Trial Information

Dose Escalation and Phase II Study of Bortezomib (IND #58443, NSC # 681239) Added to Standard Daunorubicin and Cytarabine Therapy for Patients With Previously Untreated Acute Myeloid Leukemia Age 60-75 Years

PRIMARY OBJECTIVES:

I. To define the remission induction response rate (complete response [CR] and CR with
incomplete platelet recovery [CRp]) in older patients with previously untreated acute
myeloid leukemia treated with induction therapy comprising bortezomib in combination with
daunorubicin hydrochloride and cytarabine.

II. To define the maximum tolerated dose of bortezomib when administered in combination with
intermediate-dose cytarabine after induction therapy.

SECONDARY OBJECTIVES:

I. To describe the disease-free survival of patients treated with this regimen.

II. To describe the overall survival of patients treated with this regimen.

III. To evaluate the treatment-related toxicities in these patients.

OUTLINE: This is a multicenter, dose-escalation study of bortezomib. Doses of bortezomib are
escalated during remission consolidation therapy.

- Remission induction therapy:

- Remission induction course 1: Patients receive bortezomib IV over 3-5 seconds on
days 1, 4, 8, and 11; daunorubicin hydrochloride IV on days 1-3; and cytarabine IV
continuously over 168 hours on days 1-7.

After completion of remission induction course 1, patients undergo bone marrow aspiration
and biopsy for evaluation of response. Patients achieving a complete response (CR) or
partial response (PR) proceed to remission consolidation therapy. Patients achieving a CR
with incomplete platelet recovery (CRp) proceed to remission consolidation therapy after
platelet counts recover. Patients with persistent leukemia (≥ 20% bone marrow cellularity
and ≥ 5% bone marrow myeloblasts) proceed to remission induction course 2.

- Remission induction course 2: Patients receive bortezomib IV over 3-5 seconds on days 1
and 4; daunorubicin hydrochloride IV on days 1 and 2; and cytarabine IV continuously
over 120 hours on days 1-5.

After completion of remission induction course 2, patients undergo bone marrow aspiration
and biopsy for evaluation of response. Patients achieving a CR or PR proceed to remission
consolidation therapy. Patients achieving a CRp proceed to remission consolidation therapy
after platelet counts recover. Patients with residual leukemia who do not meet the criteria
for PR are removed from the study.

- Remission consolidation therapy: Patients receive bortezomib IV over 3-5 seconds on
days 1, 4, 8, and 11 and intermediate-dose cytarabine IV over 3 hours on days 1-5.
Patients then undergo bone marrow aspiration and biopsy for evaluation of response.
Patients achieving a CR or who demonstrate continuing CR receive a second course of
remission consolidation therapy beginning 2-4 weeks after blood counts recover.

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