Bortezomib and Sorafenib Tosylate in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

Status: Recruiting
Phase: Phase 3
Diagnosis: Pediatric Leukemia
NCT ID: NCT01371981 (View complete trial on
DFCI Protocol ID: 13-120


This randomized phase II/III trial studies how well bortezomib and sorafenib tosylate together works in treating patients with newly diagnosed acute myeloid leukemia with or without mutations. 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 more than one drug (combination chemotherapy) may kill more cancer cells. Giving bortezomib and sorafenib tosylate together with combination chemotherapy may be an effective treatment for acute myeloid leukemia. [acute myelogenous leukemia]


Conducting Institutions:
Dana-Farber Cancer Institute, Children's Hospital Boston, Massachusetts General Hospital

Overall PI:
Steven Margossian, MD, PhD, Dana Farber Cancer Institute

Site-responsible Investigators:
Howard Weinstein, MD, Massachusetts General Hospital

Dana-Farber Cancer Institute: Childrens Hospital Pediatric Clinical Translation Investigation Program CTIP,
Massachusetts General Hospital: Cancer Trials Call Center, 877-789-6100

Eligibility Criteria

Inclusion Criteria: - 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 diagnosisof AML (patients with < 20% blasts) are eligible if they have a karyotypic abnormality characteristic ofde novo AML (t(8;21)(q22;q22), inv(16)(p13q22) or t(16;16)(p13;q22) or 11q23 abnormalities), or ifthey have the unequivocal presence of megakaryoblasts, as set out in the 2008 WHO Myeloid NeoplasmClassification - Patients with biopsy-proven isolated myeloid sarcoma (myeloblastoma; chloroma, including leukemiacutis) 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)] or presence of NPM orCEBPα mutation, regardless of minimum-residual disease (MRD) status at end of Induction I - Standard-risk cytogenetics (neitherfavorable or unfavorable) with negative MRD (< 0.1%) at end of Induction I - 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 (HR FLT3/ITD+) - Unfavorablecytogenetics (monosomy 7, monosomy 5, and del5q) - Standard-risk cytogenetics with positive MRD(≥ 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 - Alternative donor - 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 adequatecell 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 antigenphenotypic 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 aneffective contraceptive method for the duration of their study participation - Prior therapy with hydroxyurea, all-trans retinoic acid (ATRA), corticosteroids (any route), and intrathecal (IT) cytarabinegiven at diagnosis is allowed - Hydroxyurea and ATRA must be discontinued prior to initiation of protocoltherapy - No concurrent peripheral blood stem cell transplantation - Patients who have previously received any other chemotherapy, radiation therapy, or any otherantileukemic therapy are not eligible for this protocol - Concomitant administration of strong CYP3A4 inducers and inhibitors (including clinicallyrelevant moderate inhibitors) is prohibited on both sorafenib cohorts
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