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Trial record 22 of 324 for:    CYTARABINE AND DAUNORUBICIN

Cytarabine and Daunorubicin Hydrochloride or Idarubicin and Cytarabine With or Without Vorinostat in Treating Younger Patients With Previously Untreated Acute Myeloid Leukemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01802333
Recruitment Status : Completed
First Posted : March 1, 2013
Results First Posted : December 18, 2018
Last Update Posted : December 18, 2018
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions Acute Myeloid Leukemia
Untreated Adult Acute Myeloid Leukemia
Interventions Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
Drug: Cytarabine
Drug: Daunorubicin Hydrochloride
Drug: Idarubicin
Other: Laboratory Biomarker Analysis
Drug: Vorinostat
Enrollment 754
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Arm I (Standard Dose Cytarabine, Daunorubicin Hydrochloride) Arm II (High-dose Cytarabine, Idarubicin) Arm III (Vorinostat, High-dose Cytarabine, Idarubicin)
Hide Arm/Group Description

INDUCTION/RE-INDUCTION: Patients receive standard dose cytarabine IV continuously on days 1-7 and daunorubicin hydrochloride IV on days 1-3. Patients with residual blasts may receive re-induction treatment beginning on day 15. Patients achieving CR or CRi may proceed to allogeneic HSCT or to consolidation therapy.

CONSOLIDATION: Patients receive cytarabine IV over 3 hours every 12 hours on days 1, 3, and 5.

TRANSPLANT: Patients may undergo an allogeneic transplant after induction therapy or consolidation therapy.

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic transplant

Cytarabine: Given IV

Daunorubicin Hydrochloride: Given IV

Laboratory Biomarker Analysis: Correlative studies

INDUCTION/RE-INDUCTION: Patients receive high dose cytarabine IV continuously on days 1-4 and idarubicin IV over 15 minutes on days 1-3. Patients with residual blasts may receive re-induction treatment beginning on day 28. Patients achieving CR or CRi may proceed to allogeneic HSCT or to consolidation therapy.

CONSOLIDATION: Patients receive cytarabine IV continuously on days 1-3 and idarubicin IV over 15 minutes on days 1-2.

TRANSPLANT: Patients may undergo an allogeneic transplant after induction therapy or consolidation therapy.

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic transplant

Cytarabine: Given IV

Idarubicin: Given IV

Laboratory Biomarker Analysis: Correlative studies

INDUCTION/RE-INDUCTION: Patients receive vorinostat PO TID on days 1-3, high-dose cytarabine IV continuously on days 4-7, and idarubicin IV over 15 minutes on days 4-6. Patients with residual blasts may receive re-induction treatment beginning on day 28. Patients achieving CR or CRi may proceed to allogeneic HSCT or to consolidation therapy.

CONSOLIDATION: Patients receive vorinostat PO TID on days 1-3, cytarabine IV continuously on days 4-6, and idarubicin IV over 15 minutes on days 4-5.

TRANSPLANT: Patients may undergo an allogeneic transplant after induction therapy or consolidation therapy. (Permanently closed to accrual, effective 6/2/2015) Patients previously randomized to Arm III may continue treatment with or without vorinostat.

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic transplant

Cytarabine: Given IV

Idarubicin: Given IV

Laboratory Biomarker Analysis: Correlative studies

Vorinostat: Given PO

Period Title: Overall Study
Started 263 267 224
High Risk Patients 60 61 38
High Risk Patients Achieved CR/CRi 38 40 29
Known NPM1 Status at Baseline 169 156 142
Known Cytogenetic Risk at Baseline 252 250 210
Completed 214 206 161
Not Completed 49 61 63
Reason Not Completed
Ineligible             2             6             8
Adverse Event             1             8             8
Withdrawal by Subject             6             6             5
Progression/relapse             1             3             0
Death             7             14             13
Other - not protocol specified             32             22             24
Did not start treatment             0             2             5
Arm/Group Title Arm I (Standard Dose Cytarabine, Daunorubicin Hydrochloride) Arm II (High-dose Cytarabine, Idarubicin) Arm III (Vorinostat, High-dose Cytarabine, Idarubicin) Total
Hide Arm/Group Description

INDUCTION/RE-INDUCTION: Patients receive standard dose cytarabine IV continuously on days 1-7 and daunorubicin hydrochloride IV on days 1-3. Patients with residual blasts may receive re-induction treatment beginning on day 15. Patients achieving CR or CRi may proceed to allogeneic HSCT or to consolidation therapy.

CONSOLIDATION: Patients receive cytarabine IV over 3 hours every 12 hours on days 1, 3, and 5.

TRANSPLANT: Patients may undergo an allogeneic transplant after induction therapy or consolidation therapy.

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic transplant

Cytarabine: Given IV

Daunorubicin Hydrochloride: Given IV

Laboratory Biomarker Analysis: Correlative studies

INDUCTION/RE-INDUCTION: Patients receive high dose cytarabine IV continuously on days 1-4 and idarubicin IV over 15 minutes on days 1-3. Patients with residual blasts may receive re-induction treatment beginning on day 28. Patients achieving CR or CRi may proceed to allogeneic HSCT or to consolidation therapy.

CONSOLIDATION: Patients receive cytarabine IV continuously on days 1-3 and idarubicin IV over 15 minutes on days 1-2.

TRANSPLANT: Patients may undergo an allogeneic transplant after induction therapy or consolidation therapy.

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic transplant

Cytarabine: Given IV

Idarubicin: Given IV

Laboratory Biomarker Analysis: Correlative studies

INDUCTION/RE-INDUCTIONI: Patients receive vorinostat PO TID on days 1-3, high-dose cytarabine IV continuously on days 4-7, and idarubicin IV over 15 minutes on days 4-6. Patients with residual blasts may receive re-induction treatment beginning on day 28. Patients achieving CR or CRi may proceed to allogeneic HSCT or to consolidation therapy.

CONSOLIDATION: Patients receive vorinostat PO TID on days 1-3, cytarabine IV continuously on days 4-6, and idarubicin IV over 15 minutes on days 4-5.

TRANSPLANT: Patients may undergo an allogeneic transplant after induction therapy or consolidation therapy. (Permanently closed to accrual, effective 6/2/2015) Patients previously randomized to Arm III may continue treatment with or without vorinostat.

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic transplant

Cytarabine: Given IV

Idarubicin: Given IV

Laboratory Biomarker Analysis: Correlative studies

Vorinostat: Given PO

Total of all reporting groups
Overall Number of Baseline Participants 261 261 216 738
Hide Baseline Analysis Population Description
Eligible patients
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 261 participants 261 participants 216 participants 738 participants
48.3
(19.2 to 60.8)
51.5
(18.8 to 60.9)
48.9
(19.6 to 61.0)
49.8
(18.8 to 61.0)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 261 participants 261 participants 216 participants 738 participants
< 40 years
68
  26.1%
65
  24.9%
55
  25.5%
188
  25.5%
>= 40 years
193
  73.9%
196
  75.1%
161
  74.5%
550
  74.5%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 261 participants 261 participants 216 participants 738 participants
Female
131
  50.2%
127
  48.7%
102
  47.2%
360
  48.8%
Male
130
  49.8%
134
  51.3%
114
  52.8%
378
  51.2%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 261 participants 261 participants 216 participants 738 participants
Hispanic or Latino
19
   7.3%
22
   8.4%
21
   9.7%
62
   8.4%
Not Hispanic or Latino
226
  86.6%
217
  83.1%
185
  85.6%
628
  85.1%
Unknown or Not Reported
16
   6.1%
22
   8.4%
10
   4.6%
48
   6.5%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 261 participants 261 participants 216 participants 738 participants
American Indian or Alaska Native
3
   1.1%
0
   0.0%
3
   1.4%
6
   0.8%
Asian
6
   2.3%
4
   1.5%
7
   3.2%
17
   2.3%
Native Hawaiian or Other Pacific Islander
2
   0.8%
1
   0.4%
0
   0.0%
3
   0.4%
Black or African American
19
   7.3%
19
   7.3%
17
   7.9%
55
   7.5%
White
218
  83.5%
217
  83.1%
178
  82.4%
613
  83.1%
More than one race
1
   0.4%
1
   0.4%
0
   0.0%
2
   0.3%
Unknown or Not Reported
12
   4.6%
19
   7.3%
11
   5.1%
42
   5.7%
Onset of Leukemia  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 261 participants 261 participants 216 participants 738 participants
De novo
236
  90.4%
236
  90.4%
193
  89.4%
665
  90.1%
Tx. related/arose from antecededent hem. disease
25
   9.6%
25
   9.6%
23
  10.6%
73
   9.9%
1.Primary Outcome
Title Event-free Survival (EFS)
Hide Description

EFS is calculated for all patients from the date of initial registration on study until the first of the following: death from any cause, relapse from remission (CR or CRi) or completion of protocol Induction/Re-Induction therapy without documentation of CR or CRi.

