Trial record 1 of 1 for:    NCT01420926
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Decitabine With or Without Bortezomib in Treating Older Patients With Acute Myeloid Leukemia

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01420926
First received: August 19, 2011
Last updated: March 14, 2016
Last verified: January 2016

August 19, 2011
March 14, 2016
November 2011
June 2015   (final data collection date for primary outcome measure)
Overall survival (OS) time [ Time Frame: Time from study entry to death assessed up to 10 years ] [ Designated as safety issue: No ]
Overall survival (OS) was defined as the time from study entry to death of any cause. Surviving patients were censored at the date of last follow-up. The median OS with 95% CI was estimated using the Kaplan Meier method.
Overall survival time [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01420926 on ClinicalTrials.gov Archive Site
  • Complete remission rate (CR and CRi) [ Time Frame: Duration of study up to 10 years ] [ Designated as safety issue: No ]
    Defined as the number of patients who achieve a CR or CRi divided by the total number of evaluable patients. A Complete remission (CR) requires: <5% marrow blast, > 200 nucleated cells, no blasts with auer rods, no extramedullary disease, ANC >1,000/mm^3 and platelets > 100,000/mm^3. A CR with incomplete blood count recovery (CRi) is defined as CR with exception of ANC < 1,000/mm^3 or platelets < 100,000/mm^3.
  • Disease-free survival (DFS) [ Time Frame: Time from study entry to relapse and/or death (up to 10 years) ] [ Designated as safety issue: No ]
    Disease free survival (DFS) was defined as the time from CR to relapse or death. Relapse free and surviving patients were censored at the date of last follow-up. The median DFS with 95% CI was estimated using the Kaplan Meier method. Relapse is defined as the reappearance of blood blasts or >= 5% marrow blasts after achieving a CR or CRi.
  • Progression-free survival [ Time Frame: Time from study entry to progression and/or death (up to 10 years) ] [ Designated as safety issue: No ]
    Progression free survival (PFS) was defined as the time from study entry to progression or death. Progression free and surviving patients were censored at the date of last follow-up. The median DFS with 95% CI was estimated using the Kaplan Meier method.
  • Complete remission rate (CR and CRi) [ Designated as safety issue: No ]
  • Overall survival, progression-free survival, disease-free survival, and remission duration [ Designated as safety issue: No ]
  • Frequency and severity of adverse events [ Designated as safety issue: Yes ]
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Decitabine With or Without Bortezomib in Treating Older Patients With Acute Myeloid Leukemia
A Randomized Phase II Trial of Decitabine-Based Induction Strategies for Patients ≥ 60 Years Old With Acute Myeloid Leukemia (AML)
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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • 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
  • Drug: Bortezomib
    Given SC
    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: Decitabine
    Given IV
    Other Names:
    • 5-Aza-2'-deoxycytidine
    • Dacogen
    • Decitabine for Injection
    • Deoxyazacytidine
    • Dezocitidine
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Other: Pharmacological Study
    Correlative studies
  • Other: Quality-of-Life Assessment
    Ancillary studies
    Other Name: Quality of Life Assessment
  • Other: Questionnaire Administration
    Ancillary studies
  • Experimental: Arm I (decitabine)

    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.

    Interventions:
    • Drug: Decitabine
    • Other: Laboratory Biomarker Analysis
    • Other: Pharmacological Study
    • Other: Quality-of-Life Assessment
    • Other: Questionnaire Administration
  • Experimental: Arm II (decitabine and bortezomib)

    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.

    Interventions:
    • Drug: Bortezomib
    • Drug: Decitabine
    • Other: Laboratory Biomarker Analysis
    • Other: Pharmacological Study
    • Other: Quality-of-Life Assessment
    • Other: Questionnaire Administration
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
165
Not Provided
June 2015   (final data collection date for primary outcome measure)

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
Both
60 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01420926
NCI-2011-02987, NCI-2011-02987, CDR0000709218, CALGB 11002, CALGB-11002, U10CA180821, U10CA031946
Not Provided
Not Provided
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Gail Roboz Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
January 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP