Clinical trial NCT00102687: Alternative Dosing Regimens of Subcutaneous Azacitidine for Myelodysplastic Syndromes
Official title: A Multicenter, Randomized, Open-Label Study Comparing Three Alternative Dosing Regimens of Subcutaneous Azacitidine Plus Best Supportive Care for the Treatment of Myelodysplastic Syndromes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Myelodysplastic Syndromes
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2005-02-01
Enrollment: 151
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine if azacitidine, combined with Best Supportive Care (BSC), is effective in treating myelodysplastic syndromes (MDS) when given according to a different doses and dosing schedules.

Detailed description: Comparison/Control Interventions: The comparison is azacitidine at different doses and schedules.

Duration of Intervention: Treatment lasted for a maximum of 18 cycles, which is up to 24 months.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of refractory anemia, refractory anemia with ringed sideroblasts and at least one of the following: a)Anemia with hemoglobin \<110g/L and requires at least 1 unit packed red blood cell transfusions every 28 days; b)Thrombocytopenia with platelet counts \<100 x 10\^9/L; or c)Neutropenia with absolute neutrophil count \<1.5 x 10\^9/L.
* OR, Refractory anemia with excess blasts or refractory anemia with excess blast in transformation, according to the French-American-British classification system for MDS.
* At least 18 years of age.
* Have a life expectancy of \>7 months.
* 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 the normal (ULN) 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 x ULN.
* Have serum creatinine levels less than or equal to 1.5 x ULN.

Exclusion Criteria:

* Secondary MDS.
* Prior treatment with azacitidine.
* Any prior history of Acute Myeloid Leukemia (AML).
* Malignant or metastatic disease within the previous 12 months.
* Uncorrected red cell folate deficiency or vitamin B12 deficiency.
* Hepatic tumors.
* Radiation, chemotherapy, or cytotoxic therapy for non-MDS conditions in the previous 12 months.
* Known or suspected hypersensitivity to azacitidine or mannitol.
* Prior transplantation or cytotoxic therapy to treat MDS. Prior use of Revlimid and Thalomid allowed after 30 day washout.
* Serious medical illness likely to limit survival to less than or equal to 7 months.
* Treatment with androgenic hormones during the previous 14 days
* Active viral infection with known human immunodeficiency virus or vial hepatitis Type B or C.
* Treatment with other investigational drugs with the previous 30 days.

