Alternative Dosing Regimens of Subcutaneous Azacitidine for Myelodysplastic Syndromes

NCT00102687 | Completed Phase 2 Results

• 1 other identifier: AZA PH US 2004 CL003
• Study Type: interventional
• Target: 151
• Locations: 1 country
• Sites: 31

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.

Conditions

Myelodysplastic Syndromes

Outcome Measures

Primary Outcomes (4)

• 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

• 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

• 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

• 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 Outcomes (15)

• Baseline Hemoglobin Values

  Day 1 (randomization)

• Change From Baseline in Hemoglobin at End of Initial Study Period (6 Months)

  6 months

• Change From Baseline in Hemoglobin at the End of the Maintenance Study Period

  24 months

• Baseline Platelet Values

  Day 1 (randomization)

• Change From Baseline in Platelets at the End of Initial Study Period (6 Months)

  6 months

Study Arms (5)

Aza-5

EXPERIMENTAL

Azacitidine administered subcutaneously at 75mg/m\^2 for 5 days on a 28 day cycle.

Drug: azacitidine

Aza-5-2-2

EXPERIMENTAL

Azacitidine administered subcutaneously at 75mg/m\^2 for 5days with 2 days off, then for an additional 2 days, on a 28 day cycle.

Drug: azacitidine

Aza-5-2-5

EXPERIMENTAL

Azacitidine administered subcutaneously at 50mg/m\^2 for 5 days with 2 days off, then for an additional 5 days, on a 28 day cycle.

Drug: azacitidine

Maintenance Aza 5 days q 4 weeks

EXPERIMENTAL

Azacitidine administered subcutaneously at 75mg/m\^2 for 5 days every 4 weeks.

Drug: azacitidine

Maintenance Aza 5 days q 6 weeks

EXPERIMENTAL

Azacitidine administered subcutaneously at 75mg/m\^2 for 5 days every 6 weeks.

Drug: azacitidine

Interventions

azacitidine DRUG

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

Aza-5; Aza-5-2-2; Aza-5-2-5; Maintenance Aza 5 days q 4 weeks; Maintenance Aza 5 days q 6 weeks

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Celgene: lead

Study Sites (31)

Comprehensive Blood and Cancer Center, Research Department

Bakersfield, California, 93309, United States

Location

Tower Cancer Research Foundation

Beverly Hills, California, 90211, United States

Location

Cancer Center of Colorado Springs, The Oncology Clinic, PC

Colorado Springs, Colorado, 80907, United States

Location

Rocky Mountain Cancer Centers, LLP

Denver, Colorado, 80218, United States

Location

Washington Cancer Institute

Washington D.C., District of Columbia, 20010, United States

Location

Florida Cancer Institute

New Port Richey, Florida, 34652, United States

Location

Cancer Centers of Florida, P.A.

Ocoee, Florida, 34761, United States

Location

Joliet Oncology-Hematology Associates, Ltd.

Joliet, Illinois, 60435, United States

Location

Oncology/Hematology Associates of Central Illinois, PC

Peoria, Illinois, 61615-7828, United States

Location

Central Indiana Cancer Centers

Indianapolis, Indiana, 46227, United States

Location

Hematology & Oncology Specialists LLC

Metairie, Louisiana, 70115, United States

Location

Great Lakes Cancer Institute Breslin Cancer Center

Lansing, Michigan, 48910, United States

Location

The Center for Cancer Care and Research

St Louis, Missouri, 63141, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Greater Dayton Cancer Center

Kettering, Ohio, 45409, United States

Location

Western Pennsylvania Cancer Institute

Pittsburgh, Pennsylvania, 15224, United States

Location

Oncology Services of Aberdeen

Aberdeen, South Dakota, 57401, United States

Location

Avera Cancer Institute Leukemia-Bone Marrow Transplant Center

Sioux Falls, South Dakota, 57105, United States

Location

McLeod Cancer and Blood Center

Johnson City, Tennessee, 37604, United States

Location

The Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Texas Oncology, P.A.

Bedford, Texas, 76022, United States

Location

Texas Cancer Center at Medical City

Dallas, Texas, 75230, United States

Location

Texas Oncology, PA

Fort Worth, Texas, 76104, United States

Location

San Antonio Tumor & Blood Clinic

Fredericksburg, Texas, 78624, United States

Location

Cancer Care Centers of South Texas - HOAST

San Antonio, Texas, 78229, United States

Location

Virginia Oncology Associates - Lake Wright Cancer Center

Norfolk, Virginia, 23502, United States

Location

Highline Medical Oncology

Burien, Washington, 98166, United States

Location

Puget Sound Cancer Center

Edmonds, Washington, 98026, United States

Location

Puget Sound Cancer Center

Seattle, Washington, 98133, United States

Location

Cancer Care Northwest

Spokane, Washington, 99218, United States

Location

Northwest Cancer Specialists, P.C.

Vancouver, Washington, 98684, United States

Location

Related Publications (3)

• 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.

  BACKGROUND

• 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

  BACKGROUND

• 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.

  PMID: 29118268 BACKGROUND

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

Azacitidine

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: CL Beach
• Organization: Celgene Corporation

CLBeach@celgene.com

Study Officials

• CL Beach

  Celgene Corporation

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 31, 2005
• First Posted: February 1, 2005
• Study Start: January 1, 2005
• Primary Completion: August 1, 2008
• Study Completion: August 1, 2008
• Last Updated: November 22, 2019
• Results First Posted: May 28, 2010

Record last verified: 2019-11

Locations

US (31)