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Myeloid Leukemia

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* Schedule A: 72 mg/m2 vosaroxin Days 1, 8 and 15
* Schedule B: 72 mg/m2 vosaroxin on Days 1 and 8
* Schedule C: 72 mg/m2 on Days 1 and 4, or
* Schedule C: 90 mg/m2 on Days 1 and 4

Vosaroxin was administered by slow intravenous (IV) infusion or via syringe pump within 10 minutes.Patients could have completed up to 4 treatment cycles consisting of 1 or 2 induction treatment cycles and up to 2 consolidation treatment cycles. For Schedule A, an induction cycle was a minimum of 21 days during which patients received vosaroxin on Days 1, 8, and 15, followed by weekly observations until hematologic recovery for patients with aplastic marrow after the postinduction bone marrow assessment. For Schedules B and C, an induction cycle was a minimum of 15 days, during which patients received vosaroxin on Days 1 and 8 (Schedule B), or Days 1 and 4 (Schedule C), followed by the same weekly observations until hematologic recovery as for Schedule A.

vosaroxin

Adam Craig, MD

This study will evaluate the overall remission rate of treatment with vosaroxin (formerly voreloxin) Injection in patients at least 60 years of age with previously untreated AML

Other objectives of this study include:

1. Assess the safety of treatment with vosaroxin, including the 30 and 60 day all-cause mortality
2. Assess leukemia free survival (LFS), event-free survival (EFS), overall survival (OS), and duration of remission (DR).
3. Characterize the pharmacokinetic (PK) profile of vosaroxin in this patient population.
4. Evaluate potential stratification biomarkers by evaluating DNA-damage and apoptotic pathways in bone marrow samples before and after treatment with vosaroxin

Study of Voreloxin (Vosaroxin) in Older Patients With Untreated Acute Myeloid Leukemia

A Phase 2, Open-Label, Multicenter Clinical Study of the Safety and Efficacy of Voreloxin (Vosaroxin) Injection in Patients Equal to or Greater Than 60 Years of Age With Previously Untreated Acute Myeloid Leukemia

De-identified data of individual participants experiencing Serious Adverse Events

Combined remission rate (complete remission \[CR\] + complete remission with incomplete platelet recovery \[CRp\]) of vosaroxin of patients ≥ 60 years old with previously untreated (de novo or secondary) AML are presented by treatment group for all treated analysis set.

Per IWG criteria, a CR requires bone marrow blasts \< 5%, absolute neutrophil count (ANC) \> 1000 cells/uL, and platelet (plt) count \> 100,000 plt/uL. The criteria for CRp are the same as those for CR, except for platelet count \<= 100,000 lt/uL. 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 (Morphologic CR with incomplete blood count recovery), PR (partial remission), treatment failure, and relapse.

The censor date was the last known alive date without report of relapse.

Pharmacokinetic Parameters (Cmax) by Schedule, Dosing Day, and Dose Cohort for Patients Treated With Vosaroxin as a Single Agent (SPO 0014) for Day 1

Numbers reported are N, mean and CV%. Please note CV% is not a choice that can be entered from the drop down menu. The standard deviation is really CV% in the table.

Pharmacokinetic Parameters by Schedule, Dosing Day, and Dose Cohort for Patients Treated With Vosaroxin as a Single Agent (SPO 0014) on Day 4

Please note that N, mean and CV% are reported, but CV% is not an option in the drop down menu. So Standard Deviation is really CV% in the table.

Mortality of those patients enrolled in the study and receiving intervention

Pharmacokinetic Parameters (AUC0-72 and AUCinf ) by Schedule, Dosing Day, and Dose Cohort for Patients Treated With Vosaroxin as a Single Agent (SPO 0014) for Day 1

Numbers reported are N, mean and CV%. Please note CV% is not a choice that can be entered from the drop down menu. The standard deviation is really CV% in the table.

Pharmacokinetic Parameters (t1/2 and and MRTinf) by Schedule, Dosing Day, and Dose Cohort for Patients Treated With Vosaroxin as a Single Agent (SPO 0014) for Day 1

Numbers reported are N, mean and CV%. Please note CV% is not a choice that can be entered from the drop down menu. The standard deviation is really CV% in the table.

Pharmacokinetic Parameters (CL) by Schedule, Dosing Day, and Dose Cohort for Patients Treated With Vosaroxin as a Single Agent (SPO 0014) for Day 1

Numbers reported are N, mean and CV%. Please note CV% is not a choice that can be entered from the drop down menu. The standard deviation is really CV% in the table.

Pharmacokinetic Parameters (Vss ) by Schedule, Dosing Day, and Dose Cohort for Patients Treated With Vosaroxin as a Single Agent (SPO 0014) for Day 1

Numbers reported are N, mean and CV%. Please note CV% is not a choice that can be entered from the drop down menu. The standard deviation is really CV% in the table.

Pharmacokinetic Parameters (AUC0-72 and AUCinf ) by Schedule, Dosing Day, and Dose Cohort for Patients Treated With Vosaroxin as a Single Agent (SPO 0014) for Day 4

Numbers reported are N, mean and CV%. Please note CV% is not a choice that can be entered from the drop down menu. Standard Deviation is really CV% in the table.

Pharmacokinetic Parameters (t1/2 and and MRTinf) by Schedule, Dosing Day, and Dose Cohort for Patients Treated With Vosaroxin as a Single Agent (SPO 0014) for Day 4

Numbers reported are N, mean and CV%. Please note CV% is not a choice that can be entered from the drop down menu. The Standard Deviation is really CV% in the table.

