1. Phase 3 randomized trial of chemotherapy with or without oblimersen in older AML patients: CALGB 10201 (Alliance)
- Author
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Robert K. Stuart, Grerk Sutamtewagul, Ann-Kathrin Eisfeld, Ravi Vij, Krzysztof Mrózek, Jessica Kohlschmidt, Mohan Thakuri, Richard Stone, William Blum, Wendy Stock, Andrew J. Carroll, Jonathan E. Kolitz, Richard A. Larson, Guido Marcucci, Eunice S. Wang, Clara D. Bloomfield, Jun Yin, John C. Byrd, Alison Walker, and Sawyer B. Jacobson
- Subjects
0301 basic medicine ,Oncology ,medicine.medical_specialty ,Myeloid ,Clinical Trials and Observations ,Daunorubicin ,Chronic lymphocytic leukemia ,medicine.medical_treatment ,03 medical and health sciences ,0302 clinical medicine ,hemic and lymphatic diseases ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,neoplasms ,Aged ,Chemotherapy ,business.industry ,Oblimersen ,Cytarabine ,Hematology ,Thionucleotides ,medicine.disease ,Chemotherapy regimen ,Leukemia, Myeloid, Acute ,Leukemia ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,business ,medicine.drug - Abstract
Overexpression of B-cell leukemia/lymphoma 2 (BCL2) renders acute myeloid leukemia (AML) cells resistant to chemotherapy and has been associated with unfavorable outcomes. Oblimersen (G3139) is a phosphorothioate 18-mer antisense oligonucleotide directed against the first 6 BCL2 codons. In a phase 1 study of AML patients treated with G3139, cytarabine, and daunorubicin induction with cytarabine consolidation, no antisense-related toxicity was reported, and BCL2 downregulation occurred in patients achieving complete remission. In this phase 3 trial, untreated older AML patients were randomized to cytarabine (100 mg/m2 per day on days 4-10) and daunorubicin (60 mg/m2 per day on days 4-6) followed by cytarabine consolidation (2000 mg/m2 per day on days 4-8) with (arm A) or without (arm B) G3139 (7 mg/m2 per day on days 1-10 [induction] or days 1-8 [consolidation]). A total of 506 patients were enrolled. No differences in toxicity were observed between arms. Estimated overall survival (OS) at 1 year was 43% for arm A and 40% for arm B (1-sided log rank P = .13), with no differences in disease-free (DFS; P = .26) or event-free survival (P = .80). Subgroup analyses showed patients age
- Published
- 2021
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