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

This study is currently recruiting participants.
Verified December 2013 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01371981
First received: June 10, 2011
Last updated: December 16, 2013
Last verified: December 2013
  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.


Condition Intervention Phase
Adult Acute Erythroid Leukemia (M6)
Adult Acute Megakaryoblastic Leukemia (M7)
Adult Acute Minimally Differentiated Myeloid Leukemia (M0)
Adult Acute Monoblastic Leukemia (M5a)
Adult Acute Monocytic Leukemia (M5b)
Adult Acute Myeloblastic Leukemia With Maturation (M2)
Adult Acute Myeloblastic Leukemia Without Maturation (M1)
Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
Adult Acute Myeloid Leukemia With Del(5q)
Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)
Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
Adult Acute Myelomonocytic Leukemia (M4)
Adult Pure Erythroid Leukemia (M6b)
Childhood Acute Erythroleukemia (M6)
Childhood Acute Megakaryocytic Leukemia (M7)
Childhood Acute Minimally Differentiated Myeloid Leukemia (M0)
Childhood Acute Monoblastic Leukemia (M5a)
Childhood Acute Monocytic Leukemia (M5b)
Childhood Acute Myeloblastic Leukemia With Maturation (M2)
Childhood Acute Myeloblastic Leukemia Without Maturation (M1)
Childhood Acute Myelomonocytic Leukemia (M4)
Untreated Adult Acute Myeloid Leukemia
Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies
Drug: asparaginase
Drug: daunorubicin hydrochloride
Drug: mitoxantrone hydrochloride
Drug: sorafenib tosylate
Drug: cytarabine
Drug: etoposide
Drug: bortezomib
Other: pharmacological study
Other: laboratory biomarker analysis
Other: questionnaire administration
Procedure: quality-of-life assessment
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase III Randomized Trial for Patients With de Novo AML Using Bortezomib and Sorafenib (IND#114480; NSC# 681239, NSC# 724772) for Patients With High Allelic Ratio FLT3/ITD

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Event-free survival [ Time Frame: From the time on study to induction failure, relapse or death, up to 11 years ] [ Designated as safety issue: No ]
    The Kaplan-Meier method will be used to estimate EFS.


Secondary Outcome Measures:
  • Overall survival [ Time Frame: Up to 11 years ] [ Designated as safety issue: No ]
    The Kaplan-Meier method will be used to estimate OS.

  • Remission rate after 1 course of therapy [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • Remission rate after 2 courses of therapy [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Proportion of patients dying in each course of therapy [ Time Frame: Up to 11 years ] [ Designated as safety issue: No ]
  • Course duration [ Time Frame: Up to 11 years ] [ Designated as safety issue: No ]
  • Length of hospitalization [ Time Frame: Up to 11 years ] [ Designated as safety issue: No ]
    Descriptive statistics will be used to summarize length of hospitalization time.

  • Time to blood count recovery [ Time Frame: Up to 11 years ] [ Designated as safety issue: No ]
    Cumulative incidence estimates that account for competing events will be used to estimate time to count recovery.

  • Relapse rate assessed by bone marrow analsysis for leukemic blasts [ Time Frame: Up to 11 years ] [ Designated as safety issue: No ]
    Cumulative incidence estimates that account for competing events will be used to estimate relapse rate.

  • Incidence of treatment-related mortality [ Time Frame: Up to 11 years ] [ Designated as safety issue: No ]
    Cumulative incidence estimates that account for competing events will be used to estimate treatment-related mortality.

  • Proportion of patients expereincing grade 3 or higher non-hematologic toxicities and infections assessed by Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0) [ Time Frame: Up to 11 years ] [ Designated as safety issue: Yes ]
    The proportion of patients experiencing grade 3 or higher non-hematologic toxicities and infections will be estimated.

  • Proportion of high risk children without HR FLT3/ITD+ converting from positive MRD at end of Induction I to negative MRD at the end of Induction II [ Time Frame: Up to 11 years ] [ Designated as safety issue: No ]
    The proportion of high risk children without HR FLT3/ITD+ converting from positive MRD at end of Induction I to negative MRD at the end of Induction II will be estimated as well as the corresponding confidence interval. In addition, this proportion will be compared with the proportion for high risk children without HR FLT3/ITD+ treated on AAML03P1 and AAML0531.

