Design and rationale of the QUAZAR Lower-Risk MDS (AZA-MDS-003) trial: a randomized phase 3 study of CC-486 (oral azacitidine) plus best supportive care vs placebo plus best supportive care in patients with IPSS lower-risk myelodysplastic syndromes and poor prognosis due to red blood cell transfusion–dependent anemia and thrombocytopenia

BMC Hematology

Study Protocol

Barry Skikne¹  Guillermo Garcia-Manero²  Valeria Santini³  Regina Garcia⁴  David Valcarcel⁵  Antonio Almeida⁶  Aristoteles Giagounidis⁷  Uwe Platzbecker⁸  Lewis R. Silverman⁹  Stephen R. Larsen^1,10  Maria Teresa Voso^1,11 

[1] Celgene Corporation, Overland Park, KS, USA;Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA;Hematology, University of Florence, AOU Careggi, Florence, Italy;Hospital Clinico Universitario Virgen de la Victoria, Malaga, Spain;Hospital Vall D’Hebron, Barcelona, Spain;Instituto Portugues de Oncologia Francisco Gentil, Lisbon, Portugal;Marien-Hospital Akademisches Lehrkrankenhaus, Dusseldorf, Germany;Medizinschen Fakultat Carl Gustav Carus der TU Dresden, Dresden, Germany;Mount Sinai School of Medicine, New York, NY, USA;Royal Prince Alfred Hospital, Sydney, Australia;Universita Cattolica del Sacro Cuore, Rome, Italy;

关键词: Myelodysplastic syndromes;    MDS;    IPSS lower risk;    CC-486;    Azacitidine;    Red blood cell transfusion dependence;    Anemia;    Thrombocytopenia;   

DOI  :  10.1186/s12878-016-0049-5

 received in 2015-04-14, accepted in 2016-04-14,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundCC-486 is an oral formulation of the epigenetic modifier azacitidine. In an expanded phase 1 trial, CC-486 demonstrated clinical and biological activity in patients with International Prognostic Scoring System (IPSS) lower-risk (low- and intermediate-1–risk) myelodysplastic syndromes (MDS) with poor prognostic features including anemia and/or thrombocytopenia who may have required red blood cell or platelet transfusions. The overall response rate was 40 %, including hematologic improvement in 28 % of patients and RBC transfusion independence sustained for 56 days in 47 % of patients with baseline transfusion dependence. Based on the results of this study, the randomized, placebo-controlled phase 3 QUAZAR Lower-Risk MDS trial (AZA-MDS-003) was initiated. The design and rationale for this trial comparing CC-486 with placebo for the treatment of patients with IPSS lower-risk MDS with poor prognostic features are described.MethodsPatients must have IPSS lower-risk MDS with red blood cell (RBC) transfusion–dependent anemia and thrombocytopenia. Eligible patients are randomized 1:1 to receive 300 mg of CC-486 or placebo once daily for the first 21 days of 28-day treatment cycles. Disease status assessments occur at the end of cycle 6 and patients may continue to receive treatment unless there is evidence of progressive disease, lack of efficacy, or unacceptable toxicity. The primary endpoint is RBC transfusion independence for ≥ 84 days, assessed according to International Working Group 2006 criteria. Secondary endpoints include overall survival, hematologic response including platelet response and erythroid response, RBC transfusion independence for ≥ 56 days, duration of RBC transfusion independence, time to RBC transfusion independence, rate of acute myeloid leukemia (AML) progression, time to AML progression, clinically significant bleeding events, safety, health-related quality of life, and healthcare resource utilization.ConclusionsThis study will provide data on the efficacy and safety of CC-486 in the treatment of IPSS lower-risk MDS with poor prognosis due to the presence of both RBC transfusion–dependent anemia and thrombocytopenia. Positive results of the AZA-MDS-003 study may expand treatment options for patients with IPSS lower-risk MDS.Trial registrationClinicalTrials.gov NCT01566695, registered March 27, 2012.

【 授权许可】

CC BY   
© Garcia-Manero et al. 2016