A Phase III Randomized Trial for Patients With De Novo AML Using Bortezomib and Sorafenib (NSC# 681239, NSC# 724772) for Patients With High Allelic Ratio FLT3/ITD
This randomized phase III trial studies how well bortezomib and sorafenib tosylate work in treating patients with newly diagnosed acute myeloid leukemia. Bortezomib and sorafenib tosylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving bortezomib and sorafenib tosylate together with combination chemotherapy may be an effective treatment for acute myeloid leukemia.
PRIMARY OBJECTIVES:
I. To compare event-free survival (EFS) and overall survival (OS) in patients with de novo acute myeloid leukemia (AML) without high allelic ratio fms-like tyrosine kinase (FLT3)/internal tandem duplications (ITD)+ mutations who are randomized to standard therapy versus bortezomib/standard combination therapy.
II. To determine the feasibility of combining bortezomib with standard chemotherapy in patients with de novo AML.
III. To compare the OS and EFS of high-risk patients treated with intensive Induction II with historical controls from AAML03P1 and AAML0531.
IV. To determine the feasibility of administering sorafenib (sorafenib tosylate) with standard chemotherapy and in a one year maintenance phase in patients with de novo high allelic ratio FLT3/ITD+ AML.
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Patients must be newly diagnosed with de novo acute myelogenous leukemia;
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Patients with previously untreated primary AML who meet the customary criteria for AML with >=20% bone marrow blasts as set out in the 2008 World Health Organization (WHO) Myeloid Neoplasm Classification are eligible
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* Attempts to obtain bone marrow either by aspirate or biopsy must be made unless clinically prohibitive, in cases where it is clinically prohibitive, peripheral blood with an excess of 20% blasts and in which adequate flow cytometric and cytogenetics/fluorescent in situ hybridization (FISH) testing is feasible can be substituted for the marrow exam at diagnosis;
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Patients with <20% bone marrow blasts are eligible if they have:
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* A karyotypic abnormality characteristic of de novo AML (t(8,21)(q22,q22), inv(16)(p13q22) or t(16,16)(p13,q22) or 11q23 abnormalities
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* The unequivocal presence of megakaryoblasts, or
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* Biopsy proven isolated myeloid sarcoma (myeloblastoma; chloroma, including leukemia cutis);
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Patients with any performance status are eligible for enrollment;
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Prior therapy with hydroxyurea, all-trans retinoic acid (ATRA), corticosteroids (any route), and IT cytarabine given at diagnosis is allowed, hydroxyurea and ATRA must be discontinued prior to initiation of protocol therapy, patients who have previously received any other chemotherapy, radiation therapy or any other antileukemic therapy are not eligible for this protocol;
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Patients with any of the following constitutional conditions are not eligible:
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* Fanconi anemia
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* Shwachman syndrome
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* Any other known bone marrow failure syndrome
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* Patients with constitutional trisomy 21 or with constitutional mosaicism of trisomy 21 Note: enrollment may occur pending results of clinically indicated studies to exclude these conditions;
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Patients with any of the following oncologic diagnoses are not eligible:
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* Any concurrent malignancy
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* Juvenile myelomonocytic leukemia (JMML)
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* Philadelphia chromosome positive AML
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* Biphenotypic or bilineal acute leukemia
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* Acute promyelocytic leukemia
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* Acute myeloid leukemia arising from myelodysplasia
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* Therapy-related myeloid neoplasms Note: enrollment may occur pending results of clinically indicated studies to exclude these conditions;
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Please contact study team for additional inclusion/exclusion criteria;
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Antimetabolites, Antineoplastic
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Antineoplastic Agents, Phytogenic
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Molecular Mechanisms of Pharmacological Action
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Neoplasms by Histologic Type
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Neoplasms, Connective and Soft Tissue
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Physiological Effects of Drugs
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Topoisomerase II Inhibitors
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