Trial Outcomes & Findings for Geriatric Assessment & Genetic Profiling to Personalize Therapy in Older Adults With Acute Myeloid Leukemia (NCT NCT03226418)
NCT ID: NCT03226418
Last Updated: 2025-11-05
Results Overview
All analyses will be performed based on intent-to-treat principle. The method of inversion will be used to generate an interval estimate for the proportion of 90-day mortality.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
75 participants
Primary outcome timeframe
At 90 days
Results posted on
2025-11-05
Participant Flow
2 participants ineligible
Participant milestones
| Measure |
Group I
INTENSIVE INDUCTION THERAPY: Patients receive cytarabine intravenously (IV) on days 1-7 and idarubicin over 10-15 minutes on days 1-3 (7+3), or liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1, 3 and 5. Gemtuzumab or midostaurin are added to 7+3 as per the standard of care. Treatment continues for 1 course in the absence of unacceptable toxicity.
INTENSIVE CONSOLIDATION THERAPY: Patients who go into remission, receive cytarabine IV over 1-3 hours twice daily (BID) on days 1, 3, and 5. Treatment repeats every 4 weeks for 2-4 courses in the absence of disease progression or unacceptable toxicity. Patients treated with liposome-encapsulated daunorubicin-cytarabine receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1 and 3. Treatment repeats every 5-8 weeks for 2 courses in the absence of disease progression, unacceptable toxicity.
Cytarabine: Given IV
Idarubicin: Given IV
Laboratory Biomarker Analysis: Correlative studies
Liposome-encapsulated Daunorubicin-Cytarabine: Given IV
Quality-of-Life Assessment: Ancillary studies
Questionnaire Administration: Ancillary studies
|
Group II
LOW-INTENSITY: Patients receive venetoclax in combination with azacitidine or decitabine or other standard of care low-intensity therapy such as azacitidine or decitabine alone or in combination with fms-like tyrosine kinase 3 (FLT3) inhibitor such as midostaurin, low-dose cytarabine in combination with glasdegib.
Venetoclax dose varies depending on drug interaction with antifungal agents. Given daily continuous for \>= 3 months orally. Glasdegib dose is 100 mg oral daily.
Decitabine IV over 1-3 hours daily for 5-10 days. Treatment repeats every 4-5 weeks for \>= 3 courses in the absence of disease progression, unacceptable toxicity or receipt of allogeneic stem cell transplant. Azacitidine IV infusion over 10 to 40 minutes days 1 -7. Treatment repeats every 4-5 weeks for \>= 3 courses in the absence of disease progression, unacceptable toxicity or receipt of allogeneic stem cell transplant.
Decitabine: Given IV
Laboratory Biomarker Analysis: Correlative studies
Quality-of-Life Assessment: Ancillary studies
Questionnaire Administration: Ancillary studies
Azacitidine: Given by infusion
Venetoclax: oral tablet
glasdegib: oral tablet
|
|---|---|---|
|
Overall Study
STARTED
|
8
|
65
|
|
Overall Study
COMPLETED
|
8
|
65
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Geriatric Assessment & Genetic Profiling to Personalize Therapy in Older Adults With Acute Myeloid Leukemia
Baseline characteristics by cohort
| Measure |
Group I
n=8 Participants
INTENSIVE INDUCTION THERAPY: Patients receive cytarabine intravenously (IV) on days 1-7 and idarubicin over 10-15 minutes on days 1-3 (7+3), or liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1, 3 and 5. Gemtuzumab or midostaurin are added to 7+3 as per the standard of care. Treatment continues for 1 course in the absence of unacceptable toxicity.
INTENSIVE CONSOLIDATION THERAPY: Patients who go into remission, receive cytarabine IV over 1-3 hours twice daily (BID) on days 1, 3, and 5. Treatment repeats every 4 weeks for 2-4 courses in the absence of disease progression or unacceptable toxicity. Patients treated with liposome-encapsulated daunorubicin-cytarabine receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1 and 3. Treatment repeats every 5-8 weeks for 2 courses in the absence of disease progression, unacceptable toxicity.
