Genomic Predictors of Decitabine Response in Patients With Acute Myeloid Leukemia or Myelodysplastic Syndromes

• Sponsor: Washington University School of Medicine (Other)
• Overall Status: Completed
• CT.gov ID: NCT01687400
• Collaborator: (none)
• Enrollment: 114
• Location: 1
• Arm: 1
• Actual Duration (Months): 57
• Patients Per Site Per Month: 2

Study Details

Study Description

Brief Summary

This clinical trial studies potential genetic markers which might be used to predict which patients with acute myeloid leukemia or myelodysplastic syndromes respond to decitabine. This study will contribute to the efforts to find effective and less toxic therapies to provide durable remissions in a significant proportion of elderly AML patients.

Condition or Disease	Intervention/Treatment	Phase
Leukemia, Myeloid, Acute; Myelodysplastic Syndromes	Drug: decitabine	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 114 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Genomic Predictors of Decitabine Response in AML/MDS
• Actual Study Start Date: Feb 12, 2013
• Actual Primary Completion Date: Jun 23, 2017
• Actual Study Completion Date: Nov 13, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Decitabine Patients receive decitabine IV over 1 hour on days 1-10 of a 28-day cycle. Treatment continues for 2 cycles. Patients then receive decitabine IV over 1 hour on days 1-10, 1-5, or 1-3 (depending on response). Treatment continues in the absence of disease progression or unacceptable toxicity.	Drug: decitabine; Other Names: 5-aza-dCyd, 5AZA, DAC, Dacogen, deoxyazacytidine, dezocitidine

Outcome Measures

Primary Outcome Measures

1. Correlation of Patient Specific Mutations With Overall Response Rate [4 months (4 treatment cycles)]

   -Best response after 4 treatment cycles as assessed according to International Working Group (IWG) criteria; bone marrow for gene sequencing will be collected at baseline; mutations will be correlated with overall response rate --Complete remission (CR), Complete remission with incomplete hematologic recovery (CRi), Marrow complete remission (mCR), Partial remission (PR), Stable disease (SD), Progressive disease (PD)

Secondary Outcome Measures

1. Compare Outcomes of a 10-day Decitabine Per Cycle Regimen to a 5-day Regimen (Historical Controls) [4 months (4 treatment cycles)]

   The overall response rate (CR/CRi/mCR/PR) and complete response rate (CR/CRi/mCR) will be compared with historical controls. Response assessed according to IWG criteria.

2. Rate of Mutation Clearance During Treatment [Up to Day 56]

   Samples collected at baseline and after 10, 28 and 56 days of therapy; the rate of mutation clearance was measured as mean VAF change per day of treatment and was estimated using linear mixed model for repeated measurement data .

3. Peripheral Blood Decitabine Plasma Levels [Day 4]

   To determine whether steady state serum concentrations of decitabine correlated with responses Complete remission (CR), Complete remission with incomplete hematologic recovery (CRi), Partial remission (PR), Stable disease (SD), Progressive disease (PD), Not applicable (NA) - assessed according to International Working Group (IWG) criteria

4. Change in Bone Marrow Methylcytosine [Baseline and Day 10]

   -Change of total bone marrow deoxyribonucleic acid (DNA) methylcytosine from baseline to Day 10

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

All of the following:

• Patient must have non-M3 AML or MDS

• An adverse risk karyotype defined by:

• Complex karyotype by cytogenetics, or

• Deletion of all or part of chromosome 5, 7, 12, or 17 defined by FISH or cytogenetics, or

• Somatic TP53 mutation

All of the following:

1. Patient must have an ECOG performance status ≤ 2.

2. Patient must have >10% disease burden measured by cytomorphology, flow cytometry, or cytogenetics.

3. Patient must have peripheral white blood cell count < 50,000/mcl.

4. Patient must have adequate organ function, defined as:

5. Total bilirubin < 1.5 x ULN

6. AST/ALT < 2.5 x ULN

7. Serum creatinine < 2.0 x ULN

8. Patient must have undergone ≤ 2 cycles of prior hypomethylating agent (decitabine or azacitidine).

9. Patient must be enrolled in HRPO# 201011766 ("Tissue Acquisition for Analysis of Genetic Progression Factors in Hematologic Diseases").

10. Patient must be > 18 years of age.

11. Patient must be able to understand and willing to sign an IRB-approved written informed consent document.

Exclusion Criteria:

• Patient must not be pregnant or nursing

• Patient must not have acute promyelocytic leukemia or t(15;17) observed by FISH.

• Patient must not have known central nervous system (CNS) leukemia

• Patient must not have a history of positive human immunodeficiency virus (HIV) serology

• Patient must not have a history of positive hepatitis C serology

• Patient must not have undergone prior allogeneic stem cell transplant

• Patient must not have any uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, ongoing or active graft-versus-host disease (GVHD), congestive heart failure of New York Heart Association (NYHA) class 3 or 4, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements

• Patient must not have had radiation therapy within 14 days of enrollment

• Patient must not have received any chemotherapy within 21 days of enrollment and any acute treatment-related toxicities must have returned to baseline. Patients may be receiving hydrea at time of enrollment.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Washington University School of Medicine	Saint Louis	Missouri	United States	63110

Sponsors and Collaborators

• Washington University School of Medicine

Investigators

• Principal Investigator: Welch John, M.D., Ph.D., Washington University School of Medicine

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 15, 2016

More Information

Additional Information:

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Publications

None provided.

