Azacitidine and Erythropoietin Versus Azacitidine Alone for Patients With Low-Risk Myelodysplastic Syndromes

• Sponsor: Larry Cripe, MD (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00379912
• Collaborator: Celgene Corporation (Industry), Ortho Biotech Clinical Affairs, L.L.C. (Industry), Walther Cancer Institute (Other)
• Enrollment: 15
• Locations: 9
• Arms: 2
• Duration (Months): 27
• Patients Per Site: 1.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This trial is designed to explore a modified dose and schedule of azacitidine in order to more effectively address the needs of patients with low-risk myelodysplastic syndromes (MDS), i.e., to alter the natural history of the disease without excessive toxicity or burden. The administration of erythropoietin is designed to influence the differentiation of primitive hematopoietic cells in which azacitidine has reversed the abnormal phenotype to red blood cells for patients in whom inadequate production of red blood cells is the major clinical issue.

Condition or Disease	Intervention/Treatment	Phase
Myelodysplastic Syndromes	Drug: Azacitidine; Drug: Erythropoietin; Drug: Azacitidine (Monotherapy)	Phase 2

Detailed Description

OUTLINE: This is an open label, multi-center, randomized study.

Eligible patients will be randomized to one of two treatment arms:

Arm A (Azacitidine + Erythropoietin)

• Azacitidine Treatment 50 mg/m2 subcutaneously every other day (three times a week) for two consecutive weeks every four weeks. A cycle of therapy is defined as two consecutive weeks of subcutaneous azacitidine administered every other day three times a week (e.g. Monday - Wednesday - Friday) and the time to resolution of any treatment associated toxicity.

• Erythropoietin Treatment Patients who are randomized to Arm A will receive a dose of 60,000IU as a single subcutaneous injection weekly without interruption while enrolled on protocol therapy. The dose should be administered to coincide with the first day of each cycle.

• Protocol therapy may be administered for up to six cycles of therapy.

Arm B (Azacitidine Alone)

• Azacitidine Treatment 50 mg/m2 subcutaneously every other day (three times a week) for two consecutive weeks every four weeks. A cycle of therapy is defined as two consecutive weeks of subcutaneous azacitidine administered every other day three times a week (e.g. Monday - Wednesday - Friday) and the time to resolution of any treatment associated toxicity.

• Protocol therapy may be administered for up to six cycles of therapy.

ECOG performance status 0 to 2

Hematopoietic:

To be eligible for randomization, subjects must have documentation of at least 1 of the following:

• A transfusion dependent anemia (defined by a history of two or more episodes of transfusion within a period of 8 weeks).

• An untransfused hemoglobin < 10 gm/dl measured on at least two occasions more than 7 days apart in the month prior to randomization.

Patients must also meet 1 of the following criteria:

• Has not received prior erythropoietin and has a serum erythropoietin level > 200 IU/L within 14 days of randomization.

• Has received prior erythropoietin without clinical benefit in the judgment of the treating physician.

• Adequate iron status defined as serum ferritin > 20 ng/ml and transferrin saturation of

30% within 90 days prior to randomization.

• Symptoms attributed to the anemia with hemoglobin < 11 g/dL.

• Folate and Vitamin B12 levels within normal limits within 90 days prior to randomization.

Hepatic:

• SGOT (ALT) level < 2 x ULN within 14 days prior to randomization.

• SGPT (AST) level < 2 x ULN within 14 days prior to randomization.

• Serum total bilirubin level < 2 x ULN within 14 days prior to randomization.

Renal:

• Serum creatine < 1.5 x the upper limit of normal (ULN) within 14 days prior to randomization.

Cardiovascular:

• No uncontrolled hypertension (defined as a systolic pressure > 160 mmHg and/or a diastolic pressure > 110 mmHg).

• No history of (within 12 months) deep venous thrombosis (DVT), pulmonary embolism (PE), or other venous thrombosis. Prior superficial thrombophlebitis is not an exclusion criterion.

• No history of (within 6 months) cerebrovascular accident ([CVA] includes ischemic, embolic, and hemorrhagic), transient ischemic attack (TIA), myocardial ischemia (includes Unstable Angina, Q wave Myocardial Infarction [QwMI], and non-Q wave Myocardial Infarction [NQMI]), or other arterial thrombosis.

