Study of Vosaroxin or Placebo in Combination With Cytarabine in Patients With First Relapsed or Refractory AML

The study includes additional objectives to ones listed above as Outcome Measures. These
additional objectives also compared treatment groups in the following:

CR + CRp rate, defined as CR + CRp based on modified IWG response criteria.

Combined CR rate (CR+CRp+CRi).

Percentage of patients who have post-treatment (subsequent) transplantation.

Percentage of patients who received subsequent non-protocol therapy (including
transplantation).

Safety and tolerability.

In keeping with FDA guidance for adaptive trial designs, the study incorporated an
independent DSMB (Drug Safety Monitoring Board) to address potential uncertainty concerning
the true treatment affect between the treatment groups and to address a deterioration of
power from a small difference. Sunesis remained blinded and had no involvement in the interim
data analysis, interpretation, or adaptive design. Based on the results of the interim data
analysis the DSMB recommended an increase in the target number of deaths from 375 in 450
patients to 562 in 675 patients which based on a 5% dropout rate increased enrollment from
475 to 712.

The primary analysis was performed when the target number of deaths had been achieved based
on a permuted block randomization procedure, stratified by disease status (refractory, first
relapse with duration of first CR or CRp ≥ 90 days and < 12 months, or first relapse with
duration of first CR or CRp ≥ 12 months and ≤ 24 months), age (< 60 years or ≥ 60 years), and
geographic location (US or outside US). The study included periods of screening, treatment /
hematologic recovery, post-treatment follow-up, and long-term follow-up for survival.

Follow-up was monthly during the first year, every 2 months during the second year, and every
3 months thereafter until death, withdrawal of consent, or loss to follow-up, whichever
occurred first. Long-term follow-up began for all patients when the required number of deaths
for primary analysis had been met; thereafter, survival data were collected every 4 months
until death, withdrawal of consent, or loss to follow-up, whichever occurred first.

The long term follow-up for this study continues at this time and the September 2014 date
reflects database lock for primary analyses reflected in the Results Section. During long
term follow-up Sunesis is not collecting Adverse Events.

Inclusion Criteria:

- Provided signed, written informed consent

- At least 18 years of age

- Had a diagnosis of AML according to World Health Organization (WHO) classification

- First relapsed or refractory AML (refractory to initial induction therapy) with at
least 5% blasts by bone marrow or aspirate or 1% blasts in peripheral blood with
additional requirements for relapsed or refractory

- Had an ECOG score of 0-2

- Had adequate liver and renal function as indicated by certain laboratory values

- Had adequate cardiac function (left ventricular ejection fraction at least 40% by
multiple gated acquisition scan or ECG)

- Nonfertile or agreed to use an adequate method of contraception until 30 days after
the last treatment

- Had any clinically significant nonhematologic toxicity after prior chemotherapy
recovered to Grade 1 per NCI-CTCAE

Exclusion Criteria:

- Had acute promyelocytic leukemia

- Had more than 2 cycles of induction therapy for AML

- Had completed a single cycle of treatment containing a total dose of 5 g/m2 or more of
cytarabine within 90 days before randomization

- Refractory to or relapsed within the previous 3 months after therapy with an IDAC- or
HIDAC-containing regimen

- Had received a hematopoietic stem cell transplant (HSCT) within the previous 90 days

- Had received active immunosuppressive therapy for graft-versus-host disease (GVHD)
within 2 weeks before study start

- Had any other severe concurrent disease, or have a history of serious disease
involving the heart, kidney, liver, or other organ system

- Had evidence of central nervous system involvement of active AML

- Had other active malignancies (including other hematologic malignancies) or been
diagnosed with other malignancies within the last 12 months, except nonmelanoma skin
cancer or cervical intraepithelial neoplasia

- Had an active, uncontrolled infection

- Had received any other investigational therapy within 14 days or not recovered from
acute affects of the other investigational therapy

- Had received prior or current hydroxyurea or medications to reduce blast count within
24 hours before randomization

- Had received previous treatment with vosaroxin

- Pregnant or lactating

- Had any other medical, psychological, or social condition that may interfere with
consent, study participation, or follow-up

- Had known HIV seropositivity