• Responsible Party: Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT01687400
• Other Study ID Numbers: 201210102
• First Posted: Sep 18, 2012
• Last Update Posted: Oct 2, 2018
• Last Verified: Sep 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Leukemia; Preleukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Syndrome; Decitabine

Study Results

Participant Flow

Recruitment Details	The study opened to participant enrollment on 02/12/2013 and closed to participant enrollment on 06/19/2017.

Arm/Group Title	Decitabine
Arm/Group Description	Patients receive decitabine IV over 1 hour on days 1-10 of a 28-day cycle. Treatment continues for 2 cycles. Patients then receive decitabine IV over 1 hour on days 1-10, 1-5, or 1-3 (depending on response). Treatment continues in the absence of disease progression or unacceptable toxicity.
Period Title: Overall Study
STARTED	114
COMPLETED	114
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Decitabine
Arm/Group Description	Patients receive decitabine IV over 1 hour on days 1-10 of a 28-day cycle. Treatment continues for 2 cycles. Patients then receive decitabine IV over 1 hour on days 1-10, 1-5, or 1-3 (depending on response). Treatment continues in the absence of disease progression or unacceptable toxicity.
Overall Participants	114
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	73
Sex: Female, Male (Count of Participants)
Female	48 42.1%
Male	66 57.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 0.9%
Not Hispanic or Latino	90 78.9%
Unknown or Not Reported	23 20.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	2 1.8%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	6 5.3%
White	105 92.1%
More than one race	0 0%
Unknown or Not Reported	1 0.9%
Region of Enrollment (participants) [Number]
United States	114 100%

Outcome Measures

1. Primary Outcome

Title	Correlation of Patient Specific Mutations With Overall Response Rate
Description	-Best response after 4 treatment cycles as assessed according to International Working Group (IWG) criteria; bone marrow for gene sequencing will be collected at baseline; mutations will be correlated with overall response rate --Complete remission (CR), Complete remission with incomplete hematologic recovery (CRi), Marrow complete remission (mCR), Partial remission (PR), Stable disease (SD), Progressive disease (PD)
Time Frame	4 months (4 treatment cycles)

Outcome Measure Data

Analysis Population Description

-Some participants were not evaluable for this outcome measure due to sample collection quality issues and if they had repeat bone marrow biopsies and could be evaluated for responses.

Arm/Group Title	Decitabine (Participants With Response of CR/CRi/mCR/PR)	Decitabine (Participants With Response of SD/PD)
Arm/Group Description	Patients receive decitabine IV over 1 hour on days 1-10 of a 28-day cycle. Treatment continues for 2 cycles. Patients then receive decitabine IV over 1 hour on days 1-10, 1-5, or 1-3 (depending on response). Treatment continues in the absence of disease progression or unacceptable toxicity.	Patients receive decitabine IV over 1 hour on days 1-10 of a 28-day cycle. Treatment continues for 2 cycles. Patients then receive decitabine IV over 1 hour on days 1-10, 1-5, or 1-3 (depending on response). Treatment continues in the absence of disease progression or unacceptable toxicity.
Measure Participants	64	22
TP53	26 22.8%	3 NaN
ASXL1	9 7.9%	2 NaN
SRSF2	7 6.1%	5 NaN
IDH2	6 5.3%	5 NaN
DNMT3A	8 7%	5 NaN
SF3B1	7 6.1%	0 NaN
RUNX1	5 4.4%	3 NaN
TET2	4 3.5%	3 NaN
IDH1	2 1.8%	3 NaN
NPM1	4 3.5%	1 NaN
NRAS	3 2.6%	3 NaN
U2AF1	4 3.5%	1 NaN
MY05B	3 2.6%	2 NaN
WT1	5 4.4%	1 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Decitabine (Participants With Response of CR/CRi/mCR/PR), Decitabine (Participants With Response of SD/PD)
	Comments	Statistical analysis #1 is for the genetic mutation TP53.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.035
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Decitabine (Participants With Response of CR/CRi/mCR/PR), Decitabine (Participants With Response of SD/PD)
	Comments	Statistical analysis #2 is for ASXL1 genetic mutation
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.72
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Decitabine (Participants With Response of CR/CRi/mCR/PR), Decitabine (Participants With Response of SD/PD)
	Comments	Statistical analysis #3 is for SRSF2 genetic mutation
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.28
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Decitabine (Participants With Response of CR/CRi/mCR/PR), Decitabine (Participants With Response of SD/PD)
	Comments	Statistical analysis #4 is for IDH2 genetic mutation
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.14
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Decitabine (Participants With Response of CR/CRi/mCR/PR), Decitabine (Participants With Response of SD/PD)
	Comments	Statistical analysis #5 is for DNMT3A genetic mutation
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Decitabine (Participants With Response of CR/CRi/mCR/PR), Decitabine (Participants With Response of SD/PD)
	Comments	Statistical analysis #6 is for SF3B1 genetic mutation
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.183
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Decitabine (Participants With Response of CR/CRi/mCR/PR), Decitabine (Participants With Response of SD/PD)
	Comments	Statistical analysis #7 is for RUNX1 genetic mutation
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.42
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Decitabine (Participants With Response of CR/CRi/mCR/PR), Decitabine (Participants With Response of SD/PD)
	Comments	Statistical analysis #8 is for TET2 genetic mutation
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.36
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Decitabine (Participants With Response of CR/CRi/mCR/PR), Decitabine (Participants With Response of SD/PD)
	Comments	Statistical analysis #9 is for IDH1 genetic mutation
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Decitabine (Participants With Response of CR/CRi/mCR/PR), Decitabine (Participants With Response of SD/PD)
	Comments	Statistical analysis #10 is for NPM1 genetic mutation
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	1
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Decitabine (Participants With Response of CR/CRi/mCR/PR), Decitabine (Participants With Response of SD/PD)
	Comments	Statistical analysis #11 is for NRAS genetic mutation
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.17
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Decitabine (Participants With Response of CR/CRi/mCR/PR), Decitabine (Participants With Response of SD/PD)
	Comments	-Statistical analysis #12 is for U2AF1 genetic mutation
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	1
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Decitabine (Participants With Response of CR/CRi/mCR/PR), Decitabine (Participants With Response of SD/PD)
	Comments	Statistical analysis #13 is for MY05B genetic mutation
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Decitabine (Participants With Response of CR/CRi/mCR/PR), Decitabine (Participants With Response of SD/PD)
	Comments	Statistical analysis #14 is for WT1 genetic mutation
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	1
	Comments
	Method	Fisher Exact
	Comments