Cytarabine: Given IV
Idarubicin: Given IV
Laboratory Biomarker Analysis: Correlative studies
Liposome-encapsulated Daunorubicin-Cytarabine: Given IV
Quality-of-Life Assessment: Ancillary studies
Questionnaire Administration: Ancillary studies
|
Group II
n=65 Participants
LOW-INTENSITY: Patients receive venetoclax in combination with azacitidine or decitabine or other standard of care low-intensity therapy such as azacitidine or decitabine alone or in combination with FLT3 inhibitor such as midostaurin, low-dose cytarabine in combination with glasdegib.
Venetoclax dose varies depending on drug interaction with antifungal agents. Given daily continuous for \>= 3 months orally. Glasdegib dose is 100 mg oral daily.
Decitabine IV over 1-3 hours daily for 5-10 days. Treatment repeats every 4-5 weeks for \>= 3 courses in the absence of disease progression, unacceptable toxicity or receipt of allogeneic stem cell transplant. Azacitidine IV infusion over 10 to 40 minutes days 1 -7. Treatment repeats every 4-5 weeks for \>= 3 courses in the absence of disease progression, unacceptable toxicity or receipt of allogeneic stem cell transplant.
Decitabine: Given IV
Laboratory Biomarker Analysis: Correlative studies
Quality-of-Life Assessment: Ancillary studies
Questionnaire Administration: Ancillary studies
Azacitidine: Given by infusion
Venetoclax: oral tablet
glasdegib: oral tablet
|
Total
n=73 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=15 Participants
|
0 Participants
n=161 Participants
|
0 Participants
n=100 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=15 Participants
|
2 Participants
n=161 Participants
|
2 Participants
n=100 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=15 Participants
|
0 Participants
n=161 Participants
|
0 Participants
n=100 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=15 Participants
|
2 Participants
n=161 Participants
|
2 Participants
n=100 Participants
|
|
Race (NIH/OMB)
White
|
7 Participants
n=15 Participants
|
60 Participants
n=161 Participants
|
67 Participants
n=100 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=15 Participants
|
1 Participants
n=161 Participants
|
2 Participants
n=100 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=15 Participants
|
0 Participants
n=161 Participants
|
0 Participants
n=100 Participants
|
|
Symptom Burden
|
0 units on a scale
n=15 Participants
|
16.7 units on a scale
n=161 Participants
|
16.7 units on a scale
n=100 Participants
|
|
Quality of Life as Measured by EORTC QLQ-C30 Version 3.0 at Baseline
|
75 Units on a scale
n=15 Participants
|
50 Units on a scale
n=161 Participants
|
50 Units on a scale
n=100 Participants
|
|
Baseline Functional Status
|
90 score (0-100 scale)
n=15 Participants
|
80 score (0-100 scale)
n=161 Participants
|
80 score (0-100 scale)
n=100 Participants
|
|
Neurocognitive Status by MoCA at Baseline
|
28 units on a scale
n=15 Participants
|
23 units on a scale
n=161 Participants
|
23 units on a scale
n=100 Participants
|
|
Age, Categorical
<=18 years
|
0 Participants
n=15 Participants
|
0 Participants
n=161 Participants
|
0 Participants
n=100 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
5 Participants
n=15 Participants
|
17 Participants
n=161 Participants
|
22 Participants
n=100 Participants
|
|
Age, Categorical
>=65 years
|
3 Participants
n=15 Participants
|
48 Participants
n=161 Participants
|
51 Participants
n=100 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=15 Participants
|
34 Participants
n=161 Participants
|
36 Participants
n=100 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=15 Participants
|
31 Participants
n=161 Participants
|
37 Participants
n=100 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=15 Participants
|
3 Participants
n=161 Participants
|
4 Participants
n=100 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
7 Participants
n=15 Participants
|
61 Participants
n=161 Participants
|
68 Participants
n=100 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=15 Participants
|
1 Participants
n=161 Participants
|
1 Participants
n=100 Participants
|
|
Baseline Functional Status Measure by Geriatric Assessment
Katz ADL Index
|
6 units on a scale
n=15 Participants
|
6 units on a scale
n=161 Participants
|
6 units on a scale
n=100 Participants
|
|
Baseline Functional Status Measure by Geriatric Assessment
Lawton IADL Index
|
8 units on a scale
n=15 Participants
|
8 units on a scale
n=161 Participants
|
8 units on a scale
n=100 Participants
|
|
Baseline Functional Status Measure by Geriatric Assessment
SPPB
|
11 units on a scale
n=15 Participants
|
7 units on a scale
n=161 Participants
|
7 units on a scale
n=100 Participants
|
PRIMARY outcome
Timeframe: At 90 daysPopulation: "It was pre-specified to report for the entire cohort as a whole in this Outcome Measure. Results for each Arm/Group are pre-specified to be reported separately in Outcome Measure 2,"
All analyses will be performed based on intent-to-treat principle. The method of inversion will be used to generate an interval estimate for the proportion of 90-day mortality.
