AAML1031: A Phase III Randomized Trial for Patients with de Novo AML using Bortezomib and Sorafenib for Patients with High Allelic Ratio
What is the purpose of this study?
This randomized phase II/III trial is studying how well giving bortezomib and sorafenib tosylate together works in treating patients with newly diagnosed acute myeloid leukemia with or without mutations.
Who can participate?
Up to 29 years of age.
- Patients must be newly diagnosed with de novo acute myelogenous leukemia and must meet 1 of the following criteria:
- Patients with previously untreated primary AML who meet the customary criteria for AML with ≥ 20% bone marrow blasts as set out in the 2008 WHO Myeloid Neoplasm Classification are eligible
- Patients with cytopenias and bone marrow blasts who do not meet the customary criteria for the diagnosis of AML (patients with < 20% blasts) are eligible if they have 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), or if they have the unequivocal presence of megakaryoblasts, as set out in the 2008 WHO Myeloid Neoplasm Classification
- Patients with biopsy-proven isolated myeloid sarcoma (myeloblastoma; chloroma, including leukemia cutis) are eligible
- Patients must meet one of the following criteria:
- Low-risk disease as defined by any of the following:
- Presence of inv(16)/t(16;16) or t(8;21) cytogenetic features or NPM or CEBPα mutation regardless of monosomy 7, monosomy 5, or del5q and regardless of MRD at end of Induction I
- Negative MRD (< 0.1%) at end of Induction I and no high-risk disease features
- Patients who do not have MRD data and have non-informative molecular studies (NPM, CEBPα, and cytogenetics) will be classified as having low-risk disease
- High-risk disease as defined by any of the following:
- FLT3/ITD+ with high allelic ratio > 0.4 (HR FLT3/ITD+) regardless of low-risk features
- Presence of monosomy 7, monosomy 5, or del5q, without inv(16)/t(16;16) or t(8;21) cytogenetics or NPM or CEBPα mutations
- AML without inv(16)/t(16;16), t(8;21), NPM, CEPBα mutations, monosomy 7, monosomy 5, del5q, or HR FLT3/ITD+, but with evidence of residual AML (≥ 0.1%) at end of Induction I
- Patients with juvenile myelomonocytic leukemia (JMML) are not eligible
- Patients with Philadelphia chromosome positive AML, biphenotypic or bilineal acute leukemia, or acute promyelocytic leukemia are not eligible
- High-risk patients may have a donor (bone marrow or cord blood) meeting the following criteria available:
- Matched family donor (MFD)*
- HLA, A, B, C, DRB1, identical, or 1 antigen or allele mismatched
- HLA typing must be performed using molecular high-resolution technique
- All available first-degree family members (parents and siblings) must be HLA typed
- Use of syngeneic donors will NOT be permitted in this study NOTE: *For MFD SCT, the use of peripheral blood stem cells (PBSC) is not permitted on this study.
- HLA, A, B, C, DRB1 identical or 1 antigen- or allele-mismatched unrelated donor
- HLA A, B, DRB1 4 of 6 antigen-matched unrelated donor cord blood unit with an adequate cell dose (nucleated cell dose > 3.7x10^7/kg or CD34+ cell dose > 2 x 10^5/kg)
- Mismatched family member donor with at least one haplotype match, or 5 of 6 antigen phenotypic match
- Patients with any performance status are eligible
- Patients with constitutional trisomy 21 are not eligible
- Patients with any of the following are not eligible:
- Fanconi anemia
- Shwachman syndrome
- Any other known bone marrow failure syndrome
- Another concurrent malignancy
- Not pregnant or nursing
- Negative pregnancy test
- Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation
- Adult Studies
- Cancer - Leukemia and Lymphoma
Who should I contact for more information?
Cincinnati Children’s Hospital Medical Center
Division of Hematology/Oncology
3333 Burnet Ave., Cincinnati, OH 45229-3039
Where can I find additional information?