2. Secondary Outcome

Title	Compare Outcomes of a 10-day Decitabine Per Cycle Regimen to a 5-day Regimen (Historical Controls)
Description	The overall response rate (CR/CRi/mCR/PR) and complete response rate (CR/CRi/mCR) will be compared with historical controls. Response assessed according to IWG criteria.
Time Frame	4 months (4 treatment cycles)

Outcome Measure Data

Analysis Population Description

-Participants were evaluable for this outcome measure if they completed at least one cycle of treatment and the cycle 1 day 28 bone marrow biopsy to assess response

Arm/Group Title	Decitabine
Arm/Group Description	Patients receive decitabine IV over 1 hour on days 1-10 of a 28-day cycle. Treatment continues for 2 cycles. Patients then receive decitabine IV over 1 hour on days 1-10, 1-5, or 1-3 (depending on response). Treatment continues in the absence of disease progression or unacceptable toxicity.
Measure Participants	98
Overall response rate (CR, CRi/mCR/PR)	74.42 65.3%
Complete response rate (CR, CRi, mCR)	63.95 56.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Decitabine (Participants With Response of CR/CRi/mCR/PR)
	Comments	-The historical control of a 5-day regimen (Cashen et al 2010 JCO = NCT00358644) showed 25% (14 out of 55 participants) in overall response rate
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Chi-squared
	Comments	1-sample Chi-square test to compare the overall response rate (ORR) to historical control (with ORR=0.25)
Method of Estimation	Estimation Parameter	Overall Response Rate-for current study
	Estimated Value	0.744
	Confidence Interval	(2-Sided) 95%; 0.652 to 0.836
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Decitabine (Participants With Response of CR/CRi/mCR/PR)
	Comments	-The historical control of a 5-day regimen (Cashen et al 2010 JCO = NCT00358644) showed 24% (13 out of 55 participants) in complete response rate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Chi-squared
	Comments	1-sample Chi-square test to compare the complete response rate to historical control (with CR=0.24)
Method of Estimation	Estimation Parameter	Complete response rate-for current study
	Estimated Value	0.640
	Confidence Interval	(2-Sided) 95%; 0.538 to 0.741
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Rate of Mutation Clearance During Treatment
Description	Samples collected at baseline and after 10, 28 and 56 days of therapy; the rate of mutation clearance was measured as mean VAF change per day of treatment and was estimated using linear mixed model for repeated measurement data .
Time Frame	Up to Day 56

Outcome Measure Data

Analysis Population Description

-The first 39 cases with adequate samples were serially evaluated with enhanced exome sequencing. The investigators evaluated 15 additional cases using gene panel sequencing.

Arm/Group Title	Decitabine
Arm/Group Description	Patients receive decitabine IV over 1 hour on days 1-10 of a 28-day cycle. Treatment continues for 2 cycles. Patients then receive decitabine IV over 1 hour on days 1-10, 1-5, or 1-3 (depending on response). Treatment continues in the absence of disease progression or unacceptable toxicity.
Measure Participants	54
TP53	-0.781 (0.4423)
SRSF2	-0.2214 (0.2705)
DNMT3A	-0.2122 (0.2817)
IDH2	-0.08344 (0.2841)
RUNX1	-0.2641 (0.6536)
TET2	-0.07478 (0.3164)
ASXL1	-0.3898 (0.3791)
IDH1	-0.1103 (0.196)
NRAS	0.04544 (0.2554)
SF3B1	-0.719 (0.3481)

4. Secondary Outcome

Title	Peripheral Blood Decitabine Plasma Levels
Description	To determine whether steady state serum concentrations of decitabine correlated with responses Complete remission (CR), Complete remission with incomplete hematologic recovery (CRi), Partial remission (PR), Stable disease (SD), Progressive disease (PD), Not applicable (NA) - assessed according to International Working Group (IWG) criteria
Time Frame	Day 4

Outcome Measure Data

Analysis Population Description

The first 45 participants enrolled with adequate samples were analyzed using GC-MS quantification of serum decitabine levels. Sufficient funds were lacking to complete the analysis of additional participants and all participants with data analyzed are reported.

