Alternative Dosing Regimens of Subcutaneous Azacitidine for Myelodysplastic Syndromes

Celgene151 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

151

Conditions

Myelodysplastic Syndromes

Interventions

azacitidineDRUG

Azacitidine is administered subcutaneously Total of 18 cycles on treatment or early discontinuation.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (31)

Outcomes

Primary Outcomes

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)

Time frame: Day 1 (randomization) to 6 months

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)

Time frame: Day 1 (randomization) to 6 months

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.

Time frame: Day 1 (randomization) to 6 months

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

Data from ClinicalTrials.gov

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Comprehensive Blood and Cancer Center, Research Department

Bakersfield, California, United States

Tower Cancer Research Foundation

Beverly Hills, California, United States

Cancer Center of Colorado Springs, The Oncology Clinic, PC

Colorado Springs, Colorado, United States

Rocky Mountain Cancer Centers, LLP

Denver, Colorado, United States

Washington Cancer Institute

Washington D.C., District of Columbia, United States

Florida Cancer Institute

New Port Richey, Florida, United States

Cancer Centers of Florida, P.A.

Ocoee, Florida, United States

Joliet Oncology-Hematology Associates, Ltd.

Joliet, Illinois, United States

Oncology/Hematology Associates of Central Illinois, PC

Peoria, Illinois, United States

Central Indiana Cancer Centers

Indianapolis, Indiana, United States

...and 21 more locations

Secondary Outcomes

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.

Time frame: Day 1 (randomization)

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.

Time frame: 6 months

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.

Time frame: 24 months

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.

Time frame: Day 1 (randomization)

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.

Time frame: 6 months

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.

Time frame: 24 months

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.

Time frame: Day 1 (randomization)

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.

Time frame: 6 months

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.

Time frame: 24 months

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.

Time frame: 6 months

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.

Time frame: 6 months

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.

Time frame: 24 months

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.

Time frame: 24 months

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).

Time frame: 6 months

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).

Time frame: 24 months