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Anti-Infective Agents

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Cytarabine

Antimetabolites

Antiviral Agents

Immunosuppressive Agents

Immunologic Factors

Dose-escalation Phase

* Schedule A:
* Schedule B:

Expansion Phase

* Schedule A:
* Schedule B:

Dose-escalation Phase

* Schedule A: vosaroxin injection (dose-escalation from 10 to 90 mg/m2) on Days 1 and 4 in combination with cytarabine (24-hour CIV infusion of 400 mg/m2/day × 5 days)
* Schedule B: vosaroxin injection (dose-escalation from 70 to 90 mg/m2) on Days 1 and 4 in combination with cytarabine (2-hour intravenous \[IV\] infusion of 1 g/m2/day × 5 days)

Expansion Phase The MTD determined in the dose-escalation phase was used in the expansion phase.

* Schedule A: 80 mg/m2 vosaroxin on Days 1 and 4 in combination with cytarabine (24-hour CIV infusion at 400 mg/m2/day × 5 days)
* Schedule B: 90 mg/m2 vosaroxin (dose-escalation) on Days 1 and 4 in combination with cytarabine (2 hour IV infusion at 1 g/m2/day × 5 days)

Voreloxin injection and cytarabine

Sunesis Medical Monitor, MD

This study will evaluate the safety and tolerability of voreloxin (vosaroxin) injection in combination with cytarabine in patients with relapsed or refractory acute myeloid leukemia.

An open-label, Phase 1b/2 study using a dose-escalation design with expansion at the maximum tolerated dose (MTD) using 2 dosing schedules:

During the Schedule A dose-escalation phase, patients with relapsed or refractory acute myeloid leukemia (AML) enrolled in cohorts of at least 3 patients to identify the MTD. Begin with a starting dosing regimen of vosaroxin of 10 mg/m2 on Days 1 and 4 of each cycle in combination with a 24-hour continuous intravenous (CIV) infusion of cytarabine 400 mg/m2/day × 5 days. If none of the 3 patients or 1 of 6 patients experience a dose-limiting toxicity (DLT) at the vosaroxin starting dose, dose-escalate vosaroxin. If 2 of 6 patients experienced a DLT at the vosaroxin starting dose, reduce the dose of cytarabine to reduced to 200 mg/m2 (only case in which the cytarabine could have been reduced). The vosaroxin dose escalated following a modified Fibonacci schema.

For Schedule B dose-escalation phase, patients with relapsed or refractory AML enrolled in cohorts of at least 3 patients to identify the MTD. Begin with a starting dose regimen of vosaroxin of 70 mg/m2 on Days 1 and 4 in combination with cytarabine as a 2-hour infusion of 1 g/m2/day × 5 days. No reductions of cytarabine allowed in Schedule B. If none of the 3 patients or 1 of 6 patients experienced a DLT in the first cohort of Schedule B, escalate the dose of vosaroxin. If DLTs occurred in 2 of 6 patients during the starting dose, reduce the vosaroxin dose to 50 mg/m2.

For both Schedules, the highest dose at which fewer than 2 of 6 patients experienced a DLT during induction became the MTD and the recommended future dose.

Once the MTD of vosaroxin was determined for Schedule A, first relapse patients were enrolled in the expansion phase at that dose level to obtain additional safety and efficacy information. When the MTD of vosaroxin was determined for Schedule B, first relapse patients and patients with primary refractory disease were enrolled in the expansion phase at that dose level to characterize the safety and efficacy profile in this population.

Safety and Tolerability Study of Voreloxin and Cytarabine Combination in Acute Myeloid Leukemia in Humans

Phase 1b/2, Open-Label, Multicenter, Dose-Escalating, Clinical Study of the Safety, Tolerability, and PK and PD Profiles of Voreloxin Injection in Combination With Cytarabine in Patients With Relapsed or Refractory AML

Patients were treated in cohorts with escalating doses of vosaroxin administered in combination with cytarabine in Schedule A, and with vosaroxin in escalating doses in Schedule B. For both Schedules, the highest dose at which fewer than 2 of 6 (\<0.33) patients experienced a dose-limiting toxicity (DLT) during induction became the MTD and the recommended future dose.

Complete remission (CR) plus CR with incomplete platelet recovery (CRp) per The IWG criteria for remission modified by Sunesis, assessed by investigator.

CR is defined as \>1000 Neutrophils (ul), \>100,000 Platelets (uL) and \<5 BM Blasts (%); CRp is defined as \>1000 Neutrophils (ul), \<=100,000 Platelets (uL) and \<5 BM Blasts (%); CRi is defined as \>1000 Neutrophils (ul), \<100,000 Platelets (uL) and \<5 BM Blasts (%); Investigators were to determine a response category for each patient by examination of bone marrow and blood counts at the time of hematologic recovery after induction or reinduction. Investigator assessment categories included CR, CRp, CRi (CR with morphologic CR with incomplete blood count recovery), PR (partial remission), treatment failure, and relapse.

Leukemia-free survival is censored at the last known alive date without report of relapse.

Overall survival is censored at the earlier of the cutoff date for analysis and the last date known to be alive for patients not known to have died.

