Trial Outcomes & Findings for Avelumab and Azacitidine in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia (NCT NCT02953561)
NCT ID: NCT02953561
Last Updated: 2020-10-22
Results Overview
Complete Response (CR) + Partial Remission (PR) + Complete Remission with incomplete recovery (CRi) + Clinical Benefit. CR = normalization of peripheral blood (PB) and bone marrow (BM) with \</= 5% BM blasts, PB granulocyte count \>/= (1.0 x 10\^9/L, and a platelet count \>/= 100 x 10\^9/L). PR = same as CR except presence of 6-15% marrow blasts, or 50% reduction if \<15% at start of treatment. CRi meets all criteria for CR except for platelet recovery to \>100 x 10\^9/L and/or granulocyte count \> (1.0 x 10\^9/L). MLFS is BM with \</= 5% BM blasts with no PB recovery. Hematologic Improvement is platelets increase by \>/= 30 x 10\^9/L untransfused (if \<20 at pretherapy); or granulocytes increase by 100% and to \>0.5 x 10\^9/L (if lower than that pre-therapy); or hemoglobin increase by 2 g/dl; or transfusion independent; or splenomegaly reduction by \> 50%; or monocytosis reduction by \> 50% if pretreatment \> 5 x 109/L, or BM or PB Blasts decrease by \>/= 50%.
TERMINATED
PHASE1/PHASE2
19 participants
Up to 2 years
2020-10-22
Participant Flow
Recruitment Period: February 2017 to February 2019
Participant milestones
| Measure |
Treatment (Azacitidine, Avelumab)
Patients receive azacitidine SC or IV over 10-40 minutes on days 1-7 or on days 1-5 and 8-9. Patients also receive avelumab IV over 60 minutes on days 1 and 14 for 4 courses (or until complete response) and on day 1 for subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Avelumab: Given IV
Azacitidine: Given subcutaneous or IV
Laboratory Biomarker Analysis: Correlative studies
|
|---|---|
|
Overall Study
STARTED
|
19
|
|
Overall Study
COMPLETED
|
19
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Avelumab and Azacitidine in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia
Baseline characteristics by cohort
| Measure |
Treatment (Azacitidine, Avelumab)
n=19 Participants
Patients receive azacitidine SC or IV over 10-40 minutes on days 1-7 or on days 1-5 and 8-9. Patients also receive avelumab IV over 60 minutes on days 1 and 14 for 4 courses (or until complete response) and on day 1 for subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Avelumab: Given IV
Azacitidine: Given SC or IV
Laboratory Biomarker Analysis: Correlative studies
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
8 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
11 Participants
n=5 Participants
|
|
Age, Continuous
|
69 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
15 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
19 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 2 yearsPopulation: Of the 19 participants registered, 17 participants were evaluable for response.
Complete Response (CR) + Partial Remission (PR) + Complete Remission with incomplete recovery (CRi) + Clinical Benefit. CR = normalization of peripheral blood (PB) and bone marrow (BM) with \</= 5% BM blasts, PB granulocyte count \>/= (1.0 x 10\^9/L, and a platelet count \>/= 100 x 10\^9/L). PR = same as CR except presence of 6-15% marrow blasts, or 50% reduction if \<15% at start of treatment. CRi meets all criteria for CR except for platelet recovery to \>100 x 10\^9/L and/or granulocyte count \> (1.0 x 10\^9/L). MLFS is BM with \</= 5% BM blasts with no PB recovery. Hematologic Improvement is platelets increase by \>/= 30 x 10\^9/L untransfused (if \<20 at pretherapy); or granulocytes increase by 100% and to \>0.5 x 10\^9/L (if lower than that pre-therapy); or hemoglobin increase by 2 g/dl; or transfusion independent; or splenomegaly reduction by \> 50%; or monocytosis reduction by \> 50% if pretreatment \> 5 x 109/L, or BM or PB Blasts decrease by \>/= 50%.
Outcome measures
| Measure |
Treatment (Azacitidine, Avelumab)
n=17 Participants
Patients receive azacitidine SC or IV over 10-40 minutes on days 1-7 or on days 1-5 and 8-9. Patients also receive avelumab IV over 60 minutes on days 1 and 14 for 4 courses (or until complete response) and on day 1 for subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Avelumab: Given IV
Azacitidine: Given SC or IV
Laboratory Biomarker Analysis: Correlative studies
|
|---|---|
|
Number of Participants With a Response
|
4 Participants
|
SECONDARY outcome
Timeframe: Up to 1 yearTime from date of treatment start until the date of first objective documentation of disease-relapse.
