Overview

This trial is active, not recruiting.

Conditions acute myeloid leukemia arising from previous myelodysplastic syndrome, adult acute megakaryoblastic leukemia, adult acute monoblastic leukemia, adult acute monocytic leukemia, adult acute myeloid leukemia with minimal differentiation, adult acute myeloid leukemia with t(9;11)(p22;q23); mllt3-mll, adult acute myeloid leukemia without maturation, adult erythroleukemia, adult pure erythroid leukemia, alkylating agent-related acute myeloid leukemia, secondary acute myeloid leukemia, untreated adult acute myeloid leukemia
Treatments bortezomib, decitabine, laboratory biomarker analysis, pharmacological study, quality-of-life assessment, questionnaire administration
Phase phase 2
Target proteasome
Sponsor National Cancer Institute (NCI)
Start date November 2011
End date June 2015
Trial size 165 participants
Trial identifier NCT01420926, CALGB 11002, CALGB-11002, CDR0000709218, NCI-2011-02987, U10CA031946, U10CA180821

Summary

This randomized phase II trial studies how well giving decitabine with or without bortezomib works in treating older patients with acute myeloid leukemia. Drugs used in chemotherapy, such as decitabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. It is not yet known whether decitabine works better when given with or without bortezomib in treating acute myeloid leukemia.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
REMISSION INDUCTION THERAPY: Patients receive 20 mg/m^2 decitabine IV over 1 hour QD on days 1-10. Treatment repeats every 28 days for 2-4 courses in the absence of disease progression or unacceptable toxicity. Patients not achieving CR or CRi proceed to continuation therapy. Patients achieving CR or CRi proceed to maintenance therapy. CONTINUATION THERAPY: Patients receive 20 mg/m^2 decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive 20 mg/m^2 decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
decitabine 5-Aza-2'-deoxycytidine
Given IV
laboratory biomarker analysis
Correlative studies
pharmacological study
Correlative studies
quality-of-life assessment Quality of Life Assessment
Ancillary studies
questionnaire administration
Ancillary studies
(Experimental)
REMISSION INDUCTION THERAPY: Patients receive 20 mg/m^2 decitabine IV over 1 hour QD on days 2-11 and 1.3 mg/m^2 bortezomib SC on days 1, 4, 8, and 11. Treatment repeats every 28 days for 2-4 courses in the absence of disease progression or unacceptable toxicity. Patients not achieving CR or CRi proceed to continuation therapy. Patients achieving CR or CRi proceed to maintenance therapy. CONTINUATION THERAPY: Patients receive 1.3 mg/m^2 bortezomib SC on day 1 and 20 mg/m^2 decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive 1.3 mg/m^2 bortezomib SC on day 1 and 20 mg/m^2 decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
bortezomib [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid
Given SC
decitabine 5-Aza-2'-deoxycytidine
Given IV
laboratory biomarker analysis
Correlative studies
pharmacological study
Correlative studies
quality-of-life assessment Quality of Life Assessment
Ancillary studies
questionnaire administration
Ancillary studies

Primary Outcomes

Measure
Overall survival (OS) time
time frame: Time from study entry to death assessed up to 10 years

Secondary Outcomes

Measure
Complete remission rate (CR and CRi)
time frame: Duration of study up to 10 years
Disease-free survival (DFS)
time frame: Time from study entry to relapse and/or death (up to 10 years)
Progression-free survival
time frame: Time from study entry to progression and/or death (up to 10 years)

Eligibility Criteria

Male or female participants at least 60 years old.