Pharmacokinetic Parameters (CL) by Schedule, Dosing Day, and Dose Cohort for Patients Treated With Vosaroxin as a Single Agent (SPO 0014) for Day 4

Numbers reported are N, mean and CV%. Please note CV% is not a choice that can be entered from the drop down menu. The standard deviation is really CV% in the table.

Pharmacokinetic Parameters (Vss ) by Schedule, Dosing Day, and Dose Cohort for Patients Treated With Vosaroxin as a Single Agent (SPO 0014) for Day 4

Numbers reported are N, mean and CV%. Please note CV% is not a choice that can be entered from the drop down menu. The standard deviation is really CV% in the table.

Sunesis Pharmaceuticals

The original Schedule A used a single arm Green Dahlberg design (Green 1992) with 30 patients planned to be treated in Stage I.

Schedule A: 72 mg/m2 Vosaroxin Days 1, 8 and 15

Schedule B was to use a single arm Green Dahlberg 2 stage design with 30 patients planned to be treated in Stage I and 25 patients in Stage II.

Schedule B: 72 mg/m2 Vosaroxin on Days 1 and 8

Schedule C (also implemented under Amendment 2) was a dosing schedule of 72 mg/m2 on Days 1 and 4, and a total of 29 patients were enrolled and treated at this dose

Schedule C: 72 mg/m2 on Days 1 and 4

Amendment 3 added a second dose cohort to Schedule C to treat approximately 10 patients with 90 mg/m2 vosaroxin on Days 1 and 4.

Schedule C: 90 mg/m2 on Days 1 and 4

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Due to the limited sample size in this study, further study is needed to confirm these results. No statistical testings were performed to compare any of the treatment groups. No p-values or odds ratios were reported.

Linda Neuman, Vice President, Clinical Development

The all treated analysis set Included all enrolled patients who received any amount of vosaroxin.

Remission Rate Defined as the Percentage of Patients Whose Respnse is CR or CRp Based on International Working Group (IWG) Response Criteria and Treatment Outcomes Definitions

Leukemia-free Survival (LFS)

Overall Survival

Patients Treated with Vosaroxin as a Single Agent (SPO-0014) on Day 1. Of 113 patients treated, PK data were available for 33 patients who received at least 1 dose of vosaroxin, PK profiles were evaluated for 10 patients in Schedule A, for 9 patients in Schedule B, for 6 patients in Schedule C, and for 8 patients in Schedule C.

Pharmacokinetics Day 1 - Cmax (ng/mL)

Patients Treated with Vosaroxin as a Single Agent (SPO-0014) Day 4. Of 113 patients treated, PK data were available for 33 patients who received at least 1 dose of vosaroxin, PK profiles were evaluated for patients with data on Day 4 for 5 patients in Schedule C, and for 8 patients in Schedule C .

Pharmacokinetics Day 4 Cmax (ng/mL)

30-Day

60-Day

Schedule C (implemented under Amendment 2) was a dosing schedule of 72 mg/m2 on Days 1 and 4, and a total of 29 patients were enrolled and treated at this dose

All Cause Mortality

AUC0-72 (hr.ng/mL)

AUCinf (hr.ng/mL)

Pharmacokinetics Day 1 - AUC0-72 and AUCinf (hr*ng/mL)

t1/2 (hr)

MRTinf (hr)

Patients Treated with Vosaroxin as a Single Agent (SPO-0014) on Day 1. Of 113 patients treated, PK data were available for 33 patients who received at least 1 dose of vosaroxin, PK profiles were evaluated for 10 patients in Schedule A, for 8 patients in Schedule B, for 6 patients in Schedule C, and for 8 patients in Schedule C.

Pharmacokinetics Day 1 - t1/2 (hr) and MRTinf (hr)

Pharmacokinetics Day 1 - CL (L/hr)

Pharmacokinetics Day 1 - Vss (L)

Patients Treated with Vosaroxin as a Single Agent (SPO-0014) on Day 4. Of 113 patients treated, PK data were available for 33 patients who received at least 1 dose of vosaroxin, PK profiles were evaluated for patients with data on Day 4, for 5 patients in Schedule C, and for 8 patients in Schedule C.

Pharmacokinetics Day 4 - AUC0-72 and AUCinf (hr*ng/mL)

Patients Treated with Vosaroxin as a Single Agent (SPO-0014) on Day 4. Of 113 patients treated, PK data were available for 33 patients who received at least 1 dose of vosaroxin, PK profiles were evaluated for patients with data, for 5 patients in Schedule C, and for 7 patients in Schedule C.

Pharmacokinetics Day 4 - t1/2 (hr) and MRTinf (hr)

Patients Treated with Vosaroxin as a Single Agent (SPO-0014) on Day 4. Of 113 patients treated, PK data were available for 33 patients who received at least 1 dose of vosaroxin, PK profiles were evaluated for patients with data on Day 4, for 5 patients in Schedule C, and for 7 patients in Schedule C.

Pharmacokinetics Day 4 - CL (L/hr)

Patients Treated with Vosaroxin as a Single Agent (SPO-0014) on Day 4. Of 113 patients treated, PK data were available for 33 patients who received at least 1 dose of vosaroxin, PK profiles were evaluated for patients with data for Day 4, for 5 patients in Schedule C, and for 7 patients in Schedule C.

Spots Global Cancer Trial Database for nonlymphocytic leukemia