Study Design

• Study Type: Interventional
• Actual Enrollment: 15 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Randomized Trial With A Modified Dose & Schedule of Subcutaneously Administered Azacitidine & Erythropoietin v Azacitidine Alone in Patients With Low-Risk Myelodysplastic Syndromes (Less Than 11% Marrow & Peripheral Blood Blasts)
• Study Start Date: Sep 1, 2006
• Actual Primary Completion Date: Dec 1, 2008
• Actual Study Completion Date: Dec 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Investigational Arm A Azacitidine + Erythropoietin	Drug: Azacitidine; Azacitidine 50 mg/m2 subcutaneously qod for two consecutive weeks every four weeks.; Other Names: Vidaza ; Drug: Erythropoietin; Erythropoietin 60,000IU subcutaneous injection weekly while on protocol therapy; Other Names: EPO
Experimental: Investigational Arm B Azacitidine	Drug: Azacitidine (Monotherapy); Azacitidine 50 mg/m2 subcutaneously qod for two consecutive weeks every four weeks.; Other Names: Vidaza

Outcome Measures

Primary Outcome Measures

1. Overall Response After Cycle 3 [3 months]

   Overall response for participants who have completed at least three cycles of protocol-specified therapy according to the International Working Group to Standardize Response Criteria for Myelodysplastic Syndromes criteria for Erythroid Response (HI-E) Major response: For patients with pretreatment hemoglobin less than 11 g/dL, greater than 2 g/dL increase in hemoglobin; for RBC transfusion-dependent patients, transfusion independence. Minor response: For patients with pretreatment hemoglobin less than 11 g/dL, 1 to 2 g/dL increase in hemoglobin; for RBC transfusion-dependent patients, 50% decrease in transfusion requirements.

2. Overall Response Rate After Six Cycles [6 months]

   Overall response rate for participants who have completed at least six cycles of protocol-specified therapy according to the International Working Group to Standardize Response Criteria for Myelodysplastic Syndromes criteria for Erythroid Response (HI-E) Major response: For patients with pretreatment hemoglobin less than 11 g/dL, greater than 2 g/dL increase in hemoglobin; for RBC transfusion-dependent patients, transfusion independence. Minor response: For patients with pretreatment hemoglobin less than 11 g/dL, 1 to 2 g/dL increase in hemoglobin; for RBC transfusion-dependent patients, 50% decrease in transfusion requirements.

Secondary Outcome Measures

1. Safety Profile of the Modified Dose/Schedule of Azacitidine and Erythropoietin or a Modified Dose of Azacitidine Alone [24 months]

   Full adverse event information is submitted in the record below. A summary of the Significant Toxicities Rate (clinically significant myelosuppression (CTCAE Grade 3 or 4 neutropenia or thrombocytopenia)) over all patients receiving at least 1 dose of study medication at the time of interim analysis is reported in this outcome measure.

2. Duration of Significant Responses [24 months]

   Data for this outcome measure was not collected or analyzed due to the termination of the study.

3. Quality of Life [24 months]

   Data for this outcome measure was not collected or analyzed due to the termination of the study

4. Analysis of CD34, CD71, CD36 Cells in Aspirated Bone Marrow for Both Responders and Non-responders at Baseline and After Three and Six Cycles [6 months]

5. Percent Apoptosis in 34+36+71+ Cells at Baseline, Three Cycles and Six Cycles [Six months]

6. BclXL Expression [Six months]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• A bone marrow (BM) aspirate and biopsy that demonstrates MDS with less than 11% blasts.

• Conventional metaphase cytogenetics done within 90 days prior to registration for screening.

• Central pathology review, correlative submission and confirmation of diagnosis is required prior to initiation of therapy (see Study Procedure Manual for details of submission). The FAB and WHO classification of MDS and the IPSS score will be determined at time of central pathology review.

• Correlative marrow aspirate obtained.

To be eligible for randomization, subjects must have documentation of at least 1 of the following:

• A transfusion dependent anemia (defined by a history of two or more episodes of transfusion within a period of 8 weeks).