Outcome measures
| Measure |
Treatment (Azacitidine, Avelumab)
n=17 Participants
Patients receive azacitidine SC or IV over 10-40 minutes on days 1-7 or on days 1-5 and 8-9. Patients also receive avelumab IV over 60 minutes on days 1 and 14 for 4 courses (or until complete response) and on day 1 for subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Avelumab: Given IV
Azacitidine: Given SC or IV
Laboratory Biomarker Analysis: Correlative studies
|
|---|---|
|
Disease-free Survival
|
8.2 Months
Interval 6.5 to 9.8
|
SECONDARY outcome
Timeframe: Up to 1 yearDistribution of OS will be estimated using the method of Kaplan and Meier. Comparisons of time-to-event endpoints by important subgroups will be made using the log-rank tests.
Outcome measures
| Measure |
Treatment (Azacitidine, Avelumab)
n=17 Participants
Patients receive azacitidine SC or IV over 10-40 minutes on days 1-7 or on days 1-5 and 8-9. Patients also receive avelumab IV over 60 minutes on days 1 and 14 for 4 courses (or until complete response) and on day 1 for subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Avelumab: Given IV
Azacitidine: Given SC or IV
Laboratory Biomarker Analysis: Correlative studies
|
|---|---|
|
Overall Survival (OS)
|
4.7 Months
Interval 0.1 to 11.0
|
SECONDARY outcome
Timeframe: Up to 1 yearDistribution of PFS will be estimated using the method of Kaplan and Meier. Comparisons of time-to-event endpoints by important subgroups will be made using the log-rank tests.
Outcome measures
| Measure |
Treatment (Azacitidine, Avelumab)
n=17 Participants
Patients receive azacitidine SC or IV over 10-40 minutes on days 1-7 or on days 1-5 and 8-9. Patients also receive avelumab IV over 60 minutes on days 1 and 14 for 4 courses (or until complete response) and on day 1 for subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Avelumab: Given IV
Azacitidine: Given SC or IV
Laboratory Biomarker Analysis: Correlative studies
|
|---|---|
|
Progression Free Survival (PFS)
|
3.2 Months
Interval 0.1 to 10.6
|
Adverse Events
Treatment (Azacitidine, Avelumab)
Serious adverse events
| Measure |
Treatment (Azacitidine, Avelumab)
n=19 participants at risk
Patients receive azacitidine SC or IV over 10-40 minutes on days 1-7 or on days 1-5 and 8-9. Patients also receive avelumab IV over 60 minutes on days 1 and 14 for 4 courses (or until complete response) and on day 1 for subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Avelumab: Given IV
Azacitidine: Given SC or IV
Laboratory Biomarker Analysis: Correlative studies
|
|---|---|
|
Infections and infestations
Anorectal Infection
|
10.5%
2/19 • Number of events 3 • Up to 1 year
|
|
Blood and lymphatic system disorders
Blood and Lymphatic System Disorders
|
5.3%
1/19 • Number of events 1 • Up to 1 year
|
|
General disorders
Death
|
5.3%
1/19 • Number of events 1 • Up to 1 year
|
|
Gastrointestinal disorders
Diarrhea
|
5.3%
1/19 • Number of events 1 • Up to 1 year
|
|
Gastrointestinal disorders
Dysphagia
|
5.3%
1/19 • Number of events 1 • Up to 1 year
|
|
Infections and infestations
Endocarditis
|
5.3%
1/19 • Number of events 1 • Up to 1 year
|
|
Infections and infestations
Neutropenic Fever
|
21.1%
4/19 • Number of events 4 • Up to 1 year
|
|
General disorders
Fever
|
5.3%
1/19 • Number of events 1 • Up to 1 year
|
|
Gastrointestinal disorders
Gastrointestinal disorders
|
5.3%
1/19 • Number of events 1 • Up to 1 year
|
|
Renal and urinary disorders
Hematuria
|
5.3%
1/19 • Number of events 1 • Up to 1 year
|
|
Metabolism and nutrition disorders
Hyponatremia
|
5.3%
1/19 • Number of events 1 • Up to 1 year
|
|
Vascular disorders
Hypotension
|
5.3%
1/19 • Number of events 1 • Up to 1 year
|
|
Infections and infestations
Infection
|
15.8%
3/19 • Number of events 6 • Up to 1 year
|
|
Infections and infestations
Lung Infection
|
31.6%
6/19 • Number of events 12 • Up to 1 year
|
|
Metabolism and nutrition disorders
Metabolism and Nutrition Disorder
|
5.3%
1/19 • Number of events 1 • Up to 1 year
|
|
General disorders
Pain
|
5.3%
1/19 • Number of events 1 • Up to 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Pleural Effusion
