Trial Information

A Phase II Study Incorporating Sorafenib (IND 69896, NSC 724772) Into the Therapy of Patients >/= 60 Years of Age With FLT3 Mutated Acute Myeloid Leukemia

PRIMARY OBJECTIVES:

I. To determine if the 1-year overall survival rate of patients age >= 60 with internal
tandem duplications of fms-like tyrosine kinase (FLT3-ITD) AML treated with a sorafenib
(sorafenib tosylate) containing induction and post-remission therapy is significantly higher
than the historical 1-year overall survival rate of similar patients who were not treated
with sorafenib.

SECONDARY OBJECTIVES:

I. To determine the rates of complete remission (CR), CR with incomplete count recovery
(CRi), and cytogenetic complete remission (CCyR) to induction chemotherapy.

II. To determine the overall survival, event-free survival, and remission duration in
patients treated on this study.

III. To describe the frequency and severity of adverse events for patients treated on this
study.

IV. To describe the interaction of pre-treatment disease and patient characteristics
including morphology, cytogenetics, immunophenotype, molecular genetic features, white blood
cell (WBC) count and hemogram, and performance status on clinical outcomes.

V. To assess FLT3 ligand concentrations and FLT3 plasma inhibitory activity during treatment
and determine the relationship to clinical outcomes.

VI. To describe the interaction of FLT3 mutation type (tyrosine kinase domain [TKD] vs. ITD)
and allelic ratio on clinical outcomes.

VII. To characterize geriatric assessment measures in the context of a treatment trial for
AML defined by: the observed distribution and number of missing values for each measurement.

VIII. To identify specific geriatric assessment measures which are independently associated
with overall survival (OS), 30-day treatment-related mortality and key quality of life
outcomes (number of days hospitalized, number of oncology clinic visits, admission to a
nursing facility) in patients receiving induction chemotherapy for AML.

IX. To explore the impact of induction chemotherapy on physical, cognitive, psychosocial
factors.

OUTLINE: This is a multicenter study.

INDUCTION THERAPY: Patients receive daunorubicin hydrochloride intravenously (IV) on days
1-3, cytarabine IV continuously on days 1-7, and sorafenib tosylate orally (PO) twice daily
on days 1-7. Patients then undergo a bone marrow aspirate or biopsy on day 14.

Patients with persistent disease undergo a second remission induction therapy comprising
daunorubicin hydrochloride IV on days 1-2, cytarabine IV continuously on days 1-5, and
sorafenib tosylate PO twice daily on days 1-7. Patients who achieve complete response (CR)*
proceed to consolidation therapy.

CONSOLIDATION THERAPY: Patients** receive cytarabine IV over 3 hours on days 1-5 and
sorafenib tosylate PO twice daily on days 1-28. Treatment repeats every 28 days for 2
courses in the absence of disease progression or unacceptable toxicity. Patients with
continued CR proceed to maintenance therapy.

MAINTENANCE THERAPY: Patients receive sorafenib tosylate PO twice daily on days 1-28.
Treatment repeats every 28 days for up to 12 courses in the absence of disease progression
or unacceptable toxicity.

NOTE: *Patients who achieve CR and who are eligible for hematopoietic stem cell
transplantation (HSCT) are encouraged to enroll in CALGB 100103. Patients in CR who are
unable or unwilling to undergo HSCT receive two courses of remission consolidation therapy.

NOTE: ** Patients in CR/complete remission with incomplete count recovery (CRi) who are
unable or unwilling to complete remission consolidation therapy may proceed directly to
maintenance therapy after consulting with the CALGB study chair.

Patients may undergo bone marrow aspirate, tumor biopsy, and/or blood sampling at baseline
and periodically during study for cytogenetic, biomarker, and mutation analysis.

After completion of study therapy, patients are followed up every 2 months for 2 years,
every 3 months for 2 years, and then yearly for at least 10 years.