Trial Information

A Phase III Randomized of Cloretazine™ (VNP40101M) and Cytosine Arabinoside (AraC) in Patients With Acute Myeloid Leukemia in First Relapse

OBJECTIVES:

Primary

- Compare the complete response (CR) and CR (with platelet count < 100,000/mm^3 but ≥
20,000/mm^3 [transfusion independent for ≥ 7 consecutive days]) (CRp) rates in patients
with acute myeloid leukemia in first relapse treated with cytarabine with vs without
VNP40101M.

Secondary

- Compare time to progression in patients treated with these regimens.

- Compare duration of response in patients treated with these regimens.

- Compare the survival of patients treated with these regimens.

- Compare the toxicity of these regimens in these patients.

OUTLINE: This is a randomized, double-blind, placebo-controlled, parallel group, multicenter
study. Patients are stratified according to age (< 60 years vs ≥ 60 years) and duration of
first complete response (CR) or CR (with platelet count < 100,000/mm³ but ≥ 20,000/mm³
[transfusion independent for ≥ 7 consecutive days]) (CRp) (< 12 months vs ≥ 12 months).

- Induction therapy: Patients are randomized to 1 of 2 treatment arms.

- Arm I: Patients receive cytarabine IV continuously on days 1-3 and VNP40101M IV
over 30-60 minutes on day 2 (at least 12 hours after the start of cytarabine).

- Arm II: Patients receive cytarabine as in arm I and placebo IV over 30-60 minutes
on day 2 (at least 12 hours after the start of cytarabine).

In both arms, patients demonstrating at least 20% reduction of blasts in bone marrow (based
on total cellularity and percent blasts) after course 1 may receive 1 additional course of
induction therapy between days 35-60 in the absence of disease progression or unacceptable
toxicity. Patients achieving CR or CRp after 1 or 2 courses of induction therapy proceed to
consolidation therapy.

- Consolidation therapy: Beginning 6 weeks after initial documentation of CR or CRp,
patients receive 1 course of consolidation therapy, as per induction therapy, according
to their randomized treatment arm. These patients may then proceed to other
consolidation, maintenance, and/or intensification therapy (including stem cell
transplantation) off study at the discretion of the physician.

After completion of study treatment, patients are followed monthly for 6 months, every 2
months for 6 months, and then every 3 months for 2 years.

PROJECTED ACCRUAL: A total of 420 patients (280 in arm I and 140 in arm II) will be accrued
for this study within 24-30 months.