• An untransfused hemoglobin < 10 gm/dl measured on at least two occasions more than 7 days apart in the month prior to randomization.

Patients must also meet 1 of the following criteria:

• Has not received prior erythropoietin and has a serum erythropoietin level > 200 IU/L within 14 days of randomization.

• Has received prior erythropoietin without clinical benefit in the judgment of the treating physician.

• Adequate iron status defined as serum ferritin > 20 ng/ml and transferrin saturation of > 30% within 90 days prior to randomization.

• Symptoms attributed to the anemia with hemoglobin < 11 g/dL.

• Folate and Vitamin B12 levels within normal limits within 90 days prior to randomization.

• Life expectancy > 6 months as judged by the treating investigator.

Exclusion Criteria:

• No known history of intolerance to erythropoietic agents.

• No prior intensive cytotoxic chemotherapy for a myeloid malignancy including MDS.

• Patients with a history of a non-myeloid malignancy with secondary MDS are eligible for study enrollment provided, in the opinion of the treating investigator and the study chair, the anticipated behavior of the non-myeloid malignancy will not interfere with study participation and evaluation of outcome.

• No known or suspected hypersensitivity to azacitidine or mannitol.

• No hepatic tumors.

• No uncontrolled hypertension (defined as a systolic pressure > 160 mmHg and/or a diastolic pressure > 110 mmHg).

• No known hypersensitivity to mammalian cell-derived products or human albumin.

• No history of (within 12 months) deep venous thrombosis (DVT), pulmonary embolism (PE), or other venous thrombosis. Prior superficial thrombophlebitis is not an exclusion criterion.

• No history of (within 6 months) cerebrovascular accident ([CVA] includes ischemic, embolic and hemorrhagic), transient ischemic attack (TIA), myocardial ischemia (includes Unstable Angina, Q wave Myocardial Infarction [QwMI] and non-Q wave Myocardial Infarction [NQMI], or other arterial thrombosis.

• Females of childbearing potential and males must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) while on treatment and for a 4-week period thereafter.

• Females with childbearing potential must have a negative pregnancy test within 7 days prior to being randomized. Patients are considered not of child bearing potential if they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medical & Surgical Specialists, LLC	Galesburg	Illinois	United States	61401
2	Indiana University Cancer Center	Indianapolis	Indiana	United States	46202
3	Quality Cancer Center (MCGOP)	Indianapolis	Indiana	United States	46202
4	Arnett Cancer Care	Lafayette	Indiana	United States	47904
5	Horizon Oncology Center	Lafayette	Indiana	United States	47905
6	Medical Consultants, P.C.	Muncie	Indiana	United States	47303
7	Northern Indiana Cancer Research Consortium	South Bend	Indiana	United States	46601
8	Center for Hematology-Oncology of S Michigan	Jackson	Michigan	United States	49201
9	Methodist Cancer Center	Omaha	Nebraska	United States	68114

Sponsors and Collaborators

• Larry Cripe, MD
• Celgene Corporation
• Ortho Biotech Clinical Affairs, L.L.C.
• Walther Cancer Institute

Investigators

• Study Chair: Larry Cripe, M.D., Hoosier Oncology Group, LLC

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Hoosier Oncology Group Home Page

Publications

None provided.

• Responsible Party: Larry Cripe, MD, Sponsor-Investigator, Hoosier Cancer Research Network
• ClinicalTrials.gov Identifier: NCT00379912
• Other Study ID Numbers: HOG MDS04-85
• First Posted: Sep 25, 2006
• Last Update Posted: Feb 14, 2018
• Last Verified: Jan 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Preleukemia; Myelodysplastic Syndromes; Syndrome; Azacitidine; Epoetin Alfa