Outcome measures
| Measure |
Entire Cohort
n=73 Participants
Includes entire study cohort of older adults.
|
Group II
LOW-INTENSITY: Patients receive venetoclax in combination with azacitidine or decitabine or other standard of care low-intensity therapy such as azacitidine or decitabine alone or in combination with FLT3 inhibitor such as midostaurin, low-dose cytarabine in combination with glasdegib.
Venetoclax dose varies depending on drug interaction with antifungal agents. Given daily continuous for \>= 3 months orally. Glasdegib dose is 100 mg oral daily.
Decitabine IV over 1-3 hours daily for 5-10 days. Treatment repeats every 4-5 weeks for \>= 3 courses in the absence of disease progression, unacceptable toxicity or receipt of allogeneic stem cell transplant. Azacitidine IV infusion over 10 to 40 minutes days 1 -7. Treatment repeats every 4-5 weeks for \>= 3 courses in the absence of disease progression, unacceptable toxicity or receipt of allogeneic stem cell transplant.
Decitabine: Given IV
Laboratory Biomarker Analysis: Correlative studies
Quality-of-Life Assessment: Ancillary studies
Questionnaire Administration: Ancillary studies
Azacitidine: Given by infusion
Venetoclax: oral tablet
glasdegib: oral tablet
|
|---|---|---|
|
Rate of Complete Remission and Mortality in the Entire Cohort of Older Patients
90-Day Mortality
|
21.9 percentage of subjects
|
—
|
|
Rate of Complete Remission and Mortality in the Entire Cohort of Older Patients
Remission
|
52.0 percentage of subjects
|
—
|
SECONDARY outcome
Timeframe: At 90 daysAll analyses will be performed based on intent-to-treat principle. The method of inversion will be used to generate an interval estimate for the proportion of 90-day mortality.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: At 90 daysWill assess the impact of baseline functional status on the rate of complete remission and mortality.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to 90 daysWill evaluate the influence of baseline functional status on the quality of life and neurocognitive status. The association between categories of functional status and quality of life will be explored using analysis of variance (ANOVA); if assumptions of ANOVA fail, Kruskal Wallis will be used. The association between functional status (fit or vulnerable) and neurocognitive status (\< 25 or 26 or higher) will be explored using a chi-square test. A generalized linear mixed model will be utilized to evaluate changes in quality of life over time. The proportion (and associated 95% confidence interval) of patients with definitely or probably modifiable impairments will be presented.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline (diagnosis), 10, 30 and 90 days following initiation of chemotherapySymptom burden will be determined using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C-30 (EORTC QLQ-C30) at four time points. This instrument asks 28 questions about symptoms and their effects which are scored 1 to 4. Higher scores indicate worse symptoms and effects. Two additional questions ask about overall health and quality of life during the past week and are scored 1 to 7. Higher scores indicate better weekly health and quality of life.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to 90 days from diagnosisMortality at 90 days will be calculated from date of diagnosis to date of death due to any cause within 90 days from diagnosis.
Outcome measures
| Measure |
Entire Cohort
n=8 Participants
Includes entire study cohort of older adults.
|
Group II
n=65 Participants
LOW-INTENSITY: Patients receive venetoclax in combination with azacitidine or decitabine or other standard of care low-intensity therapy such as azacitidine or decitabine alone or in combination with FLT3 inhibitor such as midostaurin, low-dose cytarabine in combination with glasdegib.