2-year EFS by arm will be estimated using the Kaplan-Meier method. EFS will be compared between Arm I and Arm III and between Arm II and Arm III using Cox proportional hazards regression.

Time Frame EFS assessed for up to 5 years, 2 year EFS reported
Hide Outcome Measure Data
Hide Analysis Population Description
Eligible patients
Arm/Group Title Arm I (Standard Dose Cytarabine, Daunorubicin Hydrochloride) Arm II (High-dose Cytarabine, Idarubicin) Arm III (Vorinostat, High-dose Cytarabine, Idarubicin)
Hide Arm/Group Description:

INDUCTION/RE-INDUCTION: Patients receive standard dose cytarabine IV continuously on days 1-7 and daunorubicin hydrochloride IV on days 1-3. Patients with residual blasts may receive re-induction treatment beginning on day 15. Patients achieving CR or CRi may proceed to allogeneic HSCT or to consolidation therapy.

CONSOLIDATION: Patients receive cytarabine IV over 3 hours every 12 hours on days 1, 3, and 5.

TRANSPLANT: Patients may undergo an allogeneic transplant after induction therapy or consolidation therapy.

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic transplant

Cytarabine: Given IV

Daunorubicin Hydrochloride: Given IV

Laboratory Biomarker Analysis: Correlative studies

INDUCTION/RE-INDUCTION: Patients receive high dose cytarabine IV continuously on days 1-4 and idarubicin IV over 15 minutes on days 1-3. Patients with residual blasts may receive re-induction treatment beginning on day 28. Patients achieving CR or CRi may proceed to allogeneic HSCT or to consolidation therapy.

CONSOLIDATION: Patients receive cytarabine IV continuously on days 1-3 and idarubicin IV over 15 minutes on days 1-2.

TRANSPLANT: Patients may undergo an allogeneic transplant after induction therapy or consolidation therapy.

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic transplant

Cytarabine: Given IV

Idarubicin: Given IV

Laboratory Biomarker Analysis: Correlative studies

INDUCTION/RE-INDUCTIONI: Patients receive vorinostat PO TID on days 1-3, high-dose cytarabine IV continuously on days 4-7, and idarubicin IV over 15 minutes on days 4-6. Patients with residual blasts may receive re-induction treatment beginning on day 28. Patients achieving CR or CRi may proceed to allogeneic HSCT or to consolidation therapy.

CONSOLIDATION: Patients receive vorinostat PO TID on days 1-3, cytarabine IV continuously on days 4-6, and idarubicin IV over 15 minutes on days 4-5.

TRANSPLANT: Patients may undergo an allogeneic transplant after induction therapy or consolidation therapy. (Permanently closed to accrual, effective 6/2/2015) Patients previously randomized to Arm III may continue treatment with or without vorinostat.

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic transplant

Cytarabine: Given IV

Idarubicin: Given IV

Laboratory Biomarker Analysis: Correlative studies

Vorinostat: Given PO

Overall Number of Participants Analyzed 261 261 216
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Proportion of participants
0.36
(0.30 to 0.42)
0.41
(0.35 to 0.46)
0.37
(0.30 to 0.43)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm I (Standard Dose Cytarabine, Daunorubicin Hydrochloride), Arm III (Vorinostat, High-dose Cytarabine, Idarubicin)
Comments Arm I was compared with Arm III using a two-sided test of the null hypothesis (HR=1) at the 0.045 level.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.84
Comments [Not Specified]
Method Regression, Cox
Comments Adjusted for: Age (< 40 vs. >= 40) and Onset of AML (de novo vs. treatment related and/or AML arising from antecedent hematologic disease)
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Arm II (High-dose Cytarabine, Idarubicin), Arm III (Vorinostat, High-dose Cytarabine, Idarubicin)
Comments Arm II was compared with Arm III using a two-sided test of the null hypothesis (HR=1) at the 0.045 level.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.42
Comments [Not Specified]
Method Regression, Cox
Comments Adjusted for: Age (< 40 vs. >= 40) and Onset of AML (de novo vs. treatment related and/or AML arising from antecedent hematologic disease)
2.Primary Outcome
Title Rate of Allogeneic HCT
Hide Description The goal of the transplant objective is to determine whether it is possible to conduct allogeneic HCT on 60% or more of adults with high-risk AML in first complete remission (alternative). If 40% or fewer of high-risk patients in CR can be transplanted, the proposed transplant support system will not be considered feasible. A one-sided binomial test compared to the null transplant rate will be conducted.
Time Frame Up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Eligible patients with high-risk AML who achieved CR or CRi, regardless of treatment arm.
Arm/Group Title High Risk Patients in First Complete Remission
Hide Arm/Group Description:
This group includes patients from any of the three treatment arms who have high-risk AML (by cytogenetics) and who achieved a complete remission (CR) or complete remission with incomplete blood count recovery (CRi).
Overall Number of Participants Analyzed 107
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of patients
65
(56 to 74)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection High Risk Patients in First Complete Remission
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Exact binomial test, 1-sided
Comments [Not Specified]
3.Secondary Outcome
Title Disease-free Survival (DFS) Among High Risk Patients
Hide Description

DFS is calculated for patients who have achieved a CR or CRi (complete response with incomplete blood count recovery). DFS will be measured from the date of CR or CRi until relapse from CR or CRi for death from any cause. Observation is censored at the date of last follow-up for patients last known to be alive without report of relapse.

2-year DFS for high risk patients will be estimated using the Kaplan-Meier method.

Time Frame DFS assessed for up to 5 years, 2 year DFS reported
Hide Outcome Measure Data
Hide Analysis Population Description
Eligible, high risk patients, regardless of treatment arm.
Arm/Group Title High Risk Patients
Hide Arm/Group Description:
This group includes patients from any of the three treatment arms who have high-risk AML (by cytogenetics).
Overall Number of Participants Analyzed 159
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Proportion of participants
0.30
(0.21 to 0.39)
4.Secondary Outcome
Title EFS of Arm I Compared to Arm II
Hide Description

EFS is calculated for all patients from the date of initial registration on study until the first of the following: death from any cause, relapse from remission (CR or CRi) or completion of protocol Induction/Re-Induction therapy without documentation of CR or CRi.

A two-sided test of the hazard ratio (HR) of 7:3: IA (versus the null hypothesis of HR =1) will be done using a proportional hazards regression model with the stratification factors included as covariates.

2-year EFS by arm will be estimated using the Kaplan-Meier method.

Time Frame EFS assessed for up to 5 years, 2 year EFS reported
Hide Outcome Measure Data
Hide Analysis Population Description
Eligible patients
Arm/Group Title Arm I (Standard Dose Cytarabine, Daunorubicin Hydrochloride) Arm II (High-dose Cytarabine, Idarubicin)
Hide Arm/Group Description:

INDUCTION/RE-INDUCTION: Patients receive standard dose cytarabine IV continuously on days 1-7 and daunorubicin hydrochloride IV on days 1-3. Patients with residual blasts may receive re-induction treatment beginning on day 15. Patients achieving CR or CRi may proceed to allogeneic HSCT or to consolidation therapy.

CONSOLIDATION: Patients receive cytarabine IV over 3 hours every 12 hours on days 1, 3, and 5.

TRANSPLANT: Patients may undergo an allogeneic transplant after induction therapy or consolidation therapy.