  • Parent-reported questionnaire scores [ Time Frame: At 4 months following start of SCT or intensification II of chemotherapy ] [ Designated as safety issue: No ]
    Questionnaires include the Generic Core Scale, Acute Cancer Module, and Multidimensional Fatigue Module summary and dimension scores of HRQOL and Pediatric Inventory for Parents (PIP). Mean values and their 95% confidence intervals (CI) will be presented.

  • Change in parent-reported outcomes over time in recipients of SCT or chemotherapy [ Time Frame: Baseline to up to 11 years ] [ Designated as safety issue: No ]
    Summary measures at each time point as well as the overall trajectory over time in HRQOL and PIP will be described. A mixed linear regression model with repeated measures incorporating covariates as appropriate will be performed.

  • Bortezomib pharmacokinetic plasma concentration-time profiles [ Time Frame: Day 8 of induction I ] [ Designated as safety issue: No ]
    Analyzed using descriptive statistics and will be graphically displayed by age group. PK data will be analyzed using methods such as nonlinear mixed effects modeling to estimate bortezomib clearance (Cl) and volume of distribution (Vd) with associated 95% confidence intervals in each age group (2-11 years and 12-16 years of age).

  • Systemic exposure of sorafenib and N-oxide metabolite for each course of induction and intensification (CL, Vd, time to maximum concentration [Tmax]½, area under curve [AUC]) [ Time Frame: Up to 11 years ] [ Designated as safety issue: No ]
    Descriptive statistics will be used to summarize the systemic exposure of sorafenib and N-oxide metabolite for each course of induction and intensification (CL, Vd, Tmax½, AUC). If sufficient data is available, comparison to steady state pharmacokinetic data from ADVL0413 will be performed using Wilcoxon sign rank test. For PIA-PK correlations, a random effects linear regression model will be used to describe the relationship between plasma inhibitory assay and PK levels for each of the trough plasma samples collected for each patient.

  • Shortening fraction/ejection fraction percentages and change over time [ Time Frame: Up to 11 years ] [ Designated as safety issue: No ]
    Analyzed by repeated measures analysis of variance accounting for dexrazoxane exposure and other clinically relevant covariates, including age, gender, body mass index, risk group, and treatment arm.

  • Serum concentrations of GVHD biomarkers [ Time Frame: Up to day 28 after SCT ] [ Designated as safety issue: No ]
    Logistic regression modeling will be used to assign individual weights to each individual biomarker and clinical variable to maximize sensitivity and specificity of a mathematical algorithm for the prediction of grade 2-4 GVHD occurring on or before day 56 post-SCT. It will be tested whether algorithms using the day 7, 14, or 28 biomarker panel, or a combination of the biomarker panels at these different time points are most useful for the prediction of GVHD. The different algorithms will be compared on the basis of maximal specificity and sensitivity using the Akaike information criterion.