Arm/Group Title	Decitabine
Arm/Group Description	Patients receive decitabine IV over 1 hour on days 1-10 of a 28-day cycle. Treatment continues for 2 cycles. Patients then receive decitabine IV over 1 hour on days 1-10, 1-5, or 1-3 (depending on response). Treatment continues in the absence of disease progression or unacceptable toxicity.
Measure Participants	45
CR	140.5 (53.41)
CRi	117.2 (54.6)
PR	67.71 (56.18)
SD	145 (73.06)
PD	298.5 (213.3)
NA	99.64 (58.4)

5. Secondary Outcome

Title	Change in Bone Marrow Methylcytosine
Description	-Change of total bone marrow deoxyribonucleic acid (DNA) methylcytosine from baseline to Day 10
Time Frame	Baseline and Day 10

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Decitabine (CR/CRi/mCR)	Decitabine (PR/SD/PD)
Arm/Group Description	Patients receive decitabine IV over 1 hour on days 1-10 of a 28-day cycle. Treatment continues for 2 cycles. Patients then receive decitabine IV over 1 hour on days 1-10, 1-5, or 1-3 (depending on response). Treatment continues in the absence of disease progression or unacceptable toxicity.	Patients receive decitabine IV over 1 hour on days 1-10 of a 28-day cycle. Treatment continues for 2 cycles. Patients then receive decitabine IV over 1 hour on days 1-10, 1-5, or 1-3 (depending on response). Treatment continues in the absence of disease progression or unacceptable toxicity.
Measure Participants	14	11
Day 0	0.53 (0)	0.5374 (0)
Day 10	0.4416 (0.0247)	0.4639 (0.035)