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic transplant

Cytarabine: Given IV

Daunorubicin Hydrochloride: Given IV

Laboratory Biomarker Analysis: Correlative studies

INDUCTION/RE-INDUCTION: Patients receive high dose cytarabine IV continuously on days 1-4 and idarubicin IV over 15 minutes on days 1-3. Patients with residual blasts may receive re-induction treatment beginning on day 28. Patients achieving CR or CRi may proceed to allogeneic HSCT or to consolidation therapy.

CONSOLIDATION: Patients receive cytarabine IV continuously on days 1-3 and idarubicin IV over 15 minutes on days 1-2.

TRANSPLANT: Patients may undergo an allogeneic transplant after induction therapy or consolidation therapy.

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic transplant

Cytarabine: Given IV

Idarubicin: Given IV

Laboratory Biomarker Analysis: Correlative studies

Overall Number of Participants Analyzed 261 261
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Proportion of participants
0.36
(0.30 to 0.42)
0.41
(0.35 to 0.46)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm I (Standard Dose Cytarabine, Daunorubicin Hydrochloride), Arm II (High-dose Cytarabine, Idarubicin)
Comments Arm I was compared with Arm II using a two-sided test of the null hypothesis (HR=1).
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.52
Comments [Not Specified]
Method Regression, Cox
Comments Adjusted for: Age (< 40 vs. >= 40) and Onset of AML (de novo vs. treatment related and/or AML arising from antecedent hematologic disease)
5.Secondary Outcome
Title Frequency and Severity of Toxicities
Hide Description Number of patients with Grade 3-5 adverse events that were possibly, probably or definitely related to study drug are reported by given type of adverse event.
Time Frame Up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Eligible patients who started treatment
Arm/Group Title Arm I (Standard Dose Cytarabine, Daunorubicin Hydrochloride) Arm II (High-dose Cytarabine, Idarubicin) Arm III (Vorinostat, High-dose Cytarabine, Idarubicin)
Hide Arm/Group Description:
INDUCTION/RE-INDUCTION: Patients receive standard dose cytarabine IV continuously on days 1-7 and daunorubicin hydrochloride IV on days 1-3. Patients with residual blasts may receive re-induction treatment beginning on day 15. Patients achieving CR or CRi may proceed to allogeneic HSCT or to consolidation therapy.
INDUCTION/RE-INDUCTION: Patients receive high dose cytarabine IV continuously on days 1-4 and idarubicin IV over 15 minutes on days 1-3. Patients with residual blasts may receive re-induction treatment beginning on day 28. Patients achieving CR or CRi may proceed to allogeneic HSCT or to consolidation therapy.
INDUCTION/RE-INDUCTION: Patients receive vorinostat PO TID on days 1-3, high-dose cytarabine IV continuously on days 4-7, and idarubicin IV over 15 minutes on days 4-6. Patients with residual blasts may receive re-induction treatment beginning on day 28. Patients achieving CR or CRi may proceed to allogeneic HSCT or to consolidation therapy.
Overall Number of Participants Analyzed 261 259 211
Measure Type: Count of Participants
Unit of Measure: Participants
Abdominal distension 1 0 1
Abdominal infection 1 1 1
Abdominal pain 4 6 9
Acidosis 1 1 2
Acute kidney injury 2 5 4
Adult respiratory distress syndrome 1 3 4
Alanine aminotransferase increased 12 17 20
Alkaline phosphatase increased 2 2 1
Alkalosis 1 1 2
Allergic reaction 0 0 2
Anal hemorrhage 0 0 1
Anal pain 0 1 0
Anal ulcer 0 0 1
Anemia 158 164 106
Anorectal infection 0 0 4
Anorexia 5 16 12
Aspartate aminotransferase increased 8 15 12
Atelectasis 0 0 1
Atrial fibrillation 0 3 1
Atrial flutter 0 1 1
Atrioventricular block complete 0 1 0
Blood and lymphatic system disorders - Other 1 1 0
Blood bilirubin increased 9 15 22
Bone infection 1 0 0
Bone pain 0 1 0
Bronchopulmonary hemorrhage 1 1 3
Bullous dermatitis 0 2 0
CD4 lymphocytes decreased 1 1 0
Cardiac arrest 1 3 2
Cardiac disorders - Other, specify 1 1 1
Cardiac troponin I increased 0 1 0
Catheter related infection 3 7 4
Chills 1 0 0
Chronic kidney disease 0 2 0
Cognitive disturbance 0 0 1
Colitis 3 9 5
Colonic hemorrhage 2 0 1
Colonic perforation 0 0 1
Conduction disorder 1 0 0
Confusion 0 2 0
Conjunctivitis 1 0 0
Constipation 0 1 0
Constrictive pericarditis 1 0 0
Creatinine increased 1 6 4
Death NOS 1 1 0
Dehydration 1 0 3
Dental caries 1 0 0
Device related infection 1 3 0
Diarrhea 15 20 38
Disseminated intravascular coagulation 2 1 1
Dry mouth 0 1 0
Dry skin 0 2 0
Duodenal hemorrhage 1 0 0
Dyspepsia 1 0 0
Dysphagia 1 1 0
Dyspnea 3 7 8
Edema cerebral 0 0 1
Edema limbs 0 3 2
Ejection fraction decreased 2 6 4
Electrocardiogram QT corrected interval prolonged 0 2 2
Encephalopathy 0 1 0
Enterocolitis 1 6 5
Enterocolitis infectious 1 4 4
Epistaxis 2 1 2
Erythema multiforme 1 0 0
Erythroderma 0 0 1
Esophageal hemorrhage 0 0 1
Esophageal pain 1 1 0
Esophagitis 3 2 1
Eye infection 0 1 0
Fatigue 14 18 13
Febrile neutropenia 152 160 114
Fever 4 7 6
GGT increased 3 2 4
Gait disturbance 0 0 1
Gastric hemorrhage 0 2 3
Gastritis 1 0 0
Gastroesophageal reflux disease 1 0 0
Gastrointestinal disorders - Other, specify 1 5 1
General disorders and admin site conditions-Other 0 4 1
Generalized muscle weakness 2 1 2
Genital edema 0 0 1
Glucose intolerance 1 0 0
Gum infection 1 0 0
Headache 2 2 4
Heart failure 3 2 3
Hematoma 0 1 0
Hematuria 0 2 0
Hepatic failure 1 0 0
Hepatic infection 1 1 0
Hepatobiliary disorders - Other, specify 1 0 1
Hyperglycemia 5 12 16
Hyperhidrosis 1 1 0
Hyperkalemia 0 1 1
Hypermagnesemia 0 1 0
Hypernatremia 0 0 2
Hypertension 7 6 6
Hyperuricemia 0 1 1
Hypoalbuminemia 5 8 8
Hypocalcemia 8 17 25
Hypoglycemia 0 0 1
Hypokalemia 18 20 24
Hypomagnesemia 0 1 2
Hyponatremia 20 20 9
Hypophosphatemia 21 31 31
Hypotension 3 12 9
Hypoxia 2 4 9
Ileus 0 1 2
Infections and infestations - Other, specify 18 21 14
Infective myositis 1 0 0
Injury, poison and procedural complications-Other 1 0 0
Intracranial hemorrhage 0 0 1
Investigations - Other, specify 1 6 3
Irregular menstruation 1 0 0
Jejunal obstruction 0 0 1
Kidney infection 0 1 0
Laryngeal edema 1 0 0
Laryngeal mucositis 0 0 1
Left ventricular systolic dysfunction 2 3 0
Leukocytosis 1 1 1
Lipase increased 0 0 2
Lower gastrointestinal hemorrhage 0 1 3
Lung infection 21 22 14
Lymphocyte count decreased 89 107 77
Menorrhagia 1 0 0
Metabolism and nutrition disorders-Other, specify 1 1 0
Middle ear inflammation 1 0 0
Mucosal infection 1 0 1
Mucositis oral 19 18 11
Multi-organ failure 1 3 5
Musculoskeletal and connective tiss disorder-Other 0 1 1
Myalgia 0 0 1
Nausea 7 15 5
Neck edema 0 0 1
Nervous system disorders - Other, specify 0 1 0
Neutrophil count decreased 141 128 104
Non-cardiac chest pain 1 0 1
Oral pain 5 5 0
Pain 1 0 0
Pain in extremity 1 0 1
Palmar-plantar erythrodysesthesia syndrome 0 2 1
Papulopustular rash 0 1 0
Paresthesia 0 0 1
Pericardial effusion 0 0 1
Pericardial tamponade 0 0 1
Periorbital edema 0 1 0
Peripheral sensory neuropathy 0 0 1
Pharyngeal mucositis 1 0 0
Pharyngitis 1 0 0
Platelet count decreased 175 168 128
Pleural effusion 1 0 1
Pneumonitis 1 4 2
Pruritus 0 1 1
Pulmonary edema 1 2 5
Purpura 0 1 0
Rash acneiform 1 1 0
Rash maculo-papular 11 26 10
Rectal hemorrhage 1 0 0
Rectal pain 1 0 1
Renal and urinary disorders - Other, specify 0 1 0
Resp, thoracic and mediastinal disorders - Other 1 3 2
Respiratory failure 3 8 14
Restrictive cardiomyopathy 1 0 0
Salivary duct inflammation 1 0 0
Scrotal infection 0 0 1
Scrotal pain 0 0 1
Seizure 1 0 1
Sepsis 16 26 34
Sinus bradycardia 0 0 1
Sinus tachycardia 0 2 2
Sinusitis 2 0 0
Skin and subcutaneous tissue disorders - Other 0 2 1
Skin infection 5 1 4
Skin ulceration 0 0 1
Small intestinal obstruction 1 0 0
Soft tissue infection 1 0 0
Sore throat 1 2 2
Stomach pain 1 0 0
Stroke 0 1 1
Supraventricular tachycardia 0 1 1
Syncope 2 2 3
Testicular disorder 0 1 0
Thromboembolic event 1 0 0
Thrombotic thrombocytopenic purpura 3 0 1
Tooth infection 1 0 0
Tumor lysis syndrome 4 8 9
Typhlitis 8 14 23
Upper gastrointestinal hemorrhage 1 0 1
Upper respiratory infection 2 1 2
Urinary incontinence 0 0 1
Urinary tract infection 5 2 6
Urine output decreased 0 0 1
Vaginal hemorrhage 0 0 2
Vascular access complication 0 2 1
Vasovagal reaction 0 1 1
Ventricular tachycardia 0 1 0
Vomiting 3 6 4
Weight loss 2 0 2
White blood cell decreased 156 150 112
Wound infection 1 0 0
6.Other Pre-specified Outcome
Title Prevalence of the Mutation NPM1 in Patients on This Study.
Hide Description To estimate the prevalence of the mutation NPM1 in this patient population.
Time Frame Baseline
Hide Outcome Measure Data
Hide Analysis Population Description
Eligible patients with known NPM1 status at baseline
Arm/Group Title All Arms Combined
Hide Arm/Group Description:
This group includes all patients enrolled to the trial, regardless of treatment assignment.
Overall Number of Participants Analyzed 467
Measure Type: Number
Unit of Measure: percentage of patients
33
7.Other Pre-specified Outcome
Title Prevalence of the Mutations IDH1, IDH2, TET2, DMT3A in Patients on This Study
Hide Description

