Find-A-Study

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

Purpose

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.

Study Contact

Principal Investigator
Anne-Marie Langevin

Virginia Diaz
(210) 562-9149
diazvr@uthscsa.edu

Eligibility

Eligible Ages: Under29 Years
Eligible Genders: All
Accepts Healthy Volunteers: No

Inclusion Criteria

Patients must be newly diagnosed with de novo acute myelogenous leukemia
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
- 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
Patients with < 20% bone marrow 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
- The unequivocal presence of megakaryoblasts, or
- Biopsy proven isolated myeloid sarcoma (myeloblastoma; chloroma, including leukemia cutis)
Patients with any performance status are eligible for enrollment
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

Exclusion Criteria

Patients with any of the following constitutional conditions are not eligible:
- Fanconi anemia
- Shwachman syndrome
- Any other known bone marrow failure syndrome
- 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
Patients with any of the following oncologic diagnoses are not eligible:
- Any concurrent malignancy
- Juvenile myelomonocytic leukemia (JMML)
- Philadelphia chromosome positive AML
- Biphenotypic or bilineal acute leukemia
- Acute promyelocytic leukemia
- Acute myeloid leukemia arising from myelodysplasia
- Therapy-related myeloid neoplasms Note: enrollment may occur pending results of clinically indicated studies to exclude these conditions
Pregnancy and breast feeding
Female patients who are pregnant are ineligible
Lactating females are not eligible unless they have agreed not to breastfeed their infants
Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained
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

Study Design

Phase: Phase 3
Study Type: Interventional
Allocation: Randomized
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Masking: None (Open Label)
Condition: Acute Myeloid Leukemia
Leukemia Cutis
Myeloid Neoplasm
Myeloid Sarcoma