|
5.3%
1/19 • Number of events 2 • Up to 1 year
|
|
Infections and infestations
Pneumonitis
|
15.8%
3/19 • Number of events 3 • Up to 1 year
|
|
Infections and infestations
Sepsis
|
15.8%
3/19 • Number of events 4 • Up to 1 year
|
|
Infections and infestations
Skin Infection
|
5.3%
1/19 • Number of events 1 • Up to 1 year
|
|
Infections and infestations
Soft Tissue Infection
|
5.3%
1/19 • Number of events 1 • Up to 1 year
|
|
Nervous system disorders
Stroke
|
5.3%
1/19 • Number of events 1 • Up to 1 year
|
|
Nervous system disorders
Syncope
|
5.3%
1/19 • Number of events 1 • Up to 1 year
|
Other adverse events
| Measure |
Treatment (Azacitidine, Avelumab)
n=19 participants at risk
Patients receive azacitidine SC or IV over 10-40 minutes on days 1-7 or on days 1-5 and 8-9. Patients also receive avelumab IV over 60 minutes on days 1 and 14 for 4 courses (or until complete response) and on day 1 for subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Avelumab: Given IV
Azacitidine: Given SC or IV
Laboratory Biomarker Analysis: Correlative studies
|
|---|---|
|
Investigations
Elevated Alanine Aminotransferase Increase
|
10.5%
2/19 • Number of events 2 • Up to 1 year
|
|
Infections and infestations
Alkaline Phosphatase Increased
|
5.3%
1/19 • Number of events 1 • Up to 1 year
|
|
Blood and lymphatic system disorders
Anemia
|
10.5%
2/19 • Number of events 2 • Up to 1 year
|
|
Gastrointestinal disorders
Anorexia
|
15.8%
3/19 • Number of events 3 • Up to 1 year
|
|
Blood and lymphatic system disorders
Blood and Lymphatic System Disorders
|
5.3%
1/19 • Number of events 1 • Up to 1 year
|
|
Investigations
Blood Bilirubin Increased
|
5.3%
1/19 • Number of events 1 • Up to 1 year
|
|
Investigations
Cardiac Troponin I Increase
|
5.3%
1/19 • Number of events 1 • Up to 1 year
|
|
General disorders
Cbills
|
5.3%
1/19 • Number of events 1 • Up to 1 year
|
|
Psychiatric disorders
Confusion
|
15.8%
3/19 • Number of events 3 • Up to 1 year
|
|
Gastrointestinal disorders
Diarrhea
|
31.6%
6/19 • Number of events 6 • Up to 1 year
|
|
General disorders
Fatigue
|
21.1%
4/19 • Number of events 4 • Up to 1 year
|
|
Musculoskeletal and connective tissue disorders
Generalized Muscle Weakness
|
10.5%
2/19 • Number of events 2 • Up to 1 year
|
|
Nervous system disorders
Headache
|
5.3%
1/19 • Number of events 1 • Up to 1 year
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
5.3%
1/19 • Number of events 1 • Up to 1 year
|
|
Vascular disorders
Hypertension
|
10.5%
2/19 • Number of events 2 • Up to 1 year
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
5.3%
1/19 • Number of events 1 • Up to 1 year
|
|
Metabolism and nutrition disorders
hyponatremia
|
5.3%
1/19 • Number of events 1 • Up to 1 year
|
|
Endocrine disorders
Hypothyroidism
|
5.3%
1/19 • Number of events 1 • Up to 1 year
|
|
General disorders
Infusion Related Reaction
|
21.1%
4/19 • Number of events 5 • Up to 1 year
|
|
Investigations
Lymphocyte Count Decreased
|
10.5%
2/19 • Number of events 2 • Up to 1 year
|
|
Infections and infestations
Mucosal Infection
|
5.3%
1/19 • Number of events 1 • Up to 1 year
|
|
Gastrointestinal disorders
Oral Mucositis
|
21.1%
4/19 • Number of events 4 • Up to 1 year
|
|
Gastrointestinal disorders
Nausea
|
31.6%
6/19 • Number of events 6 • Up to 1 year
|
|
Investigations
Neutropenia
|
10.5%
2/19 • Number of events 2 • Up to 1 year
|
|
Blood and lymphatic system disorders
Neutropenic Fever
|
5.3%
1/19 • Number of events 1 • Up to 1 year
|
|
Investigations
Platelet Count Decrease
|
5.3%
1/19 • Number of events 1 • Up to 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Pleural Effusion
|
10.5%
2/19 • Number of events 2 • Up to 1 year
|
|
Skin and subcutaneous tissue disorders
Rash
|
10.5%
2/19 • Number of events 2 • Up to 1 year
|
|
Gastrointestinal disorders
Vomiting
|
36.8%
7/19 • Number of events 8 • Up to 1 year
|
|
Investigations
White Blood Count Decreased
|
10.5%
2/19 • Number of events 3 • Up to 1 year
|
Additional Information
Naval Daver MD./Associate Professor
The University of Texas MD Anderson Cancer Center
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place