To estimate the prevalence of these mutations in this patient population.

This objective will be analyzed as funding allows.

Time Frame Baseline
Hide Outcome Measure Data
Hide Analysis Population Description
There was not sufficient funding to test patients for IDH1, IDH2, TET2, or DMT3A. Therefore, this objective was not completed.
Arm/Group Title All Arms Combined
Hide Arm/Group Description:
This group includes all patients enrolled to the trial, regardless of treatment assignment.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
8.Other Pre-specified Outcome
Title Cytogenetic Risk Distribution of Patients on This Study
Hide Description To estimate the cytogenetic risk distribution of patients on this study.
Time Frame Baseline
Hide Outcome Measure Data
Hide Analysis Population Description
Eligible patients with known cytogenetic risk at baseline
Arm/Group Title All Arms Combined
Hide Arm/Group Description:
This group includes all patients enrolled to the trial, regardless of treatment assignment.
Overall Number of Participants Analyzed 712
Measure Type: Number
Unit of Measure: percentage of participants
High risk 22.3
Intermediate risk 64.2
Low risk 13.5
9.Other Pre-specified Outcome
Title Overall Survival (OS)
Hide Description

To compare OS between patients who receive standard 7+3 therapy or IA to patients who receive IA + vorinostat.

OS is calculated for all patients from date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact.

2-year OS by arm will be estimated using the Kaplan-Meier method.

Time Frame OS assessed for up to 5 years, 2 year OS reported
Hide Outcome Measure Data
Hide Analysis Population Description
Eligible patients
Arm/Group Title Arm I (Standard Dose Cytarabine, Daunorubicin Hydrochloride) Arm II (High-dose Cytarabine, Idarubicin) Arm III (Vorinostat, High-dose Cytarabine, Idarubicin)
Hide Arm/Group Description:

INDUCTION/RE-INDUCTION: Patients receive standard dose cytarabine IV continuously on days 1-7 and daunorubicin hydrochloride IV on days 1-3. Patients with residual blasts may receive re-induction treatment beginning on day 15. Patients achieving CR or CRi may proceed to allogeneic HSCT or to consolidation therapy.

CONSOLIDATION: Patients receive cytarabine IV over 3 hours every 12 hours on days 1, 3, and 5.

TRANSPLANT: Patients may undergo an allogeneic transplant after induction therapy or consolidation therapy.

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic transplant

Cytarabine: Given IV

Daunorubicin Hydrochloride: Given IV

Laboratory Biomarker Analysis: Correlative studies

INDUCTION/RE-INDUCTION: Patients receive high dose cytarabine IV continuously on days 1-4 and idarubicin IV over 15 minutes on days 1-3. Patients with residual blasts may receive re-induction treatment beginning on day 28. Patients achieving CR or CRi may proceed to allogeneic HSCT or to consolidation therapy.

CONSOLIDATION: Patients receive cytarabine IV continuously on days 1-3 and idarubicin IV over 15 minutes on days 1-2.

TRANSPLANT: Patients may undergo an allogeneic transplant after induction therapy or consolidation therapy.

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic transplant

Cytarabine: Given IV

Idarubicin: Given IV

Laboratory Biomarker Analysis: Correlative studies

INDUCTION/RE-INDUCTIONI: Patients receive vorinostat PO TID on days 1-3, high-dose cytarabine IV continuously on days 4-7, and idarubicin IV over 15 minutes on days 4-6. Patients with residual blasts may receive re-induction treatment beginning on day 28. Patients achieving CR or CRi may proceed to allogeneic HSCT or to consolidation therapy.

CONSOLIDATION: Patients receive vorinostat PO TID on days 1-3, cytarabine IV continuously on days 4-6, and idarubicin IV over 15 minutes on days 4-5.

TRANSPLANT: Patients may undergo an allogeneic transplant after induction therapy or consolidation therapy. (Permanently closed to accrual, effective 6/2/2015) Patients previously randomized to Arm III may continue treatment with or without vorinostat.

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic transplant

Cytarabine: Given IV

Idarubicin: Given IV

Laboratory Biomarker Analysis: Correlative studies

Vorinostat: Given PO

Overall Number of Participants Analyzed 261 261 216
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Proportion of participants
0.56
(0.50 to 0.62)
0.59
(0.53 to 0.65)
0.58
(0.50 to 0.64)
10.Other Pre-specified Outcome
Title Complete Response (CR) Rate
Hide Description

To compare the complete response rate between patients who receive standard 7+3 therapy or IA to patients who receive IA + vorinostat.

Complete response is defined as: ANC >= 1,000/mcl, platelet count >= 100,000/mcl, < 5% bone marrow blasts, no Auer rods, no evidence of extramedullary disease (no requirements for marrow cellularity or hemoglobin concentration)

Time Frame Up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Eligible patients
Arm/Group Title Arm I (Standard Dose Cytarabine, Daunorubicin Hydrochloride) Arm II (High-dose Cytarabine, Idarubicin) Arm III (Vorinostat, High-dose Cytarabine, Idarubicin)
Hide Arm/Group Description:

INDUCTION/RE-INDUCTION: Patients receive standard dose cytarabine IV continuously on days 1-7 and daunorubicin hydrochloride IV on days 1-3. Patients with residual blasts may receive re-induction treatment beginning on day 15. Patients achieving CR or CRi may proceed to allogeneic HSCT or to consolidation therapy.

