Alternative Dosing Regimens of Subcutaneous Azacitidine for Myelodysplastic Syndromes

Myelodysplastic Syndromes Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00102687
• Other study ID #: AZA PH US 2004 CL003
• Status: Completed
• Phase: Phase 2
• Start date: January 1, 2005
• Est. completion date: August 1, 2008

Study information

• Verified date: November 2019
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 151
• Est. completion date: August 1, 2008
• Est. primary completion date: August 1, 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Drug:
• azacitidine
Azacitidine is administered subcutaneously Total of 18 cycles on treatment or early discontinuation.

Locations

Country	Name	City	State
United States	Oncology Services of Aberdeen	Aberdeen	South Dakota
United States	Comprehensive Blood and Cancer Center, Research Department	Bakersfield	California
United States	Texas Oncology, P.A.	Bedford	Texas
United States	Tower Cancer Research Foundation	Beverly Hills	California
United States	Highline Medical Oncology	Burien	Washington
United States	Cancer Center of Colorado Springs, The Oncology Clinic, PC	Colorado Springs	Colorado
United States	Texas Cancer Center at Medical City	Dallas	Texas
United States	Rocky Mountain Cancer Centers, LLP	Denver	Colorado
United States	Puget Sound Cancer Center	Edmonds	Washington
United States	Texas Oncology, PA	Fort Worth	Texas
United States	San Antonio Tumor & Blood Clinic	Fredericksburg	Texas
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Central Indiana Cancer Centers	Indianapolis	Indiana
United States	McLeod Cancer and Blood Center	Johnson City	Tennessee
United States	Joliet Oncology-Hematology Associates, Ltd.	Joliet	Illinois
United States	Greater Dayton Cancer Center	Kettering	Ohio
United States	Great Lakes Cancer Institute Breslin Cancer Center	Lansing	Michigan
United States	Hematology & Oncology Specialists LLC	Metairie	Louisiana
United States	The Sarah Cannon Research Institute	Nashville	Tennessee
United States	Florida Cancer Institute	New Port Richey	Florida
United States	Virginia Oncology Associates - Lake Wright Cancer Center	Norfolk	Virginia
United States	Cancer Centers of Florida, P.A.	Ocoee	Florida
United States	Oncology/Hematology Associates of Central Illinois, PC	Peoria	Illinois
United States	Western Pennsylvania Cancer Institute	Pittsburgh	Pennsylvania
United States	The Center for Cancer Care and Research	Saint Louis	Missouri
United States	Cancer Care Centers of South Texas - HOAST	San Antonio	Texas
United States	Puget Sound Cancer Center	Seattle	Washington
United States	Avera Cancer Institute Leukemia-Bone Marrow Transplant Center	Sioux Falls	South Dakota
United States	Cancer Care Northwest	Spokane	Washington
United States	Northwest Cancer Specialists, P.C.	Vancouver	Washington
United States	Washington Cancer Institute	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Celgene

Country where clinical trial is conducted

United States, 

References & Publications (3)

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. — View 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