Adverse Events

Time Frame	-Adverse events were collected from the start of treatment until 30 days following the last day of study treatment (average 5 months) -All deaths were collected from enrollment through study completion date.
Adverse Event Reporting Description	Grades 1-5 adverse events will be recorded for the first 50 enrolled participants. Grades 3-5 will be recorded for the remainder of enrolled participants (n=64).
Arm/Group Title	Decitabine (First 50 Enrolled Patients)		Decitabine (Remainder of Enrolled Patients n=64)
Arm/Group Description	Patients receive decitabine IV over 1 hour on days 1-10 of a 28-day cycle. Treatment continues for 2 cycles. Patients then receive decitabine IV over 1 hour on days 1-10, 1-5, or 1-3 (depending on response). Treatment continues in the absence of disease progression or unacceptable toxicity.		Patients receive decitabine IV over 1 hour on days 1-10 of a 28-day cycle. Treatment continues for 2 cycles. Patients then receive decitabine IV over 1 hour on days 1-10, 1-5, or 1-3 (depending on response). Treatment continues in the absence of disease progression or unacceptable toxicity.
All Cause Mortality
	Decitabine (First 50 Enrolled Patients)		Decitabine (Remainder of Enrolled Patients n=64)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	38/50 (76%)		43/64 (67.2%)
Serious Adverse Events
	Decitabine (First 50 Enrolled Patients)		Decitabine (Remainder of Enrolled Patients n=64)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	42/50 (84%)		47/64 (73.4%)
Blood and lymphatic system disorders
Febrile neutropenia	23/50 (46%)		30/64 (46.9%)
Cardiac disorders
Atrial fibrillation	1/50 (2%)		1/64 (1.6%)
Atrial flutter	0/50 (0%)		1/64 (1.6%)
Cardiac arrest	1/50 (2%)		0/64 (0%)
Heart failure	0/50 (0%)		1/64 (1.6%)
NSTEMI	0/50 (0%)		1/64 (1.6%)
Pericardial effusion	1/50 (2%)		0/64 (0%)
STEMI	0/50 (0%)		2/64 (3.1%)
Eye disorders
Central retinal venous occlusion	1/50 (2%)		0/64 (0%)
Gastrointestinal disorders
Colitis	0/50 (0%)		3/64 (4.7%)
Constipation	0/50 (0%)		2/64 (3.1%)
Diarrhea	1/50 (2%)		2/64 (3.1%)
Hematemesis	1/50 (2%)		1/64 (1.6%)
Ileus	1/50 (2%)		0/64 (0%)
Mucositis - oral	0/50 (0%)		1/64 (1.6%)
General disorders
Edema	1/50 (2%)		0/64 (0%)
Failure to thrive	0/50 (0%)		1/64 (1.6%)
Fever	1/50 (2%)		0/64 (0%)
Infusion related reaction	2/50 (4%)		1/64 (1.6%)
Malaise	1/50 (2%)		0/64 (0%)
Pain	1/50 (2%)		0/64 (0%)
Progressive disease/death	5/50 (10%)		2/64 (3.1%)
Infections and infestations
Bacteremia - Coagulase negative staphylococcus	0/50 (0%)		2/64 (3.1%)
Bacteremia - E. coli	0/50 (0%)		2/64 (3.1%)
Bacteremia - ESBL E. coli	1/50 (2%)		0/64 (0%)
Bacteremia - Enterococcus faecium	1/50 (2%)		0/64 (0%)
Bacteremia - Klebsiella pneumoniae	0/50 (0%)		1/64 (1.6%)
Bacteremia - Micrococcus	0/50 (0%)		1/64 (1.6%)
Bacteremia - Staphylococcus capitis	0/50 (0%)		1/64 (1.6%)
Bacteremia - Staphylococcus epidermis	0/50 (0%)		1/64 (1.6%)
Bacteremia - Staphylococcus infection	0/50 (0%)		1/64 (1.6%)
Bacteremia - Streptococcus	0/50 (0%)		2/64 (3.1%)
Bacteremia - Streptococcus mitis	0/50 (0%)		4/64 (6.3%)
Bacteremia - VRE	0/50 (0%)		1/64 (1.6%)
Bacteremia - gram negative	1/50 (2%)		0/64 (0%)
Bone infection - Osteomyelitis	1/50 (2%)		0/64 (0%)
C. difficile	0/50 (0%)		2/64 (3.1%)
Catheter related infection	4/50 (8%)		2/64 (3.1%)
Cellulitis infection/pneumonia infection	0/50 (0%)		1/64 (1.6%)
Dental infection	1/50 (2%)		0/64 (0%)
Diverticulitis	0/50 (0%)		1/64 (1.6%)
Diverticulitis infection	0/50 (0%)		2/64 (3.1%)
Endovascular infection	0/50 (0%)		1/64 (1.6%)
Fusarium fungemia infection	0/50 (0%)		1/64 (1.6%)
Iletitis	0/50 (0%)		1/64 (1.6%)
Lung infection	4/50 (8%)		14/64 (21.9%)
Parainfluenza infection	1/50 (2%)		0/64 (0%)
Sepsis	3/50 (6%)		7/64 (10.9%)
Septic arthritis	1/50 (2%)		0/64 (0%)
Sinusitis	0/50 (0%)		2/64 (3.1%)
Skin infection	3/50 (6%)		5/64 (7.8%)
Submandicular sialadenitis infection	0/50 (0%)		1/64 (1.6%)
