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Pilot Study of Idarubicin-Based Intensive-Timing Induction Therapy for Children With Previously Untreated Acute Myeloid Leukemia: Children's Cancer Group Study 2941

From the Children's Hospital of Philadelphia, Philadelphia, PA; Food and Drug Administration; Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Mayo Clinic, Rochester, MN; Izaak W. Killam Hospital for Children; University of California Los Angeles School of Medicine; Children's Hospital of Los Angeles, Los Angeles; Children's Hospital of Oakland, Oakland; Children’s Oncology Group, Arcadia, CA; and Children's National Medical Center, Washington, DC.

Address reprint requests to Shaun Mason, Children's Oncology Group, PO Box 60012, Arcadia, CA 91066-6012; e-mail: smason{at}childrensoncologygroup.org

PURPOSE: Randomized comparisons of idarubicin (IDA) with daunorubicin (DNR) show that in adults with acute myeloid leukemia (AML), IDA achieves higher remission rates and longer remission durations. In Children's Cancer Group Pilot Study CCG-2941, we assessed toxicity and feasibility of substituting 4 mg of DNR with 1 mg of IDA in intensive-timing daunorubicin-based induction therapy (DNR/DNR) used in CCG-2891.

PATIENTS AND METHODS: On days 1 through 3 and 10 through 14, patients received two courses of dexamethasone, cytarabine, 6-thioguanine, etoposide, and IDA (IDA/IDA). After enrollment of 65 patients, toxicity prompted replacement of IDA with DNR (IDA/DNR) on days 10 through 14 for the remaining 28 patients. Outcomes were compared with those of intensive timing in CCG-2891.

RESULTS: Treatment-related mortality after two courses of induction was not significantly different among the three regimens: 14% with IDA/IDA, 7% with IDA/DNR, and 9% with DNR/DNR. In course 1 of CCG-2941 IDA/IDA, 11% of patients withdrew compared with 1.5% in CCG-2891 (P < .001) and 5% in CCG-2941 IDA/DNR (P = not significant). Compared with CCG-2891 DNR/DRN, CCG-2941 IDA/IDA increased days in hospital (43 v 36 days; P = .007), mean duration of course 1 by a week (P = .002), and risk of grade 3 or 4 hyperbilirubinemia (18% v 5%; P = .02). Toxicity of IDA/DNR was not different from that of DNR/DNR in CCG-2891. The mean day 7 marrow blast percentage was 11.4% in CCG-2941 versus 21.1% in CCG-2891 (P = .004). Remission induction, survival, and event-free survival rates were not significantly different from those of CCG-2891.

CONCLUSION: In CCG-2941, excessive toxicity and withdrawals outweighed potential benefits of early response with IDA.

The work was supported by the following institutional grants from the National Institutions of Health. B.J.L.'s contributions were supported by the Yetta Dietch Novotny Chair in Clinical Oncology.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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