A Survival Study in Patients With High Risk Myelodysplastic Syndromes Comparing Azacitidine Versus Conventional Care - Full Text View

Sponsored by:	Celgene Corporation
Information provided by:	Celgene Corporation
ClinicalTrials.gov Identifier:	NCT00071799

Purpose

The purpose of this study is to determine whether patients with high-risk myelodysplastic syndromes (MDS) treated with azacitidine have improved survival compared to conventional care treatments. The study will also assess the effect of treatments on response, duration of response, and transformation to acute myeloid leukemia (AML). The study will continue for 12 months following last patient enrolled.

Condition	Intervention	Phase
Myelodysplastic Syndromes	Drug: Azacitidine Other: Physician Choice	Phase III

Drug Information available for: Cytarabine Cytarabine hydrochloride Azacitidine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	A Multicenter, Randomized, Open-Label, Parallel-Group, Phase 3 Trial of Subcutaneous Azacitidine Plus Best Supportive Care Versus Conventional Care Regimens Plus Best Supportive Care for the Treatment of Myelodysplastic Syndromes (MDS)

Further study details as provided by Celgene Corporation:

Primary Outcome Measures:

Survival [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

determine the effect of azacitidine + best supportive care (BSC), relative to conventional care regimens + BSC, on hematologic status & status according to International Working Group (IWG) criteria & episodes of infections requiring IV antibiotics; [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
determine the time to relapse after CR or PR, or disease progression (according to IWG criteria), in MDS patients treated with azacitidine + BSC, as compared with patients receiving conventional care regimens + BSC; [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
to determine the time to transformation to AML, in MDS patients treated with azacitidine plus best supportive care, as compared with patients receiving conventional care regimens plus best supportive care; [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
to determine the effect of azacitidine plus best supportive care, relative to that of conventional care regimens plus best supportive care on time to AML transformation or death from any cause; [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
to determine the safety and toxicity of azacitidine plus best supportive care, relative to that of conventional care regimens plus best supportive care in MDS patients. [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]

Enrollment:	358
Study Start Date:	November 2003
Study Completion Date:	August 2007
Primary Completion Date:	July 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Azacitidine Arm: Experimental Study Drug	Drug: Azacitidine Azacitidine was injected subcutaneously (SC) at an initial dose of 75mg/m<2>/day for 7 days. The 7-day dosing was repeated every 28 days with dose adjustment based on predefined hematology and renal laboratory results. Number of cycles: Azacitidine treatment was to be continued until the end of the study unless treatment was discontinued due to unacceptable toxicity, relapse after complete or partial response, transformation to AML or disease progression.
Conventional Care: Active Comparator Physician choice of low dose cytarabine, standard chemotherapy or best supportive care consisting of blood products, growth factors, antibiotics	Other: Physician Choice Physician Choice of low dose cytarabine, standard chemotherapy, or best supportive care consisting of blood products, growth factors, antibiotics.

Arms

Assigned Interventions

Azacitidine Arm: Experimental

Study Drug

Drug: Azacitidine

Azacitidine was injected subcutaneously (SC) at an initial dose of 75mg/m<2>/day for 7 days. The 7-day dosing was repeated every 28 days with dose adjustment based on predefined hematology and renal laboratory results. Number of cycles: Azacitidine treatment was to be continued until the end of the study unless treatment was discontinued due to unacceptable toxicity, relapse after complete or partial response, transformation to AML or disease progression.

Conventional Care: Active Comparator

Physician choice of low dose cytarabine, standard chemotherapy or best supportive care consisting of blood products, growth factors, antibiotics

Other: Physician Choice

Physician Choice of low dose cytarabine, standard chemotherapy, or best supportive care consisting of blood products, growth factors, antibiotics.

Detailed Description:

Comparison/Control Interventions: Best supportive care, or low dose cytarabine plus best supportive care.

Duration of Intervention: Patients will be treated until death, withdrawal, or conclusion of the study.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Have a diagnosis of refractory anemia with excess blasts or refractory anemia with excess blasts in transformation according to the French-American-British classification system for MDS and a relatively high risk of AML transformation, with an International Prognostic Scoring System score of INT-2 or High.
Be 18 years of age or older
Have a life expectancy of at least 3 months
Be unlikely to proceed to bone marrow or stem cell transplantation therapy following remission
Have serum bilirubin levels less than or equal to 1.5 times the upper limit of normal range for the laboratory
Have serum glutamic-oxaloacetic transaminase (aspartate aminotransferase) or serum glutamic-pyruvic transaminase (alanine aminotransferase) levels less than or equal to 2 times the upper limit of normal (unless these are considered to be related to transfusion-induced secondary hemosiderosis)
Have serum creatinine levels less than or equal to 1.5 times the upper limit of normal

Exclusion Criteria:

Secondary MDS
Prior treatment with azacitidine;
Prior history of AML;
Malignant disease diagnosed within prior 12 months;
Metastatic disease;
Hepatic tumors;
Radiation, chemotherapy, cytotoxic therapy for non-MDS conditions within prior 12 months;
Prior transplantation or cytotoxic therapy to treat MDS;
Serious medical illness likely to limit survival to 12 months or less;
Treatment with erythropoietin or myeloid growth factors during prior 21 days or androgenic hormones during prior 13 days;
Active HIV, viral hepatitis type B or C;
Treatment with investigational drugs during prior 30 days.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00071799

Show 105 Study Locations

Sponsors and Collaborators

Celgene Corporation

Investigators

Study Director:

CL Beach

Celgene Corporation

More Information

Responsible Party:	Pharmion Corporation ( Linda Zimmerman )
Study ID Numbers:	AZA PH GL 2003 CL 001
Study First Received:	October 31, 2003
Last Updated:	September 22, 2008
ClinicalTrials.gov Identifier:	NCT00071799
Health Authority:	United States: Food and Drug Administration

Study placed in the following topic categories:

Myelodysplastic syndromes
Preleukemia
Precancerous Conditions
Hematologic Diseases
Myelodysplasia

Myelodysplastic Syndromes
Azacitidine
Bone Marrow Diseases
Cytarabine

Additional relevant MeSH terms:

Antimetabolites
Neoplasms
Antimetabolites, Antineoplastic
Pathologic Processes
Disease
Molecular Mechanisms of Pharmacological Action

Antineoplastic Agents
Therapeutic Uses
Syndrome
Enzyme Inhibitors
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009