Tooth infection	2/50 (4%)		0/64 (0%)
Upper respiratory infection	0/50 (0%)		2/64 (3.1%)
Upper respiratory infection - parainfluenza	1/50 (2%)		0/64 (0%)
Urinary tract infection	1/50 (2%)		3/64 (4.7%)
Bacteremia - Streptococcus mitis/oralis	0/50 (0%)		1/64 (1.6%)
Injury, poisoning and procedural complications
Fall	2/50 (4%)		1/64 (1.6%)
Investigations
White blood cell count decreased	0/50 (0%)		1/64 (1.6%)
Metabolism and nutrition disorders
Hyponatremia	1/50 (2%)		0/64 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/50 (0%)		1/64 (1.6%)
Back pain	1/50 (2%)		0/64 (0%)
Myositis	0/50 (0%)		1/64 (1.6%)
Nervous system disorders
Intracranial hemorrhage	0/50 (0%)		1/64 (1.6%)
Stroke	1/50 (2%)		1/64 (1.6%)
Psychiatric disorders
Confusion	1/50 (2%)		0/64 (0%)
Renal and urinary disorders
Acute kidney injury	2/50 (4%)		0/64 (0%)
Hematuria	1/50 (2%)		1/64 (1.6%)
Respiratory, thoracic and mediastinal disorders
Acute hypoxemic respiratory failure	0/50 (0%)		1/64 (1.6%)
Dyspnea	1/50 (2%)		0/64 (0%)
Epistaxis	0/50 (0%)		5/64 (7.8%)
Pleural effusion	1/50 (2%)		1/64 (1.6%)
Pulmonary embolism	0/50 (0%)		2/64 (3.1%)
Respiratory failure	1/50 (2%)		1/64 (1.6%)
Respiratory syncytial virus	0/50 (0%)		1/64 (1.6%)
Skin and subcutaneous tissue disorders
Rash maculo-papular	1/50 (2%)		2/64 (3.1%)
Sweet's syndrome	1/50 (2%)		1/64 (1.6%)
Vascular disorders
Hematoma	0/50 (0%)		1/64 (1.6%)
Hypotension	1/50 (2%)		1/64 (1.6%)
Thromboembolic event	3/50 (6%)		2/64 (3.1%)
Other (Not Including Serious) Adverse Events
	Decitabine (First 50 Enrolled Patients)		Decitabine (Remainder of Enrolled Patients n=64)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	50/50 (100%)		64/64 (100%)
Blood and lymphatic system disorders
Anemia	14/50 (28%)		22/64 (34.4%)
Febrile neutropenia	16/50 (32%)		13/64 (20.3%)
Lymph node pain	1/50 (2%)		0/64 (0%)
Submandibular lymphadenopathy	1/50 (2%)		0/64 (0%)
Cardiac disorders
Atrial fibrillation	4/50 (8%)		4/64 (6.3%)
Atrial flutter	1/50 (2%)		0/64 (0%)
Chest pain	2/50 (4%)		0/64 (0%)
Electrocardiogram QT corrected interval prolonged	1/50 (2%)		0/64 (0%)
Heart failure	1/50 (2%)		2/64 (3.1%)
Left ventricular systolic dysfunction	1/50 (2%)		1/64 (1.6%)
Myocardial infarction	2/50 (4%)		1/64 (1.6%)
Palpitations	2/50 (4%)		0/64 (0%)
Pericardial effusion	4/50 (8%)		0/64 (0%)
Pericardial tamponade	1/50 (2%)		0/64 (0%)
Sinus bradycardia	5/50 (10%)		0/64 (0%)
Sinus tachycardia	18/50 (36%)		0/64 (0%)
Supraventricular tachycardia	2/50 (4%)		1/64 (1.6%)
Ventricular ectopy	0/50 (0%)		1/64 (1.6%)
Ear and labyrinth disorders
Ear congestion	2/50 (4%)		0/64 (0%)
Ear pain	1/50 (2%)		0/64 (0%)
Hearing impaired	1/50 (2%)		0/64 (0%)
Eye disorders
Blurred vision	4/50 (8%)		0/64 (0%)
Conjunctivitis	1/50 (2%)		0/64 (0%)
Diplopia	1/50 (2%)		0/64 (0%)
Dry eye	1/50 (2%)		0/64 (0%)
Floaters	1/50 (2%)		0/64 (0%)
Photophobia	1/50 (2%)		0/64 (0%)
Vision changes unspecified	1/50 (2%)		0/64 (0%)
Vision loss partial (temporary)	1/50 (2%)		0/64 (0%)
Gastrointestinal disorders
Abdominal pain	12/50 (24%)		0/64 (0%)
Anal mucositis	1/50 (2%)		0/64 (0%)
Bloating	1/50 (2%)		0/64 (0%)
Burping	1/50 (2%)		0/64 (0%)
Constipation	25/50 (50%)		0/64 (0%)
Dental caries	1/50 (2%)		0/64 (0%)
Diarrhea	26/50 (52%)		0/64 (0%)
Diverticulitis	0/50 (0%)		2/64 (3.1%)
Diverticulosis	1/50 (2%)		0/64 (0%)
Dry mouth	2/50 (4%)		0/64 (0%)
Dyspepsia	3/50 (6%)		0/64 (0%)
Dysphagia	5/50 (10%)		1/64 (1.6%)
Esophagitis	1/50 (2%)		0/64 (0%)
Fecal incontinence	4/50 (8%)		0/64 (0%)
Gastric hemorrhage	1/50 (2%)		0/64 (0%)
Gastrointestinal pain	1/50 (2%)		0/64 (0%)
Hiatal hernia	3/50 (6%)		0/64 (0%)
Hypothermia	1/50 (2%)		0/64 (0%)
Ileus	1/50 (2%)		0/64 (0%)
Lower gastrointestinal hemorrhage	1/50 (2%)		0/64 (0%)
Mucositis - oral	33/50 (66%)		2/64 (3.1%)
Nausea	28/50 (56%)		1/64 (1.6%)
Oral hemorrhage	3/50 (6%)		1/64 (1.6%)
Oral pain	5/50 (10%)		0/64 (0%)
Pancreatic cyst	1/50 (2%)		0/64 (0%)
Pancreatitis	0/50 (0%)		1/64 (1.6%)
Small bowel obstruction	1/50 (2%)		0/64 (0%)
