A Study Evaluating Epoetin Alfa 40,000 IU (International Units) Every Week or 80,000 IU Every Week Compared to Placebo in Patients With Low or Intermediate-1 Risk Myelodysplastic Syndromes at Risk for Transfusion

• Sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00695396
• Collaborator: Centocor Ortho Biotech Services, L.L.C. (Industry)
• Enrollment: 25
• Arms: 4
• Duration (Months): 19

Study Details

Study Description

Brief Summary

The purpose of this study is to demonstrate that Epoetin alfa treatment reduces red blood cell transfusions in anemic patients with myelodysplastic syndromes (MDS). Myelodysplastic syndromes are a group of disorders characterized by progressive bone marrow failure and an increased risk of development of leukemia.

Condition or Disease	Intervention/Treatment	Phase
Myelodysplastic Syndromes; Anemia	Drug: Placebo; Drug: Epoetin alfa; Drug: Placebo; Drug: Epoetin alfa	Phase 3

Detailed Description

This is a randomized (patients are assigned by chance to a treatment group), double-blind (neither the patient or the physician know which treatment is being received by the patient), placebo-controlled, multicenter study of epoetin alfa in anemic patients who are diagnosed with myelodysplastic syndromes (MDS) according to protocol-specified criteria. Patients meeting entry criteria for the study will be randomly assigned to receive epoetin alfa 40,000 IU or 80,000 IU or a matching volume of placebo administered by subcutaneous (under the skin) injection once every week. Doses of study drug will be withheld, decreased, or increased on the basis of weekly hemoglobin concentrations monitored in patients and predefined dose adjustment guidelines. An Independent Data Monitoring Committee (IDMC) will periodically review study data and for the assessment of disease progression, an independent central reviewer will review bone marrow specimens and peripheral blood counts. Safety will be monitored throughout the study at predetermined intervals and as clinically indicated by physical examination, laboratory tests and evaluation of adverse events. Patients in the Treatment Phase will be randomly assigned to receive once weekly epoetin alfa subcutaneously (SC) at a dose of 40,000 IU (1 mL) or 80,000 IU (2ML) or matching volume of placebo (1 mL or 2 mL) once every week for 48 weeks. Patients may continue to receive double-blinded treatment after 48-weeks.

Study Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double Blind, Placebo Controlled, Multicenter Study Evaluating Epoetin Alfa Initiated at 40,000 IU Every Week or 80,000 IU Every Week Versus Placebo in Subjects With IPSS Low- or Intermediate-1 Risk Myelodysplastic Syndromes at Risk For Transfusion
• Study Start Date: Jun 1, 2008
• Actual Primary Completion Date: Jan 1, 2010
• Actual Study Completion Date: Jan 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 001 Epoetin alfa 40 000 IU subcutaneously once every week (1 mL dose) for 48 weeks	Drug: Epoetin alfa; 40,000 IU subcutaneously once every week (1 mL dose) for 48 weeks
Experimental: 002 Epoetin alfa 80 000 IU subcutaneously once every week (2 mL dose) for 48 weeks	Drug: Epoetin alfa; 80,000 IU subcutaneously once every week (2 mL dose) for 48 weeks
Placebo Comparator: 003 Placebo Matching volume 1 mL for 48 weeks	Drug: Placebo; Matching volume 1 mL for 48 weeks
Placebo Comparator: 004 Placebo Matching volume 2 mLfor 48 weeks	Drug: Placebo; Matching volume 2 mLfor 48 weeks

Outcome Measures

Primary Outcome Measures

1. Red Blood Cell (RBC) Transfusion [Approximately 48 weeks]

   Incidence of participants who received at least 1 Red Blood Cell (RBC) transfusion during the study (from randomization through the end of study)

Secondary Outcome Measures

1. RBC Transfusion From Day 29 Through the End of Study [Day 29 through the end of study (approximately 48 weeks)]

   incidence of participants who received at least 1 RBC transfusion from Day 29 through the end of study (approximately 48 weeks).

2. Transfusion Dependent [Approximately 48 weeks]

   Participants who were transfusion-dependent were those who received 4 or more RBC units during a consecutive 8-week period.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Diagnosis of MDS according to protocol-specified criteria via bone marrow studies performed within 12 weeks before randomization

Exclusion Criteria:

• No prior or concurrent treatment with epoetin alfa or any other approved or experimental erythropoietin stimulating agents (ESAs) within the previous 12 months before randomization

• No prior use of approved or experimental agents for the treatment of MDS or recent treatment with granulocyte colony stimulating factor (G-CSF) or granulocyte macrophage colony stimulating factor (GM-CSF) for the treatment of neutropenia

• Patients must not have secondary MDS or anemia caused by factors other than MDS (including iron deficiency, vitamin B12 or folate deficiencies, hemolysis, chronic renal failure, or gastrointestinal bleeding)

• No history (within 12 months) of deep venous thrombosis

• or history (within 6 months) of stroke, acute coronary syndrome or other arterial thrombosis

• Not currently receiving therapeutic anticoagulants or have uncontrolled hypertension

• No uncontrolled disease or dysfunction deemed clinically significant by the Investigator not attributable to MDS

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
• Centocor Ortho Biotech Services, L.L.C.