Study Results

Participant Flow

Arm/Group Title	Arm A Azacitidine + Erythropoietin	Arm B Azacitidine
Arm/Group Description	Azacitidine + Erythropoietin Azacitidine: Azacitidine 50 mg/m2 subcutaneously qod for two consecutive weeks every four weeks. Erythropoietin: Erythropoietin 60,000IU subcutaneous injection weekly while on protocol therapy	Azacitidine Azacitidine (Monotherapy): Azacitidine 50 mg/m2 subcutaneously qod for two consecutive weeks every four weeks.
Period Title: Overall Study
STARTED	7	8
COMPLETED	6	8
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Arm A Azacitidine + Erythropoietin	Arm B Azacitidine	Total
Arm/Group Description	Azacitidine + Erythropoietin Azacitidine: Azacitidine 50 mg/m2 subcutaneously qod for two consecutive weeks every four weeks. Erythropoietin: Erythropoietin 60,000IU subcutaneous injection weekly while on protocol therapy	Azacitidine Azacitidine (Monotherapy): Azacitidine 50 mg/m2 subcutaneously qod for two consecutive weeks every four weeks.	Total of all reporting groups
Overall Participants	7	8	15
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	69	67.50	69
Sex: Female, Male (Count of Participants)
Female	1 14.3%	1 12.5%	2 13.3%
Male	6 85.7%	7 87.5%	13 86.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	7 100%	8 100%	15 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	7 100%	8 100%	15 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	7 100%	8 100%	15 100%

Outcome Measures

1. Primary Outcome

Title	Overall Response After Cycle 3
Description	Overall response for participants who have completed at least three cycles of protocol-specified therapy according to the International Working Group to Standardize Response Criteria for Myelodysplastic Syndromes criteria for Erythroid Response (HI-E) Major response: For patients with pretreatment hemoglobin less than 11 g/dL, greater than 2 g/dL increase in hemoglobin; for RBC transfusion-dependent patients, transfusion independence. Minor response: For patients with pretreatment hemoglobin less than 11 g/dL, 1 to 2 g/dL increase in hemoglobin; for RBC transfusion-dependent patients, 50% decrease in transfusion requirements.
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

Participants completing at least three cycles at the time of analysis.

Arm/Group Title	Arm A Azacitidine + Erythropoietin	Arm B Azacitidine
Arm/Group Description	Azacitidine + Erythropoietin Azacitidine: Azacitidine 50 mg/m2 subcutaneously qod for two consecutive weeks every four weeks. Erythropoietin: Erythropoietin 60,000IU subcutaneous injection weekly while on protocol therapy	Azacitidine Azacitidine (Monotherapy): Azacitidine 50 mg/m2 subcutaneously qod for two consecutive weeks every four weeks.
Measure Participants	6	6
Number (90% Confidence Interval) [percentage of participants responding]	50 714.3%	33.3 416.3%

2. Primary Outcome

Title	Overall Response Rate After Six Cycles
Description	Overall response rate for participants who have completed at least six cycles of protocol-specified therapy according to the International Working Group to Standardize Response Criteria for Myelodysplastic Syndromes criteria for Erythroid Response (HI-E) Major response: For patients with pretreatment hemoglobin less than 11 g/dL, greater than 2 g/dL increase in hemoglobin; for RBC transfusion-dependent patients, transfusion independence. Minor response: For patients with pretreatment hemoglobin less than 11 g/dL, 1 to 2 g/dL increase in hemoglobin; for RBC transfusion-dependent patients, 50% decrease in transfusion requirements.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Participants completing at least six cycles at the time of analysis.

Arm/Group Title	Arm B Azacitidine	Arm A Azacitidine + Erythropoietin
Arm/Group Description	Azacitidine Azacitidine (Monotherapy): Azacitidine 50 mg/m2 subcutaneously qod for two consecutive weeks every four weeks.	Azacitidine + Erythropoietin Azacitidine: Azacitidine 50 mg/m2 subcutaneously qod for two consecutive weeks every four weeks. Erythropoietin: Erythropoietin 60,000IU subcutaneous injection weekly while on protocol therapy
Measure Participants	6	6
Number (90% Confidence Interval) [percentage of participants responding]	33.3 475.7%	33.3 416.3%

3. Secondary Outcome

Title	Safety Profile of the Modified Dose/Schedule of Azacitidine and Erythropoietin or a Modified Dose of Azacitidine Alone
Description	Full adverse event information is submitted in the record below. A summary of the Significant Toxicities Rate (clinically significant myelosuppression (CTCAE Grade 3 or 4 neutropenia or thrombocytopenia)) over all patients receiving at least 1 dose of study medication at the time of interim analysis is reported in this outcome measure.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

All patients receiving at least 1 dose of study medication at the time of interim analysis.

