
Pain
|
0.00%
0/5
|
9.7%
3/31 • Number of events 4
|
|
Infections and infestations
Lip infection
|
20.0%
1/5 • Number of events 1
|
0.00%
0/31
|
|
Infections and infestations
Infections and infestations - Not otherwise specified
|
0.00%
0/5
|
12.9%
4/31 • Number of events 5
|
|
Injury, poisoning and procedural complications
Bruising
|
0.00%
0/5
|
6.5%
2/31 • Number of events 2
|
|
Investigations
Activated partial thromboplastin time prolonged
|
20.0%
1/5 • Number of events 2
|
0.00%
0/31
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/5
|
12.9%
4/31 • Number of events 7
|
|
Investigations
Alkaline phosphatase increased
|
20.0%
1/5 • Number of events 2
|
12.9%
4/31 • Number of events 4
|
|
Investigations
Blood bilirubin increased
|
20.0%
1/5 • Number of events 1
|
0.00%
0/31
|
|
Investigations
Creatinine increased
|
40.0%
2/5 • Number of events 4
|
25.8%
8/31 • Number of events 11
|
|
Investigations
Neutrophil count decreased
|
20.0%
1/5 • Number of events 1
|
9.7%
3/31 • Number of events 7
|
|
Investigations
Platelet count decreased
|
20.0%
1/5 • Number of events 2
|
41.9%
13/31 • Number of events 19
|
|
Investigations
Weight loss
|
20.0%
1/5 • Number of events 1
|
12.9%
4/31 • Number of events 4
|
|
Investigations
White blood cell decreased
|
20.0%
1/5 • Number of events 2
|
29.0%
9/31 • Number of events 19
|
|
Metabolism and nutrition disorders
Anorexia
|
20.0%
1/5 • Number of events 2
|
25.8%
8/31 • Number of events 9
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
40.0%
2/5 • Number of events 5
|
41.9%
13/31 • Number of events 18
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
40.0%
2/5 • Number of events 4
|
32.3%
10/31 • Number of events 17
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
20.0%
1/5 • Number of events 2
|
16.1%
5/31 • Number of events 5
|
|
Metabolism and nutrition disorders
Hypokalemia
|
20.0%
1/5 • Number of events 4
|
0.00%
0/31
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
20.0%
1/5 • Number of events 1
|
6.5%
2/31 • Number of events 2
|
|
Metabolism and nutrition disorders
Hyponatremia
|
20.0%
1/5 • Number of events 2
|
22.6%
7/31 • Number of events 9
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/5
|
9.7%
3/31 • Number of events 3
|
|
Nervous system disorders
Dizziness
|
0.00%
0/5
|
9.7%
3/31 • Number of events 3
|
|
Nervous system disorders
Memory impairment
|
0.00%
0/5
|
6.5%
2/31 • Number of events 2
|
|
Nervous system disorders
Headache
|
20.0%
1/5 • Number of events 2
|
0.00%
0/31
|
|
Nervous system disorders
Syncope
|
20.0%
1/5 • Number of events 1
|
0.00%
0/31
|
|
Psychiatric disorders
Confusion
|
20.0%
1/5 • Number of events 1
|
0.00%
0/31
|
|
Psychiatric disorders
Depression
|
0.00%
0/5
|
9.7%
3/31 • Number of events 3
|
|
Psychiatric disorders
Insomnia
|
20.0%
1/5 • Number of events 1
|
3.2%
1/31 • Number of events 3
|
|
Renal and urinary disorders
Chronic kidney disease
|
20.0%
1/5 • Number of events 1
|
9.7%
3/31 • Number of events 3
|
|
Renal and urinary disorders
Urinary incontinence
|
0.00%
0/5
|
6.5%
2/31 • Number of events 2
|
|
Reproductive system and breast disorders
Vaginal hemorrhage
|
20.0%
1/5 • Number of events 1
|
0.00%
0/31
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
40.0%
2/5 • Number of events 3
|
19.4%
6/31 • Number of events 6
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
20.0%
1/5 • Number of events 2
|
9.7%
3/31 • Number of events 3
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
20.0%
1/5 • Number of events 1
|
6.5%
2/31 • Number of events 3
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
|
0.00%
0/5
|
6.5%
2/31 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/5
|
6.5%
2/31 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
20.0%
1/5 • Number of events 1
|
6.5%
2/31 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.00%
0/5
|
9.7%
3/31 • Number of events 5
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/5
|
6.5%
2/31 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Purpura
|
0.00%
0/5
|
16.1%
5/31 • Number of events 5
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
0.00%
0/5
|
6.5%
2/31 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Skin ulceration
|
0.00%
0/5
|
6.5%
2/31 • Number of events 2
|
|
Vascular disorders
Hypertension
|
0.00%
0/5
|
6.5%
2/31 • Number of events 2
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/5
|
6.5%
2/31 • 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