Decitabine With or Without Bortezomib in Treating Older Patients With 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 A: 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 B: 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 a maximum of 10 years from study entry.

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); PML-RARA

- Acute myeloid leukemia with t(8;21)(q22;q22); RUNX1-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 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); CBFB-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 (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