Toothache	3/50 (6%)		1/64 (1.6%)
Typhlitis	0/50 (0%)		1/64 (1.6%)
Vomiting	19/50 (38%)		0/64 (0%)
General disorders
Chills	31/50 (62%)		0/64 (0%)
Edema face	2/50 (4%)		0/64 (0%)
Edema limbs	31/50 (62%)		2/64 (3.1%)
Facial pain	1/50 (2%)		0/64 (0%)
Fatigue	26/50 (52%)		7/64 (10.9%)
Fever	2/50 (4%)		0/64 (0%)
Gait disturbance	1/50 (2%)		0/64 (0%)
Infusion related reaction	9/50 (18%)		1/64 (1.6%)
Irritability	1/50 (2%)		0/64 (0%)
Localized edema	1/50 (2%)		0/64 (0%)
Malaise	3/50 (6%)		0/64 (0%)
Non-cardiac chest pain	7/50 (14%)		0/64 (0%)
Pain	15/50 (30%)		1/64 (1.6%)
Immune system disorders
Allergic reaction	5/50 (10%)		0/64 (0%)
Infections and infestations
Bacteremia (Gram negative)	1/50 (2%)		0/64 (0%)
Bacteremia - Escherichia coli/Pseudomonus aeruginosa	1/50 (2%)		0/64 (0%)
Bacteremia - Myobacterium abscessus	1/50 (2%)		0/64 (0%)
Bacteremia - Pseudomonas aeruginosa	1/50 (2%)		1/64 (1.6%)
Bacteremia - Staphylococcus epidermidis	2/50 (4%)		1/64 (1.6%)
Bacteremia - Streptococcus mitis	0/50 (0%)		3/64 (4.7%)
Bacteremia - Streptococcus mitis/Coagulase negative staphylococcus	0/50 (0%)		1/64 (1.6%)
C. difficile	2/50 (4%)		0/64 (0%)
Candidal intertrigo (genital)	1/50 (2%)		0/64 (0%)
Catheter related infection	4/50 (8%)		6/64 (9.4%)
Fungal abscess brain	0/50 (0%)		1/64 (1.6%)
Fungal infection - spleen and liver	0/50 (0%)		1/64 (1.6%)
Gastroenteritis (viral)	2/50 (4%)		0/64 (0%)
Gum infection	1/50 (2%)		0/64 (0%)
HSV infection	1/50 (2%)		0/64 (0%)
Infection mouth lesion	1/50 (2%)		0/64 (0%)
Infective myositis	0/50 (0%)		1/64 (1.6%)
Joint infection	0/50 (0%)		1/64 (1.6%)
Lung infection	17/50 (34%)		10/64 (15.6%)
Oral buccosal infection	1/50 (2%)		0/64 (0%)
Oral thrush	13/50 (26%)		0/64 (0%)
Otitis externa	1/50 (2%)		0/64 (0%)
Perineal folliculitis	0/50 (0%)		1/64 (1.6%)
Preseptal cellulitis	0/50 (0%)		2/64 (3.1%)
Salivary gland infection	0/50 (0%)		1/64 (1.6%)
Sepsis	9/50 (18%)		1/64 (1.6%)
Septic arthritis	1/50 (2%)		0/64 (0%)
Sinusitis	4/50 (8%)		1/64 (1.6%)
Skin infection	17/50 (34%)		1/64 (1.6%)
Tooth infection	4/50 (8%)		0/64 (0%)
Upper respiratory infection	4/50 (8%)		0/64 (0%)
Urinary tract infection	2/50 (4%)		0/64 (0%)
Vaginal infection	1/50 (2%)		0/64 (0%)
Injury, poisoning and procedural complications
Bruising	21/50 (42%)		0/64 (0%)
Burn	1/50 (2%)		0/64 (0%)
Fall	9/50 (18%)		2/64 (3.1%)
Fracture	2/50 (4%)		0/64 (0%)
Hemorrhage from bronchoscopy	0/50 (0%)		1/64 (1.6%)
Hip pain following bone marrow biopsy	0/50 (0%)		1/64 (1.6%)
Postoperative hemmorhage	3/50 (6%)		0/64 (0%)
Skin abrasion	2/50 (4%)		0/64 (0%)
Investigations
Activated partial thromboplastin time prolonged	19/50 (38%)		5/64 (7.8%)
Alanine aminotransferase increased	30/50 (60%)		2/64 (3.1%)
Alkaline phosphatase increased	19/50 (38%)		1/64 (1.6%)
Aspartate aminotransferase increased	26/50 (52%)		2/64 (3.1%)
Blood bilirubin increased	19/50 (38%)		0/64 (0%)
Cardiac troponin I increased	3/50 (6%)		0/64 (0%)
Cardiac troponin T increased	1/50 (2%)		0/64 (0%)
Creatinine increased	8/50 (16%)		0/64 (0%)
Electrocardiogram QT corrected interval prolonged	6/50 (12%)		3/64 (4.7%)
INR increased	28/50 (56%)		0/64 (0%)
Lymphocyte count decreased	44/50 (88%)		45/64 (70.3%)
Lymphocyte count increased	0/50 (0%)		1/64 (1.6%)
Neutrophil count decreased	20/50 (40%)		38/64 (59.4%)
Platelet count decreased	27/50 (54%)		47/64 (73.4%)
Weight gain	1/50 (2%)		0/64 (0%)
Weight loss	21/50 (42%)		0/64 (0%)
White blood cell decreased	43/50 (86%)		54/64 (84.4%)
Metabolism and nutrition disorders
Acidosis	1/50 (2%)		0/64 (0%)
Anorexia	22/50 (44%)		2/64 (3.1%)
Dehydration	15/50 (30%)		6/64 (9.4%)
Hypercalcemia	3/50 (6%)		0/64 (0%)
Hyperglycemia	8/50 (16%)		13/64 (20.3%)
Hyperkalemia	9/50 (18%)		0/64 (0%)
Hypermagnesemia	5/50 (10%)		1/64 (1.6%)
Hypernatremia	7/50 (14%)		1/64 (1.6%)
Hyperuricemia	1/50 (2%)		1/64 (1.6%)
Hypoalbuminemia	39/50 (78%)		2/64 (3.1%)
Hypocalcemia	29/50 (58%)		1/64 (1.6%)