Arm/Group Title	Arm A Azacitidine + Erythropoietin	Arm B Azacitidine
Arm/Group Description	Azacitidine + Erythropoietin Azacitidine: Azacitidine 50 mg/m2 subcutaneously qod for two consecutive weeks every four weeks. Erythropoietin: Erythropoietin 60,000IU subcutaneous injection weekly while on protocol therapy	Azacitidine Azacitidine (Monotherapy): Azacitidine 50 mg/m2 subcutaneously qod for two consecutive weeks every four weeks.
Measure Participants	6	6
Number (90% Confidence Interval) [percentage of participants]	66.7 952.9%	66.4 830%

4. Secondary Outcome

Title	Duration of Significant Responses
Description	Data for this outcome measure was not collected or analyzed due to the termination of the study.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A Azacitidine + Erythropoietin	Arm B Azacitidine
Arm/Group Description	Azacitidine + Erythropoietin Azacitidine: Azacitidine 50 mg/m2 subcutaneously qod for two consecutive weeks every four weeks. Erythropoietin: Erythropoietin 60,000IU subcutaneous injection weekly while on protocol therapy	Azacitidine Azacitidine (Monotherapy): Azacitidine 50 mg/m2 subcutaneously qod for two consecutive weeks every four weeks.
Measure Participants	0	0

5. Secondary Outcome

Title	Quality of Life
Description	Data for this outcome measure was not collected or analyzed due to the termination of the study
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Investigational Arm A	Investigational Arm B
Arm/Group Description	Azacitidine + Erythropoietin Azacitidine: Azacitidine 50 mg/m2 subcutaneously qod for two consecutive weeks every four weeks. Erythropoietin: Erythropoietin 60,000IU subcutaneous injection weekly while on protocol therapy	Azacitidine Azacitidine (Monotherapy): Azacitidine 50 mg/m2 subcutaneously qod for two consecutive weeks every four weeks.
Measure Participants	0	0

6. Secondary Outcome

Title	Analysis of CD34, CD71, CD36 Cells in Aspirated Bone Marrow for Both Responders and Non-responders at Baseline and After Three and Six Cycles
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Analysis of CD34, CD71, and CD36 cells was undertaken irrespective of arm assignment.

Arm/Group Title	Responders	Non-Responders
Arm/Group Description	Responders	Non-Responders
Measure Participants	6	8
CD34 Baseline	.86 (.56)	.49 (.38)
CD34 After Three Cycles	.93 (.78)	.58 (.28)
CD34 After Six Cycles	1.15 (.59)	.52 (.39)
CD71 at Baseline	18.32 (5.30)	7.23 (3.32)
CD71 After Three Cycles	27.31 (14.33)	10.13 (5.85)
CD71 After Six Cycles	35.45 (16.50)	9.69 (7.36)
CD36 at Baseline	11.69 (2.76)	5.12 (1.94)
CD36 after Three Cycles	14.33 (6.64)	6.08 (4.27)
CD36 after Six Cycles	21.35 (9.23)	3.57 (1.01)

7. Secondary Outcome

Title	Percent Apoptosis in 34+36+71+ Cells at Baseline, Three Cycles and Six Cycles
Time Frame	Six months

Outcome Measure Data

Analysis Population Description

Analysis of percent apoptosis was undertaken irrespective of arm assignment and categorized between responsers and non-responders

Arm/Group Title	Responders	Non-Responders
Arm/Group Description	Responders	Non-Responders
Measure Participants	6	8
% apoptosis at baseline	17.04 (6.04)	31.19 (12.03)
% apoptosis after three cycles	24.70 (9.01)	63.43 (7.72)
% apoptosis after six cycles	42.58 (11.41)	38.10 (4.84)

8. Secondary Outcome

Title	BclXL Expression
Time Frame	Six months

Outcome Measure Data

Analysis Population Description

Analysis of BclXL expression was undertaken irrespective of arm assignment and categorized between responsers and non-responders

Arm/Group Title	Responders	Non-Responders
Arm/Group Description	Responders	Non-Responders
Measure Participants	6	8
BclXL Expression at baseline	1.0 (0.00)	1.00 (0)
BclXL Expression after three cycles	1.50 (0.32)	.77 (.15)
BclXL Expression after six cycles	3.89 (.99)	1.21 (.37)