CONSOLIDATION: Patients receive cytarabine IV over 3 hours every 12 hours on days 1, 3, and 5.

TRANSPLANT: Patients may undergo an allogeneic transplant after induction therapy or consolidation therapy.

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic transplant

Cytarabine: Given IV

Daunorubicin Hydrochloride: Given IV

Laboratory Biomarker Analysis: Correlative studies

INDUCTION/RE-INDUCTION: Patients receive high dose cytarabine IV continuously on days 1-4 and idarubicin IV over 15 minutes on days 1-3. Patients with residual blasts may receive re-induction treatment beginning on day 28. Patients achieving CR or CRi may proceed to allogeneic HSCT or to consolidation therapy.

CONSOLIDATION: Patients receive cytarabine IV continuously on days 1-3 and idarubicin IV over 15 minutes on days 1-2.

TRANSPLANT: Patients may undergo an allogeneic transplant after induction therapy or consolidation therapy.

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic transplant

Cytarabine: Given IV

Idarubicin: Given IV

Laboratory Biomarker Analysis: Correlative studies

INDUCTION/RE-INDUCTIONI: Patients receive vorinostat PO TID on days 1-3, high-dose cytarabine IV continuously on days 4-7, and idarubicin IV over 15 minutes on days 4-6. Patients with residual blasts may receive re-induction treatment beginning on day 28. Patients achieving CR or CRi may proceed to allogeneic HSCT or to consolidation therapy.

CONSOLIDATION: Patients receive vorinostat PO TID on days 1-3, cytarabine IV continuously on days 4-6, and idarubicin IV over 15 minutes on days 4-5.

TRANSPLANT: Patients may undergo an allogeneic transplant after induction therapy or consolidation therapy. (Permanently closed to accrual, effective 6/2/2015) Patients previously randomized to Arm III may continue treatment with or without vorinostat.

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic transplant

Cytarabine: Given IV

Idarubicin: Given IV

Laboratory Biomarker Analysis: Correlative studies

Vorinostat: Given PO

Overall Number of Participants Analyzed 261 261 216
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
75
(70 to 81)
80
(74 to 84)
77
(71 to 83)
11.Other Pre-specified Outcome
Title Disease-free Survival (DFS)
Hide Description

To compare the disease-free survival (DFS) between patients who receive standard 7+3 therapy or IA to patients who receive IA + vorinostat.

DFS is calculated for patients who have achieved a CR or CRi (complete response with incomplete blood count recovery) . DFS will be measured from the date of CR or CRi until relapse from CR or CRi for death from any cause. Observation is censored at the date of last follow-up for patients last known to be alive without report of relapse.

2-year DFS by arm will be estimated using the Kaplan-Meier method.

Time Frame DFS assessed for up to 5 years, 2 year DFS reported
Hide Outcome Measure Data
Hide Analysis Population Description
Eligible patients
Arm/Group Title Arm I (Standard Dose Cytarabine, Daunorubicin Hydrochloride) Arm II (High-dose Cytarabine, Idarubicin) Arm III (Vorinostat, High-dose Cytarabine, Idarubicin)
Hide Arm/Group Description:

INDUCTION/RE-INDUCTION: Patients receive standard dose cytarabine IV continuously on days 1-7 and daunorubicin hydrochloride IV on days 1-3. Patients with residual blasts may receive re-induction treatment beginning on day 15. Patients achieving CR or CRi may proceed to allogeneic HSCT or to consolidation therapy.

CONSOLIDATION: Patients receive cytarabine IV over 3 hours every 12 hours on days 1, 3, and 5.

TRANSPLANT: Patients may undergo an allogeneic transplant after induction therapy or consolidation therapy.

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic transplant

Cytarabine: Given IV

Daunorubicin Hydrochloride: Given IV

Laboratory Biomarker Analysis: Correlative studies

INDUCTION/RE-INDUCTION: Patients receive high dose cytarabine IV continuously on days 1-4 and idarubicin IV over 15 minutes on days 1-3. Patients with residual blasts may receive re-induction treatment beginning on day 28. Patients achieving CR or CRi may proceed to allogeneic HSCT or to consolidation therapy.

CONSOLIDATION: Patients receive cytarabine IV continuously on days 1-3 and idarubicin IV over 15 minutes on days 1-2.

TRANSPLANT: Patients may undergo an allogeneic transplant after induction therapy or consolidation therapy.

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic transplant

Cytarabine: Given IV

Idarubicin: Given IV

Laboratory Biomarker Analysis: Correlative studies

INDUCTION/RE-INDUCTIONI: Patients receive vorinostat PO TID on days 1-3, high-dose cytarabine IV continuously on days 4-7, and idarubicin IV over 15 minutes on days 4-6. Patients with residual blasts may receive re-induction treatment beginning on day 28. Patients achieving CR or CRi may proceed to allogeneic HSCT or to consolidation therapy.

CONSOLIDATION: Patients receive vorinostat PO TID on days 1-3, cytarabine IV continuously on days 4-6, and idarubicin IV over 15 minutes on days 4-5.

TRANSPLANT: Patients may undergo an allogeneic transplant after induction therapy or consolidation therapy. (Permanently closed to accrual, effective 6/2/2015) Patients previously randomized to Arm III may continue treatment with or without vorinostat.

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic transplant

Cytarabine: Given IV

Idarubicin: Given IV

Laboratory Biomarker Analysis: Correlative studies

Vorinostat: Given PO

Overall Number of Participants Analyzed 261 261 216
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Proportion of participants
0.48
(0.41 to 0.55)
0.51
(0.44 to 0.57)
0.46
(0.38 to 0.54)
Time Frame Up to 5 years
Adverse Event Reporting Description Number of patients with adverse events are reported by type of adverse event. All adverse events, regardless of attribution or grade, are reported. Adverse events are reported for eligible patients who started treatment.
 
Arm/Group Title Arm I (Standard Dose Cytarabine, Daunorubicin Hydrochloride) Arm II (High-dose Cytarabine, Idarubicin) Arm III (Vorinostat, High-dose Cytarabine, Idarubicin)
Hide Arm/Group Description INDUCTION/RE-INDUCTION: Patients receive standard dose cytarabine IV continuously on days 1-7 and daunorubicin hydrochloride IV on days 1-3. Patients with residual blasts may receive re-induction treatment beginning on day 15. Patients achieving CR or CRi may proceed to allogeneic HSCT or to consolidation therapy. INDUCTION/RE-INDUCTION: Patients receive high dose cytarabine IV continuously on days 1-4 and idarubicin IV over 15 minutes on days 1-3. Patients with residual blasts may receive re-induction treatment beginning on day 28. Patients achieving CR or CRi may proceed to allogeneic HSCT or to consolidation therapy. INDUCTION/RE-INDUCTION: Patients receive vorinostat PO TID on days 1-3, high-dose cytarabine IV continuously on days 4-7, and idarubicin IV over 15 minutes on days 4-6. Patients with residual blasts may receive re-induction treatment beginning on day 28. Patients achieving CR or CRi may proceed to allogeneic HSCT or to consolidation therapy.
All-Cause Mortality
Arm I (Standard Dose Cytarabine, Daunorubicin Hydrochloride) Arm II (High-dose Cytarabine, Idarubicin) Arm III (Vorinostat, High-dose Cytarabine, Idarubicin)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   126/261 (48.28%)   114/259 (44.02%)   103/211 (48.82%) 
Show Serious Adverse Events Hide Serious Adverse Events
Arm I (Standard Dose Cytarabine, Daunorubicin Hydrochloride) Arm II (High-dose Cytarabine, Idarubicin) Arm III (Vorinostat, High-dose Cytarabine, Idarubicin)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   11/261 (4.21%)   27/259 (10.42%)   75/211 (35.55%) 
Blood and lymphatic system disorders       
Febrile neutropenia   1/261 (0.38%)  4/259 (1.54%)  13/211 (6.16%) 
Leukocytosis   0/261 (0.00%)  0/259 (0.00%)  1/211 (0.47%) 
Cardiac disorders       
Atrial fibrillation   0/261 (0.00%)  2/259 (0.77%)  1/211 (0.47%) 
Atrial flutter   0/261 (0.00%)  0/259 (0.00%)  1/211 (0.47%) 
Cardiac arrest   1/261 (0.38%)  4/259 (1.54%)  2/211 (0.95%) 
Heart failure   0/261 (0.00%)  0/259 (0.00%)  1/211 (0.47%) 
Pericardial effusion   0/261 (0.00%)  0/259 (0.00%)  3/211 (1.42%) 
Pericardial tamponade   0/261 (0.00%)  0/259 (0.00%)  1/211 (0.47%) 
Sinus tachycardia   0/261 (0.00%)  1/259 (0.39%)  3/211 (1.42%) 
Supraventricular tachycardia   0/261 (0.00%)  0/259 (0.00%)  1/211 (0.47%) 
Gastrointestinal disorders       
Abdominal distension   0/261 (0.00%)  0/259 (0.00%)  1/211 (0.47%) 
Abdominal pain   0/261 (0.00%)  0/259 (0.00%)  5/211 (2.37%) 
Colitis   0/261 (0.00%)  0/259 (0.00%)  6/211 (2.84%) 
Colonic hemorrhage   0/261 (0.00%)  0/259 (0.00%)  1/211 (0.47%) 
Colonic perforation   0/261 (0.00%)  0/259 (0.00%)  1/211 (0.47%) 
Diarrhea   0/261 (0.00%)  0/259 (0.00%)  6/211 (2.84%) 
Enterocolitis   0/261 (0.00%)  2/259 (0.77%)  2/211 (0.95%) 
Esophageal hemorrhage   0/261 (0.00%)  0/259 (0.00%)  1/211 (0.47%) 
Esophagitis   0/261 (0.00%)  0/259 (0.00%)  1/211 (0.47%) 
Fecal incontinence   0/261 (0.00%)  0/259 (0.00%)  1/211 (0.47%) 
Gastric hemorrhage   0/261 (0.00%)  1/259 (0.39%)  1/211 (0.47%) 
Gastritis   0/261 (0.00%)  0/259 (0.00%)  1/211 (0.47%) 
Gastrointestinal disorders-Other   0/261 (0.00%)  1/259 (0.39%)  1/211 (0.47%) 
Ileus   0/261 (0.00%)  0/259 (0.00%)  2/211 (0.95%) 
Jejunal obstruction   0/261 (0.00%)  0/259 (0.00%)  1/211 (0.47%) 
Lower gastrointestinal hemorrhage   0/261 (0.00%)  0/259 (0.00%)  1/211 (0.47%) 
Mucositis oral   0/261 (0.00%)  0/259 (0.00%)  3/211 (1.42%) 
Nausea   0/261 (0.00%)  0/259 (0.00%)  1/211 (0.47%) 
Typhlitis   1/261 (0.38%)  0/259 (0.00%)  7/211 (3.32%) 
Vomiting   1/261 (0.38%)  0/259 (0.00%)  1/211 (0.47%) 
General disorders       
Death NOS   2/261 (0.77%)  1/259 (0.39%)  1/211 (0.47%) 
Edema limbs   0/261 (0.00%)  0/259 (0.00%)  2/211 (0.95%) 
Edema trunk   0/261 (0.00%)  0/259 (0.00%)  1/211 (0.47%) 
Gait disturbance   0/261 (0.00%)  0/259 (0.00%)  1/211 (0.47%) 
General disorders and admin site conditions - Other   0/261 (0.00%)  1/259 (0.39%)  0/211 (0.00%) 
Multi-organ failure   1/261 (0.38%)  2/259 (0.77%)  4/211 (1.90%) 
Neck edema   0/261 (0.00%)  0/259 (0.00%)  1/211 (0.47%) 
Hepatobiliary disorders       
Cholecystitis   0/261 (0.00%)  0/259 (0.00%)  1/211 (0.47%) 
Hepatic failure   1/261 (0.38%)  0/259 (0.00%)  0/211 (0.00%) 
Hepatobiliary disorders-Other   1/261 (0.38%)  0/259 (0.00%)  1/211 (0.47%) 
Immune system disorders       
Allergic reaction   0/261 (0.00%)  0/259 (0.00%)  1/211 (0.47%) 
Infections and infestations       
Enterocolitis infectious   0/261 (0.00%)  0/259 (0.00%)  1/211 (0.47%) 
Infections and infestations-Other   0/261 (0.00%)  0/259 (0.00%)  5/211 (2.37%) 
Lip infection   0/261 (0.00%)  0/259 (0.00%)  1/211 (0.47%) 
Lung infection   0/261 (0.00%)  1/259 (0.39%)  4/211 (1.90%) 
Sepsis   1/261 (0.38%)  11/259 (4.25%)  17/211 (8.06%) 
Upper respiratory infection   0/261 (0.00%)  0/259 (0.00%)  1/211 (0.47%) 
Urinary tract infection   0/261 (0.00%)  0/259 (0.00%)  1/211 (0.47%) 
Investigations       
Activated partial thromboplastin time prolonged   0/261 (0.00%)  0/259 (0.00%)  1/211 (0.47%) 
Alanine aminotransferase increased   0/261 (0.00%)  0/259 (0.00%)  6/211 (2.84%) 
Alkaline phosphatase increased   0/261 (0.00%)  0/259 (0.00%)  2/211 (0.95%) 
Aspartate aminotransferase increased   0/261 (0.00%)  0/259 (0.00%)  5/211 (2.37%) 
Blood bilirubin increased   0/261 (0.00%)  1/259 (0.39%)  7/211 (3.32%) 
Cardiac troponin I increased   0/261 (0.00%)  1/259 (0.39%)  0/211 (0.00%) 
Creatinine increased   0/261 (0.00%)  0/259 (0.00%)  1/211 (0.47%) 
Ejection fraction decreased   0/261 (0.00%)  0/259 (0.00%)  3/211 (1.42%) 
Electrocardiogram QT corrected interval prolonged   0/261 (0.00%)  0/259 (0.00%)  1/211 (0.47%) 
Fibrinogen decreased   0/261 (0.00%)  0/259 (0.00%)  1/211 (0.47%) 
GGT increased   0/261 (0.00%)  0/259 (0.00%)  2/211 (0.95%) 
INR increased   0/261 (0.00%)  0/259 (0.00%)  1/211 (0.47%) 