Inclusion Criteria: - Unequivocal pathologic diagnosis of AML (>= 20% blasts in the bone marrow based on World Health Organization [WHO] criteria) EXCLUDING: - Acute promyelocytic leukemia t(15;17)(q22;q12); promyelocytic leukemia (PML)-retinoic acid receptor, alpha (RARA) - Acute myeloid leukemia with t(8;21)(q22;q22); runt-related transcription factor 1 (RUNX1)-runt-related transcription factor 1; translocated to, 1 (RUNXT1) as determined by the Ohio State University (OSU) Molecular Reference Laboratory, per Cancer and Leukemia Group B (CALGB) 20202; however patients who (1) are >= 75 years; and/or (2) have an ejection fraction of < 40%; and/or (3) have a performance status of > 2, may be registered to CALGB 20202 and registered and treated on CALGB 11002 prior to receiving the fms-related tyrosine kinase 3 (FLT3) mutation and core-binding factor (CBF) molecular screening results from CALGB 20202 - Acute myeloid leukemia with inv(16)(p13.1;q22) or t(16;16)(p13.1;q22); core-binding factor, beta subunit (CBFB)-myosin, heavy chain 11, smooth muscle (MYH11) as determined by the OSU Molecular Reference Laboratory, per CALGB 20202; however patients who (1) are >= 75 years; and/or (2) have an ejection fraction of < 40%; and/or (3) have a performance status of > 2, may be registered to CALGB 20202 and registered and treated on CALGB 11002 prior to receiving the FLT3 mutation and CBF molecular screening results from CALGB 20202 - Absence of FLT3 mutation (internal tandem duplication [ITD] or point mutation) determined by the OSU Molecular Reference Laboratory, per CALGB 20202; however patients who (1) are >= 75 years; and/or (2) have an ejection fraction of < 40%; and/or (3) have a performance status of > 2, may be registered to CALGB 20202 and registered and treated on CALGB 11002 prior to receiving the FLT3 mutation and CBF molecular screening results from CALGB 20202 - No prior treatment for AML except: - Emergency leukapheresis - Emergency treatment for hyperleukocytosis with hydroxyurea - Cranial radiotherapy (RT) for central nervous system (CNS) leukostasis (one dose only) - Growth factor/cytokine support - AML patients with an antecedent hematologic disorder (AHD) or myelodysplastic syndrome (MDS) are eligible for this trial provided that they have not received treatment for their AHD or MDS with cytotoxic chemotherapy (e.g., cytarabine, daunorubicin, etc.), decitabine, or bortezomib; patients may have been previously treated with azacitidine if their last dose was >= 90 days prior to starting 11002 - AML patients with therapy-related myeloid neoplasms (t-MN) are eligible if they have not received radiation therapy or chemotherapy (not including hormonal therapy) for their primary malignancy or disorder for > 6 months

Additional Information

Official title A Randomized Phase II Trial of Decitabine-Based Induction Strategies for Patients ≥ 60 Years Old With Acute Myeloid Leukemia (AML)
Principal investigator Gail Roboz
Description PRIMARY OBJECTIVE: I. To determine if treatment of older acute myeloid leukemia (AML) patients with decitabine and bortezomib significantly improves the overall survival times of older AML patients compared with decitabine alone. SECONDARY OBJECTIVES: I. To determine the rate of complete remission (CR and CR + incomplete blood count recovery [CRi]) for each of the 2 treatment regimens in the proposal. II. To determine the overall survival, progression-free survival, disease-free survival and for each of the treatment regimens on this study. III. To determine whether ongoing treatment with these regimens prolongs overall survival even in the absence of complete remission. IV. To describe the frequency and severity of adverse events, as well as the tolerability of each of these regimens in patients treated on this study. V. To describe the interaction of pretreatment disease and patient characteristics including morphology, cytogenetics, molecular genetics, white blood cell (WBC) count, blood and bone marrow blast count, age, performance status and comprehensive geriatric assessment on clinical outcomes. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: REMISSION INDUCTION THERAPY: Patients receive decitabine intravenously (IV) over 1 hour once daily (QD) on days 1-10. Treatment repeats every 28 days for 2-4 courses in the absence of disease progression or unacceptable toxicity. Patients not achieving CR or CR with CRi proceed to continuation therapy. Patients achieving CR or CR with CRi proceed to maintenance therapy. CONTINUATION THERAPY: Patients receive decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. ARM II: REMISSION INDUCTION THERAPY: Patients receive decitabine IV over 1 hour QD on days 2-11 and bortezomib subcutaneously (SC) on days 1, 4, 8, and 11. Treatment repeats every 28 days for 2-4 courses in the absence of disease progression or unacceptable toxicity. Patients not achieving CR or CRi proceed to continuation therapy. Patients achieving CR or CR with CRi proceed to maintenance therapy. CONTINUATION THERAPY: Patients receive bortezomib SC on day 1 and decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive bortezomib SC on day 1 and decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 2 months for 2 years, every 3 months for 2 years, and then once a year for 6 years.
Trial information was received from ClinicalTrials.gov and was last updated in March 2016.
Information provided to ClinicalTrials.gov by National Cancer Institute (NCI).