Adverse Events

Time Frame	The duration of study participation, up to two years
Arm/Group Title	Arm A Azacitidine + Erythropoietin		Arm B Azacitidine
Arm/Group Description	Azacitidine + Erythropoietin Azacitidine: Azacitidine 50 mg/m2 subcutaneously qod for two consecutive weeks every four weeks. Erythropoietin: Erythropoietin 60,000IU subcutaneous injection weekly while on protocol therapy		Azacitidine Azacitidine (Monotherapy): Azacitidine 50 mg/m2 subcutaneously qod for two consecutive weeks every four weeks.
All Cause Mortality
	Arm A Azacitidine + Erythropoietin		Arm B Azacitidine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm A Azacitidine + Erythropoietin		Arm B Azacitidine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/7 (57.1%)		2/8 (25%)
Cardiac disorders
SUPRAVENTRICULAR AND NODAL ARRHYTHMIA / ATRIAL FIBRILLATION	1/7 (14.3%)	1	0/8 (0%)	0
Gastrointestinal disorders
ENTERITIS (INFLAMMATION OF THE SMALL BOWEL)	1/7 (14.3%)	1	0/8 (0%)	0
HEMORRHAGE, GI / UPPER GI NOS	0/7 (0%)	0	1/8 (12.5%)	1
General disorders
FEVER (IN THE ABSENCE OF NEUTROPENIA, WHERE NEUTROPENIA IS DEFINED AS ANC <1.0 X 10E9/L)	0/7 (0%)	0	1/8 (12.5%)	1
TUMOR LYSIS SYNDROME	1/7 (14.3%)	1	0/8 (0%)	0
Infections and infestations
INFECTION WITH NORMAL ANC OR GRADE 1 OR 2 NEUTROPHILS / BLADDER (URINARY)	0/7 (0%)	0	1/8 (12.5%)	1
Respiratory, thoracic and mediastinal disorders
PLEURAL EFFUSION (NON-MALIGNANT)	1/7 (14.3%)	1	0/8 (0%)	0
Other (Not Including Serious) Adverse Events
	Arm A Azacitidine + Erythropoietin		Arm B Azacitidine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/7 (100%)		7/8 (87.5%)
Blood and lymphatic system disorders
EDEMA: LIMB	2/7 (28.6%)	2	0/8 (0%)	0
HEMATOMA	0/7 (0%)	0	1/8 (12.5%)	1
HEMOGLOBIN	4/7 (57.1%)	15	7/8 (87.5%)	19
IRON OVERLOAD	0/7 (0%)	0	1/8 (12.5%)	1
LEUKOCYTES (TOTAL WBC)	1/7 (14.3%)	5	0/8 (0%)	0
NEUTROPHILS/GRANULOCYTES (ANC/AGC)	5/7 (71.4%)	15	5/8 (62.5%)	15
PLATELETS	3/7 (42.9%)	12	4/8 (50%)	24
Cardiac disorders
CARDIAC ARRHYTHMIA	1/7 (14.3%)	1	0/8 (0%)	0
HYPERTENSION	0/7 (0%)	0	1/8 (12.5%)	1
HYPOTENSION	0/7 (0%)	0	1/8 (12.5%)	1
Ear and labyrinth disorders
AUDITORY/EAR	1/7 (14.3%)	1	0/8 (0%)	0
PAIN / MIDDLE EAR	0/7 (0%)	0	1/8 (12.5%)	1
Gastrointestinal disorders
ANOREXIA	1/7 (14.3%)	1	2/8 (25%)	2
CONSTIPATION	1/7 (14.3%)	1	4/8 (50%)	5
DIARRHEA	1/7 (14.3%)	1	1/8 (12.5%)	1
ESOPHAGITIS	0/7 (0%)	0	1/8 (12.5%)	1