Primary outcomes:
measure: Number of Participants In Best Hematological Response Categories as Determined by the Investigator Using International Working Group 2000 (IWG 2000) Criteria For Myelodysplastic Syndromes (MDS) During the Initial Study Period.
timeFrame: Day 1 (randomization) to 6 months
measure: Number of Participants With Best Hematological Improvement Derived Using International Working Group 2000 (IWG 2000) Criteria for MDS During the Initial Study Period.
timeFrame: Day 1 (randomization) to 6 months
measure: Number of Participants With Overall Best Hematologic Response and Hematologic Improvement Based on IWG 2000 Criteria For MDS During the Initial Study Period
timeFrame: Day 1 (randomization) to 6 months
measure: Number of Participants Who Improved or Maintained The Hematologic Response From the Initial Study Period (Based on IWG 2000 Criteria For MDS) During the Maintenance Period
timeFrame: 24 months
Secondary outcomes:
measure: Baseline Hemoglobin Values
timeFrame: Day 1 (randomization)
measure: Change From Baseline in Hemoglobin at End of Initial Study Period (6 Months)
timeFrame: 6 months
measure: Change From Baseline in Hemoglobin at the End of the Maintenance Study Period
timeFrame: 24 months
measure: Baseline Platelet Values
timeFrame: Day 1 (randomization)
measure: Change From Baseline in Platelets at the End of Initial Study Period (6 Months)
timeFrame: 6 months
measure: Change From Baseline in Platelets at the End of the Maintenance Study Period (Month 24)
timeFrame: 24 months
measure: Baseline Absolute Neutrophil Count (ANC) Values
timeFrame: Day 1 (randomization)
measure: Change From Baseline in Absolute Neutrophil Count (ANC) at the End of Initial Study Period (6 Months)
timeFrame: 6 months
measure: Change From Baseline in Absolute Neutrophil Count (ANC) at the End of the Maintenance Study Period (Month 24)
timeFrame: 24 months
measure: Red Blood Cell (RBC) Transfusion Status at Baseline and End of Initial Study Period (6 Months)
timeFrame: 6 months
measure: Platelet Transfusion Status at Baseline and End of Initial Study Period (6 Months)
timeFrame: 6 months
measure: Red Blood Cell (RBC) Transfusion Status at Baseline and End of Maintenance Study Period (24 Months)
timeFrame: 24 months
measure: Platelet Transfusion Status at Baseline and End of Maintenance Study Period (24 Months)
timeFrame: 24 months
measure: Change From Baseline in the Number of Infections Requiring Treatment With IV Antibiotics Per Treatment Cycle (28 Days) for the Initial Study Period
timeFrame: 6 months
measure: Change From Baseline in the Number of Infections Requiring Treatment With IV Antibiotics Per Treatment Cycle (28 Days) for the Maintenance Study Period
timeFrame: 24 months
Other outcomes:
Locations:
city: Bakersfield
country: United States
facility: Comprehensive Blood and Cancer Center, Research Department
state: California
city: Beverly Hills
country: United States
facility: Tower Cancer Research Foundation
state: California
city: Colorado Springs
country: United States
facility: Cancer Center of Colorado Springs, The Oncology Clinic, PC
state: Colorado
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers, LLP
state: Colorado
city: Washington
country: United States
facility: Washington Cancer Institute
state: District of Columbia
city: New Port Richey
country: United States
facility: Florida Cancer Institute
state: Florida
city: Ocoee
country: United States
facility: Cancer Centers of Florida, P.A.
state: Florida
city: Joliet
country: United States
facility: Joliet Oncology-Hematology Associates, Ltd.
state: Illinois
city: Peoria
country: United States
facility: Oncology/Hematology Associates of Central Illinois, PC
state: Illinois
city: Indianapolis
country: United States
facility: Central Indiana Cancer Centers
state: Indiana
city: Metairie
country: United States
facility: Hematology & Oncology Specialists LLC
state: Louisiana
city: Lansing
country: United States
facility: Great Lakes Cancer Institute Breslin Cancer Center
state: Michigan
city: Saint Louis
country: United States
facility: The Center for Cancer Care and Research
state: Missouri
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Kettering
country: United States
facility: Greater Dayton Cancer Center
state: Ohio
city: Pittsburgh
country: United States
facility: Western Pennsylvania Cancer Institute
state: Pennsylvania
city: Aberdeen
country: United States
facility: Oncology Services of Aberdeen
state: South Dakota
city: Sioux Falls
country: United States
facility: Avera Cancer Institute Leukemia-Bone Marrow Transplant Center
state: South Dakota
city: Johnson City
country: United States
facility: McLeod Cancer and Blood Center
state: Tennessee
city: Nashville
country: United States
facility: The Sarah Cannon Research Institute
state: Tennessee
city: Bedford
country: United States
facility: Texas Oncology, P.A.
state: Texas
city: Dallas
country: United States
facility: Texas Cancer Center at Medical City
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology, PA
state: Texas
city: Fredericksburg
country: United States
facility: San Antonio Tumor & Blood Clinic
state: Texas
city: San Antonio
country: United States
facility: Cancer Care Centers of South Texas - HOAST
state: Texas
city: Norfolk
country: United States
facility: Virginia Oncology Associates - Lake Wright Cancer Center
state: Virginia
city: Burien
country: United States
facility: Highline Medical Oncology
state: Washington
city: Edmonds
country: United States
facility: Puget Sound Cancer Center
state: Washington
city: Seattle
country: United States
facility: Puget Sound Cancer Center
state: Washington
city: Spokane
country: United States
facility: Cancer Care Northwest
state: Washington
city: Vancouver
country: United States
facility: Northwest Cancer Specialists, P.C.
state: Washington
Study officials:
affiliation: Celgene Corporation
name: CL Beach
role: STUDY_DIRECTOR
References:
citation: R. Lyons, et al. Rapid onset of effectiveness with three alternative azacitidine (aza) dosing regimens in patients (pts) with myelodysplastic syndromes (MDS). Haematologica 2008;93(suppl 1):Abs.0232.
citation: Lyons R, et al. Tolerability and hematologic improvement assessed using three alternative dosing schedules of azacitidine in patients with myelodysplastic syndromes. Presented at the 2007 ASCO Annual Meeting, June 1-5, 2007, Chicago, IL. Abstract No. 7083
citation: Komrokji R, Swern AS, Grinblatt D, Lyons RM, Tobiasson M, Silverman LR, Sayar H, Vij R, Fliss A, Tu N, Sugrue MM. Azacitidine in Lower-Risk Myelodysplastic Syndromes: A Meta-Analysis of Data from Prospective Studies. Oncologist. 2018 Feb;23(2):159-170. doi: 10.1634/theoncologist.2017-0215. Epub 2017 Nov 8.