Hypokalemia	29/50 (58%)		14/64 (21.9%)
Hypomagnesemia	7/50 (14%)		0/64 (0%)
Hyponatremia	37/50 (74%)		12/64 (18.8%)
Hypophosphatemia	28/50 (56%)		13/64 (20.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	10/50 (20%)		0/64 (0%)
Back pain	10/50 (20%)		1/64 (1.6%)
Bone pain	2/50 (4%)		0/64 (0%)
Bone spur	1/50 (2%)		0/64 (0%)
Degenerative disc disease	1/50 (2%)		0/64 (0%)
Flank pain	0/50 (0%)		1/64 (1.6%)
Generalized muscle weakness	24/50 (48%)		6/64 (9.4%)
Hand cramps	2/50 (4%)		0/64 (0%)
Joint effusion	0/50 (0%)		1/64 (1.6%)
Muscle cramps	1/50 (2%)		0/64 (0%)
Myalgia	3/50 (6%)		0/64 (0%)
Neck pain	2/50 (4%)		0/64 (0%)
Pain in extremity	10/50 (20%)		1/64 (1.6%)
Nervous system disorders
Burning sensation	1/50 (2%)		0/64 (0%)
Cognitive impairment acute worsening from baseline	0/50 (0%)		1/64 (1.6%)
Dizziness	15/50 (30%)		1/64 (1.6%)
Dysarthria	1/50 (2%)		0/64 (0%)
Dysgeusia	3/50 (6%)		0/64 (0%)
Encephalopathy	3/50 (6%)		1/64 (1.6%)
Facial muscle weakness	1/50 (2%)		0/64 (0%)
Headache	16/50 (32%)		0/64 (0%)
Lethargy	13/50 (26%)		0/64 (0%)
Neuralgia	1/50 (2%)		0/64 (0%)
Paresthesia	2/50 (4%)		0/64 (0%)
Peripheral motor neuropathy	0/50 (0%)		1/64 (1.6%)
Peripheral sensory neuropathy	3/50 (6%)		0/64 (0%)
Presyncope	1/50 (2%)		0/64 (0%)
Restless leg syndrome	2/50 (4%)		0/64 (0%)
Seizure	1/50 (2%)		0/64 (0%)
Sinus pain	2/50 (4%)		0/64 (0%)
Somnolence	7/50 (14%)		0/64 (0%)
Stroke	1/50 (2%)		1/64 (1.6%)
Syncope	0/50 (0%)		2/64 (3.1%)
Tremor	2/50 (4%)		0/64 (0%)
Psychiatric disorders
Agitation	2/50 (4%)		0/64 (0%)
Altered mental status	1/50 (2%)		0/64 (0%)
Anxiety	3/50 (6%)		0/64 (0%)
Confusion	17/50 (34%)		1/64 (1.6%)
Delirium	2/50 (4%)		0/64 (0%)
Depression	5/50 (10%)		0/64 (0%)
Hallucinations	3/50 (6%)		0/64 (0%)
Insomnia	9/50 (18%)		0/64 (0%)
Restlessness	1/50 (2%)		0/64 (0%)
Renal and urinary disorders
Acute kidney injury	7/50 (14%)		0/64 (0%)
Acute renal failure	0/50 (0%)		2/64 (3.1%)
Bladder spasm	1/50 (2%)		0/64 (0%)
Hematuria	28/50 (56%)		0/64 (0%)
Proteinuria	22/50 (44%)		0/64 (0%)
Urinary frequency	6/50 (12%)		0/64 (0%)
Urinary incontinence	4/50 (8%)		0/64 (0%)
Urinary retention	5/50 (10%)		0/64 (0%)
Urinary tract obstruction	1/50 (2%)		0/64 (0%)
Urinary tract pain	2/50 (4%)		0/64 (0%)
Reproductive system and breast disorders
Penile pain	1/50 (2%)		0/64 (0%)
Vaginal hemorrhage	1/50 (2%)		0/64 (0%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	1/50 (2%)		0/64 (0%)
Aspiration	2/50 (4%)		0/64 (0%)
Atelectasis	25/50 (50%)		0/64 (0%)
Bronchopulmonary hemorrhage	1/50 (2%)		0/64 (0%)
Cough	22/50 (44%)		0/64 (0%)
Diffuse aveolar hemorrhage	0/50 (0%)		1/64 (1.6%)
Dyspnea	28/50 (56%)		4/64 (6.3%)
Epistaxis	8/50 (16%)		4/64 (6.3%)
Hemoptysis	3/50 (6%)		0/64 (0%)
Hiccups	1/50 (2%)		0/64 (0%)
Hoarseness	1/50 (2%)		1/64 (1.6%)
Hypoxia	22/50 (44%)		4/64 (6.3%)
Nasal congestion	8/50 (16%)		0/64 (0%)
Pleural effusion	17/50 (34%)		1/64 (1.6%)
Pleuritic pain	5/50 (10%)		0/64 (0%)
Postnasal drip	5/50 (10%)		0/64 (0%)
Productive cough	6/50 (12%)		0/64 (0%)
Pulmonary edema	10/50 (20%)		0/64 (0%)
Pulmonary hypertension	1/50 (2%)		0/64 (0%)
Respiratory failure	8/50 (16%)		3/64 (4.7%)
Rhinorrhea	1/50 (2%)		0/64 (0%)
Sneezing	1/50 (2%)		0/64 (0%)
Sore throat	12/50 (24%)		0/64 (0%)
Wheezing	6/50 (12%)		1/64 (1.6%)
Skin and subcutaneous tissue disorders
Alopecia	2/50 (4%)		0/64 (0%)
Dry skin	7/50 (14%)		0/64 (0%)
Hematoma	5/50 (10%)		0/64 (0%)
Hot flashes	2/50 (4%)		0/64 (0%)
Papulopustular rash	2/50 (4%)		0/64 (0%)
Pruritus	7/50 (14%)		1/64 (1.6%)
Purpura	17/50 (34%)		0/64 (0%)
Rash acneiform	1/50 (2%)		0/64 (0%)
Rash maculo-papular	12/50 (24%)		2/64 (3.1%)
Skin nodules	1/50 (2%)		0/64 (0%)
Skin ulceration	17/50 (34%)		0/64 (0%)
Vascular disorders
Flushing	3/50 (6%)		0/64 (0%)
Hypertension	2/50 (4%)		3/64 (4.7%)
Hypotension	14/50 (28%)		7/64 (10.9%)
Superficial thrombophlebitis	1/50 (2%)		0/64 (0%)
Thromboembolic event	6/50 (12%)		2/64 (3.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.