Estimated Enrollment: 1250
Study Start Date: June 2011
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Induction I, Arm A
Patients receive cytarabine IT on day 1 and ADE chemotherapy comprising cytarabine IV over 1-30 minutes on days 1-10; daunorubicin IV over 1-15 minutes on days 1, 3, and 5; and etoposide IV over 1-2 hours on days 1-5.
Drug: daunorubicin hydrochloride
Given IV
Other Names:
  • Cerubidin
  • Cerubidine
  • daunomycin hydrochloride
  • daunorubicin
  • RP-13057
Drug: cytarabine
Given IT or IV
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies
Other: questionnaire administration
Ancillary studies
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Experimental: Induction I, Arm B
Patients receive cytarabine IT and ADE chemotherapy as in Induction I, Arm A. Patients also receive bortezomib IV on days 1, 4, and 8.
Drug: daunorubicin hydrochloride
Given IV
Other Names:
  • Cerubidin
  • Cerubidine
  • daunomycin hydrochloride
  • daunorubicin
  • RP-13057
Drug: cytarabine
Given IT or IV
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Drug: bortezomib
Given IV
Other Names:
  • LDP 341
  • MLN341
  • VELCADE
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies
Other: questionnaire administration
Ancillary studies
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Experimental: Induction I, Arm C
Patients receive cytarabine IT and ADE chemotherapy as in Induction I, Arm A and sorafenib tosylate PO on days 11-28.
Drug: daunorubicin hydrochloride
Given IV
Other Names:
  • Cerubidin
  • Cerubidine
  • daunomycin hydrochloride
  • daunorubicin
  • RP-13057
Drug: sorafenib tosylate
Given PO
Other Names:
  • BAY 43-9006
  • BAY 43-9006 Tosylate Salt
  • BAY 54-9085
  • Nexavar
  • SFN
Drug: cytarabine
Given IT or IV
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies
Other: questionnaire administration
Ancillary studies
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Experimental: Induction II, Arm A (LR patients)
Patients receive cytarabine IT and ADE chemotherapy as in Induction I Arm A.
Drug: daunorubicin hydrochloride
Given IV
Other Names:
  • Cerubidin
  • Cerubidine
  • daunomycin hydrochloride
  • daunorubicin
  • RP-13057
Drug: cytarabine
Given IT or IV
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Other: laboratory biomarker analysis
Correlative studies
Other: questionnaire administration
Ancillary studies
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Experimental: Induction II, Arm A (HR patients)
Patients receive cytarabine IT on day 1 and MA chemotherapy comprising high-dose cytarabine IV over 1-3 hours on days 1-4, and mitoxantrone IV over 15-30 minutes on days 3-6.
Drug: mitoxantrone hydrochloride
Given IV
Other Names:
  • CL 232315
  • DHAD
  • DHAQ
  • Novantrone
Drug: cytarabine
Given IT or IV
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies
Other: questionnaire administration
Ancillary studies
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Experimental: Induction II, Arm B (LR patients)
Patients receive cytarabine IT, ADE chemotherapy, and bortezomib as in Induction I Arm B.
Drug: daunorubicin hydrochloride
Given IV
Other Names:
  • Cerubidin
  • Cerubidine
  • daunomycin hydrochloride
  • daunorubicin
  • RP-13057
Drug: cytarabine
Given IT or IV
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Drug: bortezomib
Given IV
Other Names:
  • LDP 341
  • MLN341
  • VELCADE
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies
Other: questionnaire administration
Ancillary studies
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Experimental: Induction II, Arm B (HR patients)
Patients receive MA chemotherapy as in Induction II, Arm A (HR patients) and bortezomib IV on days 1, 4, and 8.
Drug: daunorubicin hydrochloride
Given IV
Other Names:
  • Cerubidin
  • Cerubidine
  • daunomycin hydrochloride
  • daunorubicin
  • RP-13057
Drug: mitoxantrone hydrochloride
Given IV
Other Names:
  • CL 232315
  • DHAD
  • DHAQ
  • Novantrone
Drug: cytarabine
Given IT or IV
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Drug: bortezomib
Given IV
Other Names:
  • LDP 341
  • MLN341
  • VELCADE
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies
Other: questionnaire administration
Ancillary studies
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Experimental: Induction II, Arm C

Patients receive cytarabine IT on day 1, cytarabine IV over 1-30 minutes on days 1-8, daunorubicin IV over 1-15 minutes on days 1, 3, and 5, and etoposide IV over 1-2 hours on days 1-5, and sorafenib tosylate PO on days 1-28.

Maintenance: Patients receive sorafenib tosylate PO starting on day 40-80 after completion of intensification II or SCT for one year.