Investigators

• Study Director: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial, Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00695396
• Other Study ID Numbers: CR013651; EPOANE3018
• First Posted: Jun 11, 2008
• Last Update Posted: Oct 5, 2012
• Last Verified: Oct 1, 2012

• Keywords provided by , ,: MDS; Myelodysplastic syndromes; Anemia; Epoetin alfa; EPO
• Additional relevant MeSH terms: Preleukemia; Myelodysplastic Syndromes; Syndrome; Epoetin Alfa

Study Results

Participant Flow

Arm/Group Title	Placebo	Epoetin Alfa 40000 IU	Epoetin Alfa 80000 IU
Arm/Group Description	(1ml or 2 mL) subcutaneously once every week	(1 mL) subcutaneously once every week	(2 mL) subcutaneously once every week
Period Title: Overall Study
STARTED	8	8	9
COMPLETED	1	0	1
NOT COMPLETED	7	8	8

Baseline Characteristics

Arm/Group Title	Placebo	Epoetin Alfa 40000 IU	Epoetin Alfa 80000 IU	Total
Arm/Group Description	(1ml or 2 mL) subcutaneously once every week	(1 mL) subcutaneously once every week	(2 mL) subcutaneously once every week	Total of all reporting groups
Overall Participants	8	8	9	25
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	1 12.5%	1 12.5%	2 22.2%	4 16%
>=65 years	7 87.5%	7 87.5%	7 77.8%	21 84%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	73 (10.52)	77.3 (9.78)	67.7 (9.89)	72.4 (10.44)
Sex: Female, Male (Count of Participants)
Female	2 25%	3 37.5%	7 77.8%	12 48%
Male	6 75%	5 62.5%	2 22.2%	13 52%
Region of Enrollment (participants) [Number]
CANADA	1 12.5%	0 0%	0 0%	1 4%
ITALY	0 0%	1 12.5%	0 0%	1 4%
RUSSIA	2 25%	0 0%	4 44.4%	6 24%
USA	5 62.5%	7 87.5%	5 55.6%	17 68%

Outcome Measures

1. Primary Outcome

Title	Red Blood Cell (RBC) Transfusion
Description	Incidence of participants who received at least 1 Red Blood Cell (RBC) transfusion during the study (from randomization through the end of study)
Time Frame	Approximately 48 weeks

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population was defined as all participants randomly assigned to a treatment group, regardless of whether they received any treatment.

Arm/Group Title	Placebo	Epoetin Alfa 40000 IU	Epoetin Alfa 80000 IU
Arm/Group Description	(1ml or 2 mL) subcutaneously once every week	(1 mL) subcutaneously once every week	(2 mL) subcutaneously once every week
Measure Participants	8	8	9
Number [participants]	5 62.5%	3 37.5%	1 11.1%

2. Secondary Outcome

Title	RBC Transfusion From Day 29 Through the End of Study
Description	incidence of participants who received at least 1 RBC transfusion from Day 29 through the end of study (approximately 48 weeks).
Time Frame	Day 29 through the end of study (approximately 48 weeks)

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population was defined as all participants randomly assigned to a treatment group, regardless of whether they received any treatment.

Arm/Group Title	Placebo	Epoetin Alfa 40000 IU	Epoetin Alfa 80000 IU
Arm/Group Description	(1ml or 2 mL) subcutaneously once every week	(1 mL) subcutaneously once every week	(2 mL) subcutaneously once every week
Measure Participants	8	8	9
Number [participants]	4 50%	2 25%	1 11.1%

3. Secondary Outcome

Title	Transfusion Dependent
Description	Participants who were transfusion-dependent were those who received 4 or more RBC units during a consecutive 8-week period.
Time Frame	Approximately 48 weeks

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population.

Arm/Group Title	Placebo	Epoetin Alfa 40000 IU	Epoetin Alfa 80000 IU
Arm/Group Description	(1ml or 2 mL) subcutaneously once every week	(1 mL) subcutaneously once every week	(2 mL) subcutaneously once every week
Measure Participants	8	8	9
Number [participants]	2 25%	2 25%	1 11.1%