Venetoclax dose varies depending on drug interaction with antifungal agents. Given daily continuous for \>= 3 months orally. Glasdegib dose is 100 mg oral daily.
Decitabine IV over 1-3 hours daily for 5-10 days. Treatment repeats every 4-5 weeks for \>= 3 courses in the absence of disease progression, unacceptable toxicity or receipt of allogeneic stem cell transplant. Azacitidine IV infusion over 10 to 40 minutes days 1 -7. Treatment repeats every 4-5 weeks for \>= 3 courses in the absence of disease progression, unacceptable toxicity or receipt of allogeneic stem cell transplant.
Decitabine: Given IV
Laboratory Biomarker Analysis: Correlative studies
Quality-of-Life Assessment: Ancillary studies
Questionnaire Administration: Ancillary studies
Azacitidine: Given by infusion
Venetoclax: oral tablet
glasdegib: oral tablet
|
|---|---|---|
|
Mortality at 90 Days
|
1 participants
|
15 participants
|
SECONDARY outcome
Timeframe: Several time points after completion of treatment, up to 2 yearsThe European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30), Version 3.0, will be given at several time points in follow-up after completion of treatment. The instrument assesses cancer patients' physical, psychological and social functions. The questionnaire is composed of multi-item scales and single items. A linear transformation is used to standardise the raw score, so that scores range from 0 to 100; a higher score represents a higher ("better") level of functioning, or a higher ("worse") level of symptoms. The scores will be utilized to determine quality of life status will be used to evaluate changes in quality of life over time.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Several time points after completion of treatment, up to 2 yearsThe Montreal Cognitive Assessment (MoCA) will be given at several time points in follow-up after completion of treatment. The instrument assesses different cognitive domains, including attention, visuospatial skills, executive functions, memory, language, and abstract thinking. Each task has a specific scoring guide, with points awarded based on performance. Composite scores of 26-30 generally indicates normal cognitive function, 18-25 suggests mild cognitive impairment, 10-17 indicates moderate impairment, and scores below 10 point to severe cognitive impairment.
Outcome measures
Outcome data not reported
Adverse Events
Group I
Serious events: 5 serious events
Other events: 7 other events
Deaths: 1 deaths
Group II
Serious events: 41 serious events
Other events: 65 other events
Deaths: 15 deaths
Serious adverse events
| Measure |
Group I
n=8 participants at risk
INTENSIVE INDUCTION THERAPY: Patients receive cytarabine intravenously (IV) on days 1-7 and idarubicin over 10-15 minutes on days 1-3 (7+3), or liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1, 3 and 5. Gemtuzumab or midostaurin are added to 7+3 as per the standard of care. Treatment continues for 1 course in the absence of unacceptable toxicity.
INTENSIVE CONSOLIDATION THERAPY: Patients who go into remission, receive cytarabine IV over 1-3 hours twice daily (BID) on days 1, 3, and 5. Treatment repeats every 4 weeks for 2-4 courses in the absence of disease progression or unacceptable toxicity. Patients treated with liposome-encapsulated daunorubicin-cytarabine receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1 and 3. Treatment repeats every 5-8 weeks for 2 courses in the absence of disease progression, unacceptable toxicity.
Cytarabine: Given IV
Idarubicin: Given IV
Laboratory Biomarker Analysis: Correlative studies
Liposome-encapsulated Daunorubicin-Cytarabine: Given IV
Quality-of-Life Assessment: Ancillary studies
Questionnaire Administration: Ancillary studies
|
Group II
n=65 participants at risk
LOW-INTENSITY: Patients receive venetoclax in combination with azacitidine or decitabine or other standard of care low-intensity therapy such as azacitidine or decitabine alone or in combination with FLT3 inhibitor such as midostaurin, low-dose cytarabine in combination with glasdegib.
Venetoclax dose varies depending on drug interaction with antifungal agents. Given daily continuous for \>= 3 months orally. Glasdegib dose is 100 mg oral daily.