Drug: daunorubicin hydrochloride
Given IV
Other Names:
  • Cerubidin
  • Cerubidine
  • daunomycin hydrochloride
  • daunorubicin
  • RP-13057
Drug: sorafenib tosylate
Given PO
Other Names:
  • BAY 43-9006
  • BAY 43-9006 Tosylate Salt
  • BAY 54-9085
  • Nexavar
  • SFN
Drug: cytarabine
Given IT or IV
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies
Other: questionnaire administration
Ancillary studies
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Experimental: Intensification I, Arm A
Patients receive cytarabine IT on day 1 and AE chemotherapy comprising high-dose cytarabine IV over 1-3 hours, and etoposide IV over 1-2 hours on days 1-5.
Drug: cytarabine
Given IT or IV
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies
Other: questionnaire administration
Ancillary studies
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Experimental: Intensification I, Arm B
Patients receive cytarabine IT and AE chemotherapy in Intensification II, Arm A, and bortezomib IV on days 1, 4, and 8.
Drug: cytarabine
Given IT or IV
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Drug: bortezomib
Given IV
Other Names:
  • LDP 341
  • MLN341
  • VELCADE
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Experimental: Intensification I, Arm C
Patients receive cytarabine IT and AE chemotherapy in Intensification II, Arm A, and sorafenib tosylate PO on daily on days 1-28.
Drug: daunorubicin hydrochloride
Given IV
Other Names:
  • Cerubidin
  • Cerubidine
  • daunomycin hydrochloride
  • daunorubicin
  • RP-13057
Drug: sorafenib tosylate
Given PO
Other Names:
  • BAY 43-9006
  • BAY 43-9006 Tosylate Salt
  • BAY 54-9085
  • Nexavar
  • SFN
Drug: cytarabine
Given IT or IV
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies
Other: questionnaire administration
Ancillary studies
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Experimental: Intensification II, Arm A (LR)
Patients receive cytarabine IT on day 1 and MA chemotherapy as in Induction II, Arm A (HR patients).
Drug: daunorubicin hydrochloride
Given IV
Other Names:
  • Cerubidin
  • Cerubidine
  • daunomycin hydrochloride
  • daunorubicin
  • RP-13057
Drug: cytarabine
Given IT or IV
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies
Other: questionnaire administration
Ancillary studies
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Experimental: Intensification II, Arm B (LR)
Patients receive cytarabine IT on day 1, MA chemotherapy as in Induction II, Arm A (HR patients), and bortezomib IV on days 1, 4, and 8.
Drug: daunorubicin hydrochloride
Given IV
Other Names:
  • Cerubidin
  • Cerubidine
  • daunomycin hydrochloride
  • daunorubicin
  • RP-13057
Drug: cytarabine
Given IT or IV
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Drug: bortezomib
Given IV
Other Names:
  • LDP 341
  • MLN341
  • VELCADE
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies
Other: questionnaire administration
Ancillary studies
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Experimental: Intensification II, Arms A and B
Patients receive high-dose cytarabine IV over 3 hours on days 1, 2, 8, and 9 and asparaginase IM on days 2 and 9.
Drug: asparaginase
Given IM
Other Names:
  • ASNase
  • Colaspase
  • Crasnitin
  • Elspar
  • L-ASP
Drug: cytarabine
Given IT or IV
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies
Other: questionnaire administration
Ancillary studies
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Experimental: Intensification II, Arm C
Patients receive cytarabine IT on day 1, MA chemotherapy as in Induction II, Arm A (HR patients), and sorafenib tosylate PO on days 1-28.
Drug: daunorubicin hydrochloride
Given IV
Other Names:
  • Cerubidin
  • Cerubidine
  • daunomycin hydrochloride
  • daunorubicin
  • RP-13057
Drug: sorafenib tosylate
Given PO
Other Names:
  • BAY 43-9006
  • BAY 43-9006 Tosylate Salt
  • BAY 54-9085
  • Nexavar
  • SFN
Drug: cytarabine
Given IT or IV
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies
Other: questionnaire administration
Ancillary studies
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 29 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
    • 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 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 intrathecal (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
  • All patients and/or their parents or legal guardians must sign a written informed consent
  • All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01371981

  Show 186 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Richard Aplenc Children's Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01371981     History of Changes
Other Study ID Numbers: NCI-2011-02670, NCI-2011-02670, COG-AAML1031, CDR0000701850, AAML1031, AAML1031, U10CA098543
Study First Received: June 10, 2011
Last Updated: December 16, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Congenital Abnormalities
Neoplasms
Leukemia
Leukemia, Erythroblastic, Acute
Leukemia, Megakaryoblastic, Acute
Leukemia, Monocytic, Acute
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Leukemia, Myelomonocytic, Acute
Leukemia, Myelomonocytic, Chronic
Neoplasms by Histologic Type
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Myelodysplastic-Myeloproliferative Diseases
Etoposide phosphate
Bortezomib
Sorafenib
Asparaginase
Cytarabine
Daunorubicin
Etoposide
Mitoxantrone
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents

ClinicalTrials.gov processed this record on April 22, 2014