Platelet count decreased   0/261 (0.00%)  0/259 (0.00%)  2/211 (0.95%) 
Weight gain   0/261 (0.00%)  0/259 (0.00%)  1/211 (0.47%) 
Weight loss   0/261 (0.00%)  0/259 (0.00%)  1/211 (0.47%) 
Metabolism and nutrition disorders       
Acidosis   0/261 (0.00%)  0/259 (0.00%)  2/211 (0.95%) 
Alkalosis   0/261 (0.00%)  0/259 (0.00%)  1/211 (0.47%) 
Anorexia   0/261 (0.00%)  0/259 (0.00%)  5/211 (2.37%) 
Dehydration   0/261 (0.00%)  0/259 (0.00%)  1/211 (0.47%) 
Hyperglycemia   0/261 (0.00%)  0/259 (0.00%)  3/211 (1.42%) 
Hypernatremia   0/261 (0.00%)  0/259 (0.00%)  2/211 (0.95%) 
Hypoalbuminemia   1/261 (0.38%)  0/259 (0.00%)  3/211 (1.42%) 
Hypocalcemia   1/261 (0.38%)  0/259 (0.00%)  4/211 (1.90%) 
Hypokalemia   1/261 (0.38%)  0/259 (0.00%)  6/211 (2.84%) 
Hyponatremia   1/261 (0.38%)  0/259 (0.00%)  2/211 (0.95%) 
Hypophosphatemia   0/261 (0.00%)  1/259 (0.39%)  2/211 (0.95%) 
Tumor lysis syndrome   0/261 (0.00%)  1/259 (0.39%)  4/211 (1.90%) 
Musculoskeletal and connective tissue disorders       
Back pain   0/261 (0.00%)  0/259 (0.00%)  1/211 (0.47%) 
Generalized muscle weakness   0/261 (0.00%)  0/259 (0.00%)  3/211 (1.42%) 
Musculoskeletal and connective tiss disorder - Other   0/261 (0.00%)  0/259 (0.00%)  1/211 (0.47%) 
Myalgia   0/261 (0.00%)  0/259 (0.00%)  1/211 (0.47%) 
Pain in extremity   0/261 (0.00%)  0/259 (0.00%)  1/211 (0.47%) 
Nervous system disorders       
Ataxia   0/261 (0.00%)  0/259 (0.00%)  1/211 (0.47%) 
Edema cerebral   0/261 (0.00%)  0/259 (0.00%)  1/211 (0.47%) 
Encephalopathy   0/261 (0.00%)  0/259 (0.00%)  1/211 (0.47%) 
Headache   1/261 (0.38%)  0/259 (0.00%)  0/211 (0.00%) 
Intracranial hemorrhage   0/261 (0.00%)  0/259 (0.00%)  2/211 (0.95%) 
Ischemia cerebrovascular   0/261 (0.00%)  0/259 (0.00%)  1/211 (0.47%) 
Nervous system disorders-Other   1/261 (0.38%)  1/259 (0.39%)  0/211 (0.00%) 
Paresthesia   0/261 (0.00%)  0/259 (0.00%)  1/211 (0.47%) 
Peripheral sensory neuropathy   0/261 (0.00%)  0/259 (0.00%)  1/211 (0.47%) 
Reversible posterior leukoencephalopathy syndrome   0/261 (0.00%)  0/259 (0.00%)  1/211 (0.47%) 
Seizure   1/261 (0.38%)  0/259 (0.00%)  2/211 (0.95%) 
Somnolence   0/261 (0.00%)  0/259 (0.00%)  1/211 (0.47%) 
Stroke   0/261 (0.00%)  0/259 (0.00%)  3/211 (1.42%) 
Vasovagal reaction   0/261 (0.00%)  0/259 (0.00%)  1/211 (0.47%) 
Renal and urinary disorders       
Acute kidney injury   2/261 (0.77%)  4/259 (1.54%)  9/211 (4.27%) 
Urinary incontinence   0/261 (0.00%)  0/259 (0.00%)  1/211 (0.47%) 
Reproductive system and breast disorders       
Genital edema   0/261 (0.00%)  0/259 (0.00%)  1/211 (0.47%) 
Respiratory, thoracic and mediastinal disorders       
Adult respiratory distress syndrome   1/261 (0.38%)  3/259 (1.16%)  4/211 (1.90%) 
Bronchopulmonary hemorrhage   0/261 (0.00%)  0/259 (0.00%)  2/211 (0.95%) 
Dyspnea   0/261 (0.00%)  1/259 (0.39%)  2/211 (0.95%) 
Hypoxia   0/261 (0.00%)  2/259 (0.77%)  5/211 (2.37%) 
Pleural effusion   0/261 (0.00%)  0/259 (0.00%)  2/211 (0.95%) 
Pulmonary edema   0/261 (0.00%)  1/259 (0.39%)  5/211 (2.37%) 
Resp, thoracic and mediastinal disorders - Other   0/261 (0.00%)  1/259 (0.39%)  1/211 (0.47%) 
Respiratory failure   3/261 (1.15%)  6/259 (2.32%)  15/211 (7.11%) 
Skin and subcutaneous tissue disorders       
Erythroderma   0/261 (0.00%)  0/259 (0.00%)  1/211 (0.47%) 
Rash maculo-papular   0/261 (0.00%)  0/259 (0.00%)  2/211 (0.95%) 
Vascular disorders       
Hematoma   0/261 (0.00%)  1/259 (0.39%)  0/211 (0.00%) 
Hypertension   0/261 (0.00%)  0/259 (0.00%)  3/211 (1.42%) 
Hypotension   0/261 (0.00%)  2/259 (0.77%)  8/211 (3.79%) 
Thromboembolic event   0/261 (0.00%)  0/259 (0.00%)  3/211 (1.42%) 
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Arm I (Standard Dose Cytarabine, Daunorubicin Hydrochloride) Arm II (High-dose Cytarabine, Idarubicin) Arm III (Vorinostat, High-dose Cytarabine, Idarubicin)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   249/261 (95.40%)   254/259 (98.07%)   206/211 (97.63%) 
Blood and lymphatic system disorders       
Anemia   185/261 (70.88%)  185/259 (71.43%)  137/211 (64.93%) 
Febrile neutropenia   158/261 (60.54%)  170/259 (65.64%)  120/211 (56.87%) 
Cardiac disorders       
Sinus bradycardia   11/261 (4.21%)  9/259 (3.47%)  12/211 (5.69%) 
Sinus tachycardia   44/261 (16.86%)  47/259 (18.15%)  30/211 (14.22%) 
Ear and labyrinth disorders       
Ear pain   16/261 (6.13%)  7/259 (2.70%)  2/211 (0.95%) 
Eye disorders       
Blurred vision   15/261 (5.75%)  13/259 (5.02%)  16/211 (7.58%) 
Eye disorders-Other   16/261 (6.13%)  15/259 (5.79%)  8/211 (3.79%) 
Gastrointestinal disorders       
Abdominal distension   13/261 (4.98%)  7/259 (2.70%)  11/211 (5.21%) 
Abdominal pain   59/261 (22.61%)  93/259 (35.91%)  76/211 (36.02%) 
Bloating   12/261 (4.60%)  16/259 (6.18%)  9/211 (4.27%) 
Colitis   5/261 (1.92%)  15/259 (5.79%)  10/211 (4.74%) 
Constipation   80/261 (30.65%)  47/259 (18.15%)  42/211 (19.91%) 
Diarrhea   129/261 (49.43%)  213/259 (82.24%)  157/211 (74.41%) 
Dry mouth   28/261 (10.73%)  19/259 (7.34%)  20/211 (9.48%) 
Dyspepsia   19/261 (7.28%)  14/259 (5.41%)  22/211 (10.43%) 
Dysphagia   21/261 (8.05%)  17/259 (6.56%)  14/211 (6.64%) 
Gastroesophageal reflux disease   16/261 (6.13%)  17/259 (6.56%)  14/211 (6.64%) 
Gastrointestinal disorders-Other   15/261 (5.75%)  19/259 (7.34%)  11/211 (5.21%) 
Hemorrhoids   16/261 (6.13%)  7/259 (2.70%)  17/211 (8.06%) 
Mucositis oral   95/261 (36.40%)  92/259 (35.52%)  66/211 (31.28%) 
Nausea   146/261 (55.94%)  181/259 (69.88%)  147/211 (69.67%) 
Oral hemorrhage   14/261 (5.36%)  2/259 (0.77%)  6/211 (2.84%) 
Oral pain   30/261 (11.49%)  22/259 (8.49%)  13/211 (6.16%) 
Typhlitis   10/261 (3.83%)  14/259 (5.41%)  18/211 (8.53%) 
Vomiting   69/261 (26.44%)  124/259 (47.88%)  93/211 (44.08%) 
General disorders       
Chills   47/261 (18.01%)  46/259 (17.76%)  37/211 (17.54%) 
Edema face   12/261 (4.60%)  13/259 (5.02%)  9/211 (4.27%) 
Edema limbs   71/261 (27.20%)  89/259 (34.36%)  45/211 (21.33%) 
Fatigue   138/261 (52.87%)  143/259 (55.21%)  105/211 (49.76%) 
Fever   77/261 (29.50%)  83/259 (32.05%)  55/211 (26.07%) 