Decitabine IV over 1-3 hours daily for 5-10 days. Treatment repeats every 4-5 weeks for \>= 3 courses in the absence of disease progression, unacceptable toxicity or receipt of allogeneic stem cell transplant. Azacitidine IV infusion over 10 to 40 minutes days 1 -7. Treatment repeats every 4-5 weeks for \>= 3 courses in the absence of disease progression, unacceptable toxicity or receipt of allogeneic stem cell transplant.
Decitabine: Given IV
Laboratory Biomarker Analysis: Correlative studies
Quality-of-Life Assessment: Ancillary studies
Questionnaire Administration: Ancillary studies
Azacitidine: Given by infusion
Venetoclax: oral tablet
glasdegib: oral tablet
|
|---|---|---|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
25.0%
2/8 • Number of events 2 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
29.2%
19/65 • Number of events 20 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
|
General disorders
Fever
|
25.0%
2/8 • Number of events 2 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
4.6%
3/65 • Number of events 5 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
|
Gastrointestinal disorders
Gallbladder infection
|
12.5%
1/8 • Number of events 1 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
0.00%
0/65 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
|
Infections and infestations
Catheter-related infection
|
0.00%
0/8 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
3.1%
2/65 • Number of events 2 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
|
Cardiac disorders
Cardiac disorders - Other
|
0.00%
0/8 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
1.5%
1/65 • Number of events 1 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
|
General disorders
Death NOS
|
0.00%
0/8 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
6.2%
4/65 • Number of events 4 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
|
Investigations
Investigations - Other
|
0.00%
0/8 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
1.5%
1/65 • Number of events 1 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
|
Blood and lymphatic system disorders
Neutrophil count decreased
|
0.00%
0/8 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
1.5%
1/65 • Number of events 1 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
|
Infections and infestations
Skin infection
|
0.00%
0/8 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
3.1%
2/65 • Number of events 2 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
|
Infections and infestations
Soft tissue infection
|
0.00%
0/8 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
1.5%
1/65 • Number of events 1 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
0.00%
0/8 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
3.1%
2/65 • Number of events 2 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
|
Metabolism and nutrition disorders
Tumor lysis syndrome
|
0.00%
0/8 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
1.5%
1/65 • Number of events 1 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
|
Nervous system disorders
Depressed level of consciousness
|
0.00%
0/8 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
1.5%
1/65 • Number of events 1 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
|
Nervous system disorders
Syncope
|
0.00%
0/8 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
1.5%
1/65 • Number of events 1 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
|
Renal and urinary disorders
Acute kidney injury
|
0.00%
0/8 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
1.5%
1/65 • Number of events 1 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
|
Renal and urinary disorders
Chronic kidney disease
|
0.00%
0/8 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
1.5%
1/65 • Number of events 1 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
|
Renal and urinary disorders
Renal/Urinary disorders - Other
|
0.00%
0/8 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
1.5%
1/65 • Number of events 1 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
0.00%
0/8 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
3.1%
2/65 • Number of events 2 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/8 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
9.2%
6/65 • Number of events 6 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/8 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
1.5%
1/65 • Number of events 1 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary edema
|
0.00%
0/8 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
1.5%
1/65 • Number of events 1 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.00%
0/8 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
1.5%
1/65 • Number of events 1 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
|
Vascular disorders
Hematoma
|
0.00%
0/8 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
3.1%
2/65 • Number of events 2 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
|
Hepatobiliary disorders
Cholecystitis
|
12.5%
1/8 • Number of events 1 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
1.5%
1/65 • Number of events 1 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
|
Nervous system disorders
Stroke
|
0.00%
0/8 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
3.1%
2/65 • Number of events 3 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
|
Nervous system disorders
Nervous system disorders - Other
|
0.00%
0/8 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
1.5%
1/65 • Number of events 1 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
|
Nervous system disorders
Dizziness
|
0.00%
0/8 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
1.5%
1/65 • Number of events 1 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
|
Gastrointestinal disorders
Enterocolitis
|
0.00%
0/8 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
1.5%
1/65 • Number of events 1 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
|
Gastrointestinal disorders
Gastric hemorrhage
|
0.00%
0/8 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
3.1%
2/65 • Number of events 3 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/8 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
1.5%
1/65 • Number of events 1 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
|
Cardiac disorders
Heart failure
|
0.00%
0/8 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
1.5%
1/65 • Number of events 1 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
|
Cardiac disorders
Supraventricular tachycardia
|
0.00%
0/8 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
1.5%
1/65 • Number of events 1 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/8 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
3.1%
2/65 • Number of events 2 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
Other adverse events
| Measure |
Group I
n=8 participants at risk
INTENSIVE INDUCTION THERAPY: Patients receive cytarabine intravenously (IV) on days 1-7 and idarubicin over 10-15 minutes on days 1-3 (7+3), or liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1, 3 and 5. Gemtuzumab or midostaurin are added to 7+3 as per the standard of care. Treatment continues for 1 course in the absence of unacceptable toxicity.