Mortality of those patients enrolled in the study and receiving intervention

Sunesis Pharmaceuticals

Schedule A: vosaroxin injection (dose-escalation from 10 to 90 mg/m2) on Days 1 and 4 in combination with cytarabine (24-hour continuous IV \[CIV\] infusion of 400 mg/m2/day × 5 days)

Group 1 (Sch A, 10 to 90 mg/m2):

saroxin injection (dose-escalation from 70 to 90 mg/m2) on Days 1 and 4 in combination with cytarabine (2-hour intravenous \[IV\] infusion of 1 g/m2/day × 5 days)

Group 2 (Sch B, 70 to 90 mg/m2):

Group 3 (Sch A, First Relapse, 80 mg/m2)

Schedule B: vosaroxin injection (dose-escalation from 70 to 90 mg/m2) on Days 1 and 4 in combination with cytarabine (2-hour intravenous \[IV\] infusion of 1 g/m2/day × 5 days)

Group 4 (Sch B, First Relapse, 90 mg/m2):

Group 5 (Sch B, Primary Refractory, 90 mg/m2):

Group 1 (Sch A, 10 to 90 mg/m2)

Group 3 (Sch A, First Relapse, 80 mg/m2):

Group 4 (Sch B, First Relapse, 90 mg/m2)

Total

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Further study is needed to confirm the results due to limited sampling size. Statistical fields are not included here because no statistical testings were performed to compare any of the treatment groups. No p-values or odds ratios were reported.

Mike Johnston, Senior Director Regulatory Affairs

Vosaroxin injection 10 mg/m2 on Days 1 and 4 in combination with cytarabine (24-hour continuous IV \[CIV\] infusion of 400 mg/m2/day × 5 days)

Sch A, Cohort 10mg/m2

Vosaroxin injection 20 mg/m2 on Days 1 and 4 in combination with cytarabine (24-hour continuous IV \[CIV\] infusion of 400 mg/m2/day × 5 days)

Sch A, Cohort 20mg/m2

Vosaroxin injection 34 mg/m2 on Days 1 and 4 in combination with cytarabine (24-hour continuous IV \[CIV\] infusion of 400 mg/m2/day × 5 days)

SchA, Cohort 34mg/m2

Vosaroxin injection 50 mg/m2 on Days 1 and 4 in combination with cytarabine (24-hour continuous IV \[CIV\] infusion of 400 mg/m2/day × 5 days)

Sch A, Cohort 50mg/m2

Vosaroxin injection 70 mg/m2 on Days 1 and 4 in combination with cytarabine (24-hour continuous IV \[CIV\] infusion of 400 mg/m2/day × 5 days)

Sch A, Cohort 70mg/m2

Vosaroxin injection 80 mg/m2 on Days 1 and 4 in combination with cytarabine (24-hour continuous IV \[CIV\] infusion of 400 mg/m2/day × 5 days)

Sch A, Cohort 80mg/m2

Vosaroxin injection 90 mg/m2 on Days 1 and 4 in combination with cytarabine (24-hour continuous IV \[CIV\] infusion of 400 mg/m2/day × 5 days)

Sch A, Cohort 90mg/m2

Schedule B: vosaroxin injection 70 mg/m2 on Days 1 and 4 in combination with cytarabine (2-hour intravenous \[IV\] infusion of 1 g/m2/day × 5 days).

Sch B, Cohort 70 mg/m2

Sch B, Cohort 80mg/m2

Sch B, Cohort 90mg/m2

Patients experiencing a dose-limiting toxicity (DLT) during induction when treated with escalating doses of vosaroxin administered in combination with cytarabine on Days 1 and 4 in Schedule A, and with vosaroxin in escalating doses administered on Days 1 and 4 in Schedule B.

Incidence of Dose-Limiting Toxicity (DLT) to Determine Maximum Tolerated Dose in Schedule A and Schedule B of Dose Escalation Phase (Group 1 and Group 2)

All treated set which includes all enrolled patients who received any IMP.

Remission Rates (CR+CRp)

Leukemia-free Survival (LFS)

Overall Survival

30 Days

60 Days

Dose Escalation Phase Schedule A: vosaroxin injection (dose-escalation from 10 to 90 mg/m2) on Days 1 and 4 in combination with cytarabine (24-hour continuous IV \[CIV\] infusion of 400 mg/m2/day × 5 days)

Dose Escalation Phase Schedule B: vosaroxin injection (dose-escalation from 70 to 90 mg/m2) on Days 1 and 4 in combination with cytarabine (2-hour intravenous \[IV\] infusion of 1 g/m2/day × 5 days)

Expansion Phase: Schedule A: 80 mg/m2 vosaroxin on Days 1 and 4 in combination with cytarabine (24-hour CIV infusion at 400 mg/m2/day × 5 days)

Expansion Phase: Schedule B: 90 mg/m2 vosaroxin (dose-escalation) on Days 1 and 4 in combination with cytarabine (2 hour IV infusion at 1 g/m2/day × 5 days)

Expansion Phase Schedule B: 90 mg/m2 vosaroxin (dose-escalation) on Days 1 and 4 in combination with cytarabine (2 hour IV infusion at 1 g/m2/day × 5 days)

Spots Global Cancer Trial Database for voreloxin injection and cytarabine