Arm Groups

Arm	Description	Intervention
Experimental Arm B	See Detailed Description	Drug: Asparaginase Given IM Other names: ASP-1 Asparaginase II Asparaginase-E.Coli Colaspase Elspar Kidrolase L-Asnase L-ASP L-Asparaginase L-Asparagine Amidohydrolase Laspar Lcf-ASP Drug: Cytarabine Given IT or IV Other names: .beta.-Cytosine arabinoside 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone 1-.beta.-D-Arabinofuranosylcytosine 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone 1-Beta Drug: Etoposide Given IV Other names: Demethyl Epipodophyllotoxin Ethylidine Glucoside EPEG Lastet Toposar Vepesid VP 16 VP 16-213 VP-16 VP-16-213 VP16 Drug: Mitoxantrone Hydrochloride Given IV Other names: CL 232315 DHAD DHAQ Dihydroxyanthracenedione Dihydrochloride Mitoxantrone Dihydrochloride Mitoxantroni Hydrochloridum Mitozantrone Hydrochloride Mitroxone N Other: Quality-of-Life Assessment Ancillary studies Other names: Quality of Life Assessment Drug: Bortezomib Given IV Other names: [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid LDP 341 MLN341 PS-341 PS341 Velcade Drug: Daunorubicin Hydrochloride Given IV Other names: Cerubidin Cerubidine Cloridrato de Daunorubicina Daunoblastin Daunoblastina Daunoblastine Daunomycin Hydrochloride Daunomycin, hydrochloride Daunorubicin.HC Other: Laboratory Biomarker Analysis Correlative studies Other: Pharmacological Study Correlative studies Other: Questionnaire Administration Ancillary studies
Experimental Arm C (Cohort 2)	See Detailed Description.	Drug: Asparaginase Given IM Other names: ASP-1 Asparaginase II Asparaginase-E.Coli Colaspase Elspar Kidrolase L-Asnase L-ASP L-Asparaginase L-Asparagine Amidohydrolase Laspar Lcf-ASP Drug: Cytarabine Given IT or IV Other names: .beta.-Cytosine arabinoside 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone 1-.beta.-D-Arabinofuranosylcytosine 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone 1-Beta Drug: Etoposide Given IV Other names: Demethyl Epipodophyllotoxin Ethylidine Glucoside EPEG Lastet Toposar Vepesid VP 16 VP 16-213 VP-16 VP-16-213 VP16 Drug: Mitoxantrone Hydrochloride Given IV Other names: CL 232315 DHAD DHAQ Dihydroxyanthracenedione Dihydrochloride Mitoxantrone Dihydrochloride Mitoxantroni Hydrochloridum Mitozantrone Hydrochloride Mitroxone N Other: Quality-of-Life Assessment Ancillary studies Other names: Quality of Life Assessment Drug: Sorafenib Tosylate Given PO Other names: BAY 43-9006 Tosylate BAY 54-9085 Nexavar sorafenib Drug: Daunorubicin Hydrochloride Given IV Other names: Cerubidin Cerubidine Cloridrato de Daunorubicina Daunoblastin Daunoblastina Daunoblastine Daunomycin Hydrochloride Daunomycin, hydrochloride Daunorubicin.HC Other: Laboratory Biomarker Analysis Correlative studies Other: Pharmacological Study Correlative studies Other: Questionnaire Administration Ancillary studies
Experimental Arm D	See Detailed Description. May reassigned to Arm C.	Drug: Cytarabine Given IT or IV Other names: .beta.-Cytosine arabinoside 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone 1-.beta.-D-Arabinofuranosylcytosine 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone 1-Beta Drug: Etoposide Given IV Other names: Demethyl Epipodophyllotoxin Ethylidine Glucoside EPEG Lastet Toposar Vepesid VP 16 VP 16-213 VP-16 VP-16-213 VP16 Other: Quality-of-Life Assessment Ancillary studies Other names: Quality of Life Assessment Drug: Daunorubicin Hydrochloride Given IV Other names: Cerubidin Cerubidine Cloridrato de Daunorubicina Daunoblastin Daunoblastina Daunoblastine Daunomycin Hydrochloride Daunomycin, hydrochloride Daunorubicin.HC Other: Laboratory Biomarker Analysis Correlative studies Other: Pharmacological Study Correlative studies Other: Questionnaire Administration Ancillary studies
Experimental Arm A	See Detailed Description	Drug: Asparaginase Given IM Other names: ASP-1 Asparaginase II Asparaginase-E.Coli Colaspase Elspar Kidrolase L-Asnase L-ASP L-Asparaginase L-Asparagine Amidohydrolase Laspar Lcf-ASP Drug: Cytarabine Given IT or IV Other names: .beta.-Cytosine arabinoside 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone 1-.beta.-D-Arabinofuranosylcytosine 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone 1-Beta Drug: Etoposide Given IV Other names: Demethyl Epipodophyllotoxin Ethylidine Glucoside EPEG Lastet Toposar Vepesid VP 16 VP 16-213 VP-16 VP-16-213 VP16 Drug: Mitoxantrone Hydrochloride Given IV Other names: CL 232315 DHAD DHAQ Dihydroxyanthracenedione Dihydrochloride Mitoxantrone Dihydrochloride Mitoxantroni Hydrochloridum Mitozantrone Hydrochloride Mitroxone N Other: Quality-of-Life Assessment Ancillary studies Other names: Quality of Life Assessment Drug: Daunorubicin Hydrochloride Given IV Other names: Cerubidin Cerubidine Cloridrato de Daunorubicina Daunoblastin Daunoblastina Daunoblastine Daunomycin Hydrochloride Daunomycin, hydrochloride Daunorubicin.HC Other: Laboratory Biomarker Analysis Correlative studies Other: Pharmacological Study Correlative studies Other: Questionnaire Administration Ancillary studies
Experimental Arm C (Cohort 1)	See Detailed Description	Drug: Asparaginase Given IM Other names: ASP-1 Asparaginase II Asparaginase-E.Coli Colaspase Elspar Kidrolase L-Asnase L-ASP L-Asparaginase L-Asparagine Amidohydrolase Laspar Lcf-ASP Drug: Cytarabine Given IT or IV Other names: .beta.-Cytosine arabinoside 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone 1-.beta.-D-Arabinofuranosylcytosine 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone 1-Beta Drug: Etoposide Given IV Other names: Demethyl Epipodophyllotoxin Ethylidine Glucoside EPEG Lastet Toposar Vepesid VP 16 VP 16-213 VP-16 VP-16-213 VP16 Drug: Mitoxantrone Hydrochloride Given IV Other names: CL 232315 DHAD DHAQ Dihydroxyanthracenedione Dihydrochloride Mitoxantrone Dihydrochloride Mitoxantroni Hydrochloridum Mitozantrone Hydrochloride Mitroxone N Other: Quality-of-Life Assessment Ancillary studies Other names: Quality of Life Assessment Drug: Sorafenib Tosylate Given PO Other names: BAY 43-9006 Tosylate BAY 54-9085 Nexavar sorafenib Drug: Daunorubicin Hydrochloride Given IV Other names: Cerubidin Cerubidine Cloridrato de Daunorubicina Daunoblastin Daunoblastina Daunoblastine Daunomycin Hydrochloride Daunomycin, hydrochloride Daunorubicin.HC Other: Laboratory Biomarker Analysis Correlative studies Other: Pharmacological Study Correlative studies Other: Questionnaire Administration Ancillary studies
Experimental Arm C (Cohort 3)	See Detailed Description. Different dose.	Drug: Asparaginase Given IM Other names: ASP-1 Asparaginase II Asparaginase-E.Coli Colaspase Elspar Kidrolase L-Asnase L-ASP L-Asparaginase L-Asparagine Amidohydrolase Laspar Lcf-ASP Drug: Cytarabine Given IT or IV Other names: .beta.-Cytosine arabinoside 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone 1-.beta.-D-Arabinofuranosylcytosine 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone 1-Beta Drug: Etoposide Given IV Other names: Demethyl Epipodophyllotoxin Ethylidine Glucoside EPEG Lastet Toposar Vepesid VP 16 VP 16-213 VP-16 VP-16-213 VP16 Drug: Mitoxantrone Hydrochloride Given IV Other names: CL 232315 DHAD DHAQ Dihydroxyanthracenedione Dihydrochloride Mitoxantrone Dihydrochloride Mitoxantroni Hydrochloridum Mitozantrone Hydrochloride Mitroxone N Other: Quality-of-Life Assessment Ancillary studies Other names: Quality of Life Assessment Drug: Sorafenib Tosylate Given PO Other names: BAY 43-9006 Tosylate BAY 54-9085 Nexavar sorafenib Drug: Daunorubicin Hydrochloride Given IV Other names: Cerubidin Cerubidine Cloridrato de Daunorubicina Daunoblastin Daunoblastina Daunoblastine Daunomycin Hydrochloride Daunomycin, hydrochloride Daunorubicin.HC Other: Laboratory Biomarker Analysis Correlative studies Other: Pharmacological Study Correlative studies Other: Questionnaire Administration Ancillary studies