Study of Vosaroxin or Placebo in Combination With Cytarabine in Patients With First Relapsed or Refractory Acute Myeloid Leukemia (AML) (VALOR)

This study will compare the overall survival (OS) between treatment groups of patients treated with vosaroxin and cytarabine versus patients treated with placebo and cytarabine.

Other objectives of this study include comparing the following between treatment groups:

Complete remission (CR) rate

Safety and tolerability

Combined CR rate, defined as CR+CRp+CRi

Overall remission (OR) rate

Event-free survival (EFS)

Durability of remission (CR and combined CR) assessed by leukemia-free survival (LFS)

Percentage of patients who have post-treatment transplantation

• Leukemia
• Acute Myeloid Leukemia
• Acute Nonlymphocytic Leukemia

• Drug: vosaroxin and cytarabine

  Vosaroxin days 1 and 4: 90 mg/m2 for induction 1; 70 mg/m2 for all other cycles

  Cytarabine 1 g/m2 daily on days 1-5 (IDAC)

• Drug: placebo and cytarabine

  Placebo days 1 and 4: volume matched to vosaroxin

  Cytarabine 1 g/m2 daily on days 1-5 (IDAC)

• Experimental: Group A: vosaroxin + cytarabine
  Vosaroxin will be administered in a blinded manner as a short IV infusion within 10 minutes on days 1 and 4 of each cycle (up to 4 cycles) and cytarabine will be administered in an unblinded manner as a 2-hour infusion on days 1-5 of each cycle.
  Intervention: Drug: vosaroxin and cytarabine
• Experimental: Group B: placebo + cytarabine
  Placebo will be administered in a blinded manner as a short IV infusion within 10 minutes on days 1 and 4 of each cycle (up to 4 cycles) and cytarabine will be administered in an unblinded manner as a 2-hour infusion on days 1-5 of each cycle.
  Intervention: Drug: placebo and cytarabine

Inclusion Criteria:

• Provide signed, written informed consent
• Are at least 18 years of age
• Have a diagnosis of AML according to World Health Organization (WHO) classification
• First relapsed or refractory AML (refractory to initial induction therapy)
• Have an ECOG score of 0-2
• Have adequate liver and renal function as indicated by certain laboratory values
• Are nonfertile or agree to use an adequate method of contraception until 30 days after the last treatment

Exclusion Criteria:

• Have received more than 2 cycles of induction therapy for AML
• Refractory to or relapsed within the previous 3 months after therapy with an IDAC- or HIDAC-containing regimen
• Have received a hematopoietic stem cell transplant (HSCT) within the previous 3 months
• Have received active immunosuppressive therapy for graft-versus-host disease (GVHD) within 2 weeks before study start
• Have any other severe concurrent disease, or have a history of serious disease involving the heart, kidney, liver, or other organ system
• Have evidence of central nervous system involvement of active AML
• Have 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
• Have an active, uncontrolled infection
• Are receiving any other investigational therapy
• Have received previous treatment with vosaroxin
• Are pregnant or lactating
• Have any other medical, psychological, or social condition that may interfere with consent, study participation, or follow-up