HEMORRHOIDS	0/7 (0%)	0	1/8 (12.5%)	1
MUCOSITIS/STOMATITIS (FUNCTIONAL/SYMPTOMATIC) / ORAL CAVITY	0/7 (0%)	0	1/8 (12.5%)	1
NAUSEA	0/7 (0%)	0	1/8 (12.5%)	1
PAIN / ABDOMEN NOS	1/7 (14.3%)	3	1/8 (12.5%)	1
VOMITING	0/7 (0%)	0	1/8 (12.5%)	1
General disorders
FATIGUE (ASTHENIA, LETHARGY, MALAISE)	4/7 (57.1%)	10	2/8 (25%)	4
FEVER (IN THE ABSENCE OF NEUTROPENIA, WHERE NEUTROPENIA IS DEFINED AS ANC <1.0 X 10E9/L)	0/7 (0%)	0	1/8 (12.5%)	2
INSOMNIA	0/7 (0%)	0	1/8 (12.5%)	1
PAIN / NECK	1/7 (14.3%)	1	0/8 (0%)	0
PAIN	0/7 (0%)	0	1/8 (12.5%)	1
RIGORS/CHILLS	0/7 (0%)	0	1/8 (12.5%)	2
SWEATING (DIAPHORESIS)	1/7 (14.3%)	1	0/8 (0%)	0
WEIGHT LOSS	1/7 (14.3%)	1	0/8 (0%)	0
Hepatobiliary disorders
PAIN / GALLBLADDER	1/7 (14.3%)	1	0/8 (0%)	0
Immune system disorders
ALLERGIC RHINITIS (INCLUDING SNEEZING, NASAL STUFFINESS, POSTNASAL DRIP)	0/7 (0%)	0	2/8 (25%)	2
Infections and infestations
INFECTION WITH GRADE 3 OR 4 NEUTROPHILS (ANC <1.0 X 10E9/L) / ABDOMEN NOS	1/7 (14.3%)	1	0/8 (0%)	0
INFECTION WITH GRADE 3 OR 4 NEUTROPHILS (ANC <1.0 X 10E9/L) / MIDDLE EAR (OTITIS MEDIA)	0/7 (0%)	0	1/8 (12.5%)	1
INFECTION WITH GRADE 3 OR 4 NEUTROPHILS (ANC <1.0 X 10E9/L) / URINARY TRACT NOS	0/7 (0%)	0	1/8 (12.5%)	1
INFECTION WITH NORMAL ANC OR GRADE 1 OR 2 NEUTROPHILS / LUNG (PNEUMONIA)	0/7 (0%)	0	1/8 (12.5%)	1
INFECTION WITH NORMAL ANC OR GRADE 1 OR 2 NEUTROPHILS / URINARY TRACT NOS	0/7 (0%)	0	1/8 (12.5%)	1
Investigations
URIC ACID, SERUM-HIGH (HYPERURICEMIA)	1/7 (14.3%)	2	0/8 (0%)	0
Musculoskeletal and connective tissue disorders
ARTHRITIS (NON-SEPTIC)	0/7 (0%)	0	1/8 (12.5%)	1
PAIN / BONE	0/7 (0%)	0	1/8 (12.5%)	1
PAIN / EXTREMITY-LIMB	1/7 (14.3%)	2	0/8 (0%)	0
Nervous system disorders
DIZZINESS	1/7 (14.3%)	1	1/8 (12.5%)	1
Psychiatric disorders
MOOD ALTERATION / ANXIETY	0/7 (0%)	0	1/8 (12.5%)	1
Respiratory, thoracic and mediastinal disorders
COUGH	1/7 (14.3%)	1	1/8 (12.5%)	1
DYSPNEA (SHORTNESS OF BREATH)	4/7 (57.1%)	5	2/8 (25%)	2
Skin and subcutaneous tissue disorders
BRUISING (IN ABSENCE OF GRADE 3 OR 4 THROMBOCYTOPENIA)	1/7 (14.3%)	1	0/8 (0%)	0
HAIR LOSS/ALOPECIA (SCALP OR BODY)	0/7 (0%)	0	1/8 (12.5%)	1
HYPERPIGMENTATION	0/7 (0%)	0	1/8 (12.5%)	2
INJECTION SITE REACTION/EXTRAVASATION CHANGES	1/7 (14.3%)	1	1/8 (12.5%)	1

Limitations/Caveats

Results of interim analysis led to early closure of the study.

More Information

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.