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.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Participant counts by best hematological response; complete remission(CR) is better than a partial remission(PR) which is better than stable disease(SD).; Investigator determined responses followed IWG 2000 criteria for MDS CR: repeat bone marrow show <5% myeloblasts, and peripheral blood evaluations lasting >=2 months of hemoglobin(>110 g/L), neutrophils(>=1.5x10^9/L), platelets(>=100x10^9/L), blasts (0%) and no dysplasia PR is the same as CR for peripheral blood: bone marrow shows blasts decrease by >=50% or a less advanced FAB classification from pretreatment (see Population Descrip)	Day 1 (randomization) to 6 months
Primary	Number of Participants With Best Hematological Improvement Derived Using International Working Group 2000 (IWG 2000) Criteria for MDS During the Initial Study Period.	IWG 2000 Criteria: Pretreatment=hemoglobin <110g/L or RBC transfusion-dependence, platelet count <100x10^9/L or platelet transfusion dependence, absolute neutrophil count <1.5x10^9/L.; Erythroid response: Major->20g/L increase in hemoglobin or transfusion independence. Minor- 10-20g/L increase in hemoglobin or >=50% decrease in transfusion requirements.; Platelet response: Major-absolute increase of platelet count by >=30x10^9/L or platelet transfusion independence. Minor->=50% increase in platelet count with net increase >10x10^9/L but <30x10^9/L.; (continued in Population Description)	Day 1 (randomization) to 6 months
Primary	Number of Participants With Overall Best Hematologic Response and Hematologic Improvement Based on IWG 2000 Criteria For MDS During the Initial Study Period	Number of participants whose best hematological outcome was either complete remission (CR), partial remission (PR) (as determined by the investigator), or any hematologic improvement (based on the IWG 2000 criteria for MDS). See previous outcomes for detailed definitions.	Day 1 (randomization) to 6 months
Primary	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	Hematologic response during the maintenance period are compared to the response in the initial study period. Initial response could have been a complete remission, a partial remission, stable disease or a hematologic improvement. Maintenance period best response is after randomization to a maintenance arm for those randomized, and is after the start of cycle 7 for those remaining on initial period treatment throughout the study.	24 months
Secondary	Baseline Hemoglobin Values	The median values for hemoglobin based on blood tests performed on study day 1 (prior to study treatment) constitute a baseline measure for hemoglobin. Baseline values are used to compare to values following treatment.	Day 1 (randomization)
Secondary	Change From Baseline in Hemoglobin at End of Initial Study Period (6 Months)	The difference between hemoglobin values at the end of the initial study period minus the hemoglobin values at baseline.	6 months
Secondary	Change From Baseline in Hemoglobin at the End of the Maintenance Study Period	The difference between hemoglobin values at the end of the maintenance study period minus the hemoglobin values at baseline.	24 months
Secondary	Baseline Platelet Values	The median values for platelets based on blood tests performed on study day 1 (prior to study treatment) constitute a baseline measure for platelets. Baseline values are used to compare to values following treatment.	Day 1 (randomization)
Secondary	Change From Baseline in Platelets at the End of Initial Study Period (6 Months)	The difference between platelet values at the end of the initial study period minus the platelet values at baseline.	6 months
Secondary	Change From Baseline in Platelets at the End of the Maintenance Study Period (Month 24)	The difference between platelet values at the end of the maintenance study period minus the platelet values at baseline.	24 months
Secondary	Baseline Absolute Neutrophil Count (ANC) Values	The median values for ANC based on blood tests performed on study day 1 (prior to study treatment) constitute a baseline measure for ANC. Baseline values are used to compare to values following treatment.	Day 1 (randomization)
Secondary	Change From Baseline in Absolute Neutrophil Count (ANC) at the End of Initial Study Period (6 Months)	The difference between ANC values at the end of the initial study period minus the ANC values at baseline.	6 months
Secondary	Change From Baseline in Absolute Neutrophil Count (ANC) at the End of the Maintenance Study Period (Month 24)	The difference between ANC values at the end of the maintenance study period minus the ANC values at baseline.	24 months
Secondary	Red Blood Cell (RBC) Transfusion Status at Baseline and End of Initial Study Period (6 Months)	Shift table comparing the RBC transfusion status of patients at the end of the initial study period to the transfusion status at baseline.	6 months
Secondary	Platelet Transfusion Status at Baseline and End of Initial Study Period (6 Months)	Shift table comparing the platelet transfusion status of patients at the end of the initial study period to the transfusion status at baseline.	6 months
Secondary	Red Blood Cell (RBC) Transfusion Status at Baseline and End of Maintenance Study Period (24 Months)	Shift table comparing the RBC transfusion status of patients at the end of the maintenance study period to the transfusion status at baseline.	24 months
Secondary	Platelet Transfusion Status at Baseline and End of Maintenance Study Period (24 Months)	Shift table comparing the platelet transfusion status of patients at the end of the maintenance study period to the transfusion status at baseline.	24 months
Secondary	Change From Baseline in the Number of Infections Requiring Treatment With IV Antibiotics Per Treatment Cycle (28 Days) for the Initial Study Period	Baseline uses the average number of infections requiring IV antibiotic treatment from the 28 days prior to and including the day of first dose to an initial treatment arm. Initial study period values total the number of infections requiring IV antibiotic treatment divided by the number of treatment cycles (each cycle is approximately one month).	6 months
Secondary	Change From Baseline in the Number of Infections Requiring Treatment With IV Antibiotics Per Treatment Cycle (28 Days) for the Maintenance Study Period	Baseline uses the average number of infections requiring IV antibiotic treatment from the 28 days prior to and including the day of first dose to an initial treatment arm. Maintenance study period values total the number of infections requiring IV antibiotic treatment divided by the number of treatment cycles (each cycle is approximately one month).	24 months