General disorders and admin site conditions - Other   16/261 (6.13%)  29/259 (11.20%)  9/211 (4.27%) 
Infusion related reaction   15/261 (5.75%)  13/259 (5.02%)  6/211 (2.84%) 
Malaise   7/261 (2.68%)  13/259 (5.02%)  4/211 (1.90%) 
Non-cardiac chest pain   26/261 (9.96%)  20/259 (7.72%)  16/211 (7.58%) 
Pain   27/261 (10.34%)  34/259 (13.13%)  17/211 (8.06%) 
Infections and infestations       
Catheter related infection   6/261 (2.30%)  8/259 (3.09%)  12/211 (5.69%) 
Infections and infestations-Other   37/261 (14.18%)  46/259 (17.76%)  31/211 (14.69%) 
Lung infection   32/261 (12.26%)  34/259 (13.13%)  24/211 (11.37%) 
Sepsis   22/261 (8.43%)  20/259 (7.72%)  21/211 (9.95%) 
Injury, poisoning and procedural complications       
Bruising   11/261 (4.21%)  15/259 (5.79%)  9/211 (4.27%) 
Investigations       
Activated partial thromboplastin time prolonged   11/261 (4.21%)  19/259 (7.34%)  11/211 (5.21%) 
Alanine aminotransferase increased   99/261 (37.93%)  109/259 (42.08%)  87/211 (41.23%) 
Alkaline phosphatase increased   69/261 (26.44%)  70/259 (27.03%)  66/211 (31.28%) 
Aspartate aminotransferase increased   89/261 (34.10%)  108/259 (41.70%)  94/211 (44.55%) 
Blood bilirubin increased   68/261 (26.05%)  90/259 (34.75%)  72/211 (34.12%) 
Creatinine increased   20/261 (7.66%)  32/259 (12.36%)  35/211 (16.59%) 
INR increased   36/261 (13.79%)  53/259 (20.46%)  29/211 (13.74%) 
Investigations-Other   13/261 (4.98%)  20/259 (7.72%)  11/211 (5.21%) 
Lymphocyte count decreased   98/261 (37.55%)  113/259 (43.63%)  84/211 (39.81%) 
Neutrophil count decreased   155/261 (59.39%)  139/259 (53.67%)  112/211 (53.08%) 
Platelet count decreased   185/261 (70.88%)  180/259 (69.50%)  142/211 (67.30%) 
Weight loss   40/261 (15.33%)  37/259 (14.29%)  40/211 (18.96%) 
White blood cell decreased   163/261 (62.45%)  154/259 (59.46%)  121/211 (57.35%) 
Metabolism and nutrition disorders       
Anorexia   81/261 (31.03%)  103/259 (39.77%)  84/211 (39.81%) 
Hyperglycemia   92/261 (35.25%)  98/259 (37.84%)  89/211 (42.18%) 
Hyperkalemia   15/261 (5.75%)  21/259 (8.11%)  11/211 (5.21%) 
Hypermagnesemia   13/261 (4.98%)  17/259 (6.56%)  14/211 (6.64%) 
Hypernatremia   13/261 (4.98%)  16/259 (6.18%)  19/211 (9.00%) 
Hypoalbuminemia   127/261 (48.66%)  130/259 (50.19%)  99/211 (46.92%) 
Hypocalcemia   99/261 (37.93%)  109/259 (42.08%)  100/211 (47.39%) 
Hypoglycemia   6/261 (2.30%)  4/259 (1.54%)  11/211 (5.21%) 
Hypokalemia   109/261 (41.76%)  127/259 (49.03%)  98/211 (46.45%) 
Hypomagnesemia   41/261 (15.71%)  49/259 (18.92%)  39/211 (18.48%) 
Hyponatremia   93/261 (35.63%)  106/259 (40.93%)  68/211 (32.23%) 
Hypophosphatemia   71/261 (27.20%)  91/259 (35.14%)  69/211 (32.70%) 
Musculoskeletal and connective tissue disorders       
Back pain   36/261 (13.79%)  29/259 (11.20%)  24/211 (11.37%) 
Generalized muscle weakness   20/261 (7.66%)  15/259 (5.79%)  18/211 (8.53%) 
Neck pain   14/261 (5.36%)  6/259 (2.32%)  7/211 (3.32%) 
Pain in extremity   26/261 (9.96%)  25/259 (9.65%)  22/211 (10.43%) 
Nervous system disorders       
Dizziness   34/261 (13.03%)  22/259 (8.49%)  33/211 (15.64%) 
Dysgeusia   26/261 (9.96%)  38/259 (14.67%)  31/211 (14.69%) 
Headache   74/261 (28.35%)  70/259 (27.03%)  51/211 (24.17%) 
Psychiatric disorders       
Anxiety   41/261 (15.71%)  62/259 (23.94%)  35/211 (16.59%) 
Confusion   11/261 (4.21%)  16/259 (6.18%)  10/211 (4.74%) 
Depression   19/261 (7.28%)  28/259 (10.81%)  14/211 (6.64%) 
Insomnia   49/261 (18.77%)  51/259 (19.69%)  39/211 (18.48%) 
Renal and urinary disorders       
Acute kidney injury   9/261 (3.45%)  19/259 (7.34%)  26/211 (12.32%) 
Hematuria   14/261 (5.36%)  17/259 (6.56%)  21/211 (9.95%) 
Respiratory, thoracic and mediastinal disorders       
Cough   51/261 (19.54%)  48/259 (18.53%)  40/211 (18.96%) 
Dyspnea   55/261 (21.07%)  54/259 (20.85%)  40/211 (18.96%) 
Epistaxis   35/261 (13.41%)  37/259 (14.29%)  27/211 (12.80%) 
Hiccups   5/261 (1.92%)  14/259 (5.41%)  16/211 (7.58%) 
Hypoxia   10/261 (3.83%)  18/259 (6.95%)  13/211 (6.16%) 
Nasal congestion   20/261 (7.66%)  14/259 (5.41%)  12/211 (5.69%) 
Pleural effusion   16/261 (6.13%)  17/259 (6.56%)  19/211 (9.00%) 
Productive cough   10/261 (3.83%)  18/259 (6.95%)  9/211 (4.27%) 
Pulmonary edema   11/261 (4.21%)  15/259 (5.79%)  8/211 (3.79%) 
Resp, thoracic and mediastinal disorders - Other   7/261 (2.68%)  20/259 (7.72%)  10/211 (4.74%) 
Sore throat   34/261 (13.03%)  18/259 (6.95%)  18/211 (8.53%) 
Skin and subcutaneous tissue disorders       
Alopecia   46/261 (17.62%)  41/259 (15.83%)  46/211 (21.80%) 
Dry skin   16/261 (6.13%)  29/259 (11.20%)  22/211 (10.43%) 
Erythema multiforme   8/261 (3.07%)  13/259 (5.02%)  4/211 (1.90%) 
Periorbital edema   6/261 (2.30%)  14/259 (5.41%)  3/211 (1.42%) 
Pruritus   38/261 (14.56%)  58/259 (22.39%)  42/211 (19.91%) 
Purpura   11/261 (4.21%)  15/259 (5.79%)  6/211 (2.84%) 
Rash acneiform   11/261 (4.21%)  13/259 (5.02%)  9/211 (4.27%) 
Rash maculo-papular   94/261 (36.02%)  117/259 (45.17%)  82/211 (38.86%) 
Skin and subcutaneous tissue disorders - Other   29/261 (11.11%)  39/259 (15.06%)  25/211 (11.85%) 
Vascular disorders       
Hypertension   38/261 (14.56%)  54/259 (20.85%)  27/211 (12.80%) 
Hypotension   39/261 (14.94%)  45/259 (17.37%)  28/211 (13.27%) 
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Leukemia Committee Statistician
Organization: SWOG Statistics and Data Management Center
Phone: 206-667-4623
EMail: amoseley@fredhutch.org
Layout table for additonal information
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01802333     History of Changes
Other Study ID Numbers: NCI-2013-00490
NCI-2013-00490 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
S1203
PS1203_A06PAMDREVW01
SWOG-S1203
S1203 ( Other Identifier: SWOG )
S1203 ( Other Identifier: CTEP )
U10CA180888 ( U.S. NIH Grant/Contract )
U10CA032102 ( U.S. NIH Grant/Contract )
First Submitted: February 27, 2013
First Posted: March 1, 2013
Results First Submitted: May 21, 2018
Results First Posted: December 18, 2018
Last Update Posted: December 18, 2018