INTENSIVE CONSOLIDATION THERAPY: Patients who go into remission, receive cytarabine IV over 1-3 hours twice daily (BID) on days 1, 3, and 5. Treatment repeats every 4 weeks for 2-4 courses in the absence of disease progression or unacceptable toxicity. Patients treated with liposome-encapsulated daunorubicin-cytarabine receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1 and 3. Treatment repeats every 5-8 weeks for 2 courses in the absence of disease progression, unacceptable toxicity.
Cytarabine: Given IV
Idarubicin: Given IV
Laboratory Biomarker Analysis: Correlative studies
Liposome-encapsulated Daunorubicin-Cytarabine: Given IV
Quality-of-Life Assessment: Ancillary studies
Questionnaire Administration: Ancillary studies
|
Group II
n=65 participants at risk
LOW-INTENSITY: Patients receive venetoclax in combination with azacitidine or decitabine or other standard of care low-intensity therapy such as azacitidine or decitabine alone or in combination with FLT3 inhibitor such as midostaurin, low-dose cytarabine in combination with glasdegib.
Venetoclax dose varies depending on drug interaction with antifungal agents. Given daily continuous for \>= 3 months orally. Glasdegib dose is 100 mg oral daily.
Decitabine IV over 1-3 hours daily for 5-10 days. Treatment repeats every 4-5 weeks for \>= 3 courses in the absence of disease progression, unacceptable toxicity or receipt of allogeneic stem cell transplant. Azacitidine IV infusion over 10 to 40 minutes days 1 -7. Treatment repeats every 4-5 weeks for \>= 3 courses in the absence of disease progression, unacceptable toxicity or receipt of allogeneic stem cell transplant.
Decitabine: Given IV
Laboratory Biomarker Analysis: Correlative studies
Quality-of-Life Assessment: Ancillary studies
Questionnaire Administration: Ancillary studies
Azacitidine: Given by infusion
Venetoclax: oral tablet
glasdegib: oral tablet
|
|---|---|---|
|
Blood and lymphatic system disorders
Anemia
|
87.5%
7/8 • Number of events 7 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
100.0%
65/65 • Number of events 65 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
87.5%
7/8 • Number of events 7 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
100.0%
65/65 • Number of events 65 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
|
Blood and lymphatic system disorders
Platelet count decreased
|
87.5%
7/8 • Number of events 7 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
100.0%
65/65 • Number of events 65 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
|
Blood and lymphatic system disorders
Neutrophil count decreased
|
87.5%
7/8 • Number of events 7 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
96.9%
63/65 • Number of events 63 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
|
Blood and lymphatic system disorders
White blood cell decreased
|
0.00%
0/8 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
6.2%
4/65 • Number of events 4 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
|
Investigations
Blood bilirubin increased
|
25.0%
2/8 • Number of events 2 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
4.6%
3/65 • Number of events 5 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
|
Metabolism and nutrition disorders
Hyponatremia
|
12.5%
1/8 • Number of events 2 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
4.6%
3/65 • Number of events 5 • Ongoing from initiation of study drug until 30 days after last administration of study drug, up to 20 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place