Adverse Events

Arm/Group Title	Placebo		Epoetin Alfa 40000 IU		Epoetin Alfa 80000 IU
Arm/Group Description	(1ml or 2 mL) subcutaneously once every week		(1 mL) subcutaneously once every week		(2 mL) subcutaneously once every week
All Cause Mortality
	Placebo		Epoetin Alfa 40000 IU		Epoetin Alfa 80000 IU
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Epoetin Alfa 40000 IU		Epoetin Alfa 80000 IU
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/8 (25%)		2/8 (25%)		4/9 (44.4%)
Blood and lymphatic system disorders
Aplasia Pure Red Cell	1/8 (12.5%)		0/8 (0%)		0/9 (0%)
Anaemia	0/8 (0%)		0/8 (0%)		1/9 (11.1%)
Splenomegaly	0/8 (0%)		0/8 (0%)		1/9 (11.1%)
Eye disorders
Vision Blurred	0/8 (0%)		1/8 (12.5%)		0/9 (0%)
Gastrointestinal disorders
Gastrointestinal Haemorrhage	0/8 (0%)		1/8 (12.5%)		0/9 (0%)
General disorders
Asthenia	0/8 (0%)		1/8 (12.5%)		0/9 (0%)
Injury, poisoning and procedural complications
Humerus Fracture	0/8 (0%)		0/8 (0%)		1/9 (11.1%)
Wrist Fracture	0/8 (0%)		0/8 (0%)		1/9 (11.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate Cancer	1/8 (12.5%)		0/8 (0%)		0/9 (0%)
Skin and subcutaneous tissue disorders
Hyperhidrosis	0/8 (0%)		1/8 (12.5%)		0/9 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Epoetin Alfa 40000 IU		Epoetin Alfa 80000 IU
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/8 (87.5%)		4/8 (50%)		6/9 (66.7%)
Blood and lymphatic system disorders
Anaemia	2/8 (25%)		0/8 (0%)		0/9 (0%)
Leukopenia	1/8 (12.5%)		0/8 (0%)		0/9 (0%)
Neutropenia	1/8 (12.5%)		1/8 (12.5%)		0/9 (0%)
Leukocytosis	0/8 (0%)		1/8 (12.5%)		0/9 (0%)
Cardiac disorders
Palpitations	0/8 (0%)		0/8 (0%)		1/9 (11.1%)
Gastrointestinal disorders
Abdominal Discomfort	1/8 (12.5%)		0/8 (0%)		0/9 (0%)
Diarrhoea	1/8 (12.5%)		1/8 (12.5%)		0/9 (0%)
Haematochezia	1/8 (12.5%)		0/8 (0%)		0/9 (0%)
Oral Pain	1/8 (12.5%)		0/8 (0%)		0/9 (0%)
Rectal Haemorrhage	1/8 (12.5%)		0/8 (0%)		0/9 (0%)
Abdominal Pain Upper	0/8 (0%)		1/8 (12.5%)		0/9 (0%)
Dyspepsia	0/8 (0%)		1/8 (12.5%)		0/9 (0%)
Nausea	0/8 (0%)		1/8 (12.5%)		2/9 (22.2%)
Vomiting	0/8 (0%)		1/8 (12.5%)		0/9 (0%)
General disorders
Fatigue	2/8 (25%)		2/8 (25%)		1/9 (11.1%)
Asthenia	1/8 (12.5%)		0/8 (0%)		2/9 (22.2%)
Hyperthermia	0/8 (0%)		0/8 (0%)		1/9 (11.1%)
Oedema Peripheral	0/8 (0%)		1/8 (12.5%)		1/9 (11.1%)
Pyrexia	0/8 (0%)		1/8 (12.5%)		0/9 (0%)
Hepatobiliary disorders
Cholelithiasis	0/8 (0%)		0/8 (0%)		1/9 (11.1%)
Immune system disorders
Hypersensitivity	0/8 (0%)		1/8 (12.5%)		0/9 (0%)
Infections and infestations
Respiratory Tract Infection	0/8 (0%)		0/8 (0%)		1/9 (11.1%)
Upper Respiratory Tract Infection	0/8 (0%)		2/8 (25%)		1/9 (11.1%)
Injury, poisoning and procedural complications
Contusion	1/8 (12.5%)		0/8 (0%)		0/9 (0%)
Investigations
Blood Urine Present	0/8 (0%)		0/8 (0%)		1/9 (11.1%)
Metabolism and nutrition disorders
Decreased Appetite	0/8 (0%)		0/8 (0%)		1/9 (11.1%)
Nervous system disorders
Dizziness	2/8 (25%)		0/8 (0%)		1/9 (11.1%)
Somnolence	1/8 (12.5%)		0/8 (0%)		0/9 (0%)
Psychiatric disorders
Insomnia	1/8 (12.5%)		1/8 (12.5%)		0/9 (0%)
Renal and urinary disorders
Pollakiuria	1/8 (12.5%)		0/8 (0%)		0/9 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	2/8 (25%)		1/8 (12.5%)		1/9 (11.1%)
Dyspnoea Exertional	0/8 (0%)		1/8 (12.5%)		0/9 (0%)
Productive Cough	0/8 (0%)		1/8 (12.5%)		0/9 (0%)
Skin and subcutaneous tissue disorders
Rash	0/8 (0%)		0/8 (0%)		1/9 (11.1%)
Vascular disorders
Hypertension	0/8 (0%)		1/8 (12.5%)		0/9 (0%)

Limitations/Caveats

Because this study was terminated prematurely due to slow enrollment, only limited data were collected. No formal statistical testing was performed. Only descriptive statistics were provided.

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.