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Study Summary
No. 2010-0692:.......Leukemia......Farhad Ravandi-Kashani......Leukemia
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Study Summary Title
Study Summary
Number:
2010-0692
Study Title:A Phase 3, Randomized, Controlled, Double-Blind , Multinational Clinical Study of the Efficacy and Safety of Vosaroxin and Cytarabine Versus Placebo and Cytarabine in Patients With First Relapsed or Refractory Acute Myeloid Leukemia (VALOR)
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Physician New Patient Referral
Name:Farhad Ravandi-KashaniPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:LeukemiaReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-792-7305
Contact us about clinical trials
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General Information
Disease Group:LeukemiaSupported By:Sunesis Pharmaceuticals, Inc.
Phase of Study:Phase IIIReturn
Visit:
Treatment
Agents:
Cytarabine
Vosaroxin
Home Care:
Treatment Loc:Both at MDACC & and Other Sites
Estimated
Length of Stay
in Houston:
Description/
Intervention:
The goal of this clinical research study is to compare the safety and
effectiveness of combining cytarabine with the study drug vosaroxin, versus
cytarabine and a placebo, in treating patients with relapsed or refractory
AML. Researchers want to compare how long these 2 study drug combinations may
be able to help control the disease.
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Study Objectives / Outcomes
Primary Objective

The primary objective is to compare overall survival (OS) between treatment groups of patients treated with vosaroxin and cytarabine versus patients treated with placebo and cytarabine.

Secondary Objectives
  • Compare complete remission (CR) rate based on International Working Group (IWG) response criteria, between treatment groups
  • Compare safety and tolerability between treatment groups

Tertiary Objectives

Compare the following parameters between treatment groups:
  • Combined CR rate, defined as CR+CRp+CRi based on IWG response criteria. CRp is a CR with incomplete platelet recovery and CRi is a CR with incomplete recovery of platelets or neutrophils
  • Overall remission (OR) rate, defined as CR+CRp+CRi+PR based on IWG response criteria. PR is partial remission
  • 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
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Study Status Information
Study Activation / Registration Date:
IRB Review and Approval Date:12/03/2010
Study Type:Phase Iii
Recruitment Status:Open
Projected Accrual:675
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Enrollment Eligibility
If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:1) Able to understand and provide written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization, as appropriate

2) At least 18 years of age

3) Diagnosis of acute myeloid leukemia (AML) by World Health Organization (WHO) classification

4) First relapsed or refractory AML with at least 5% blasts by bone marrow biopsy or aspirate, or at least 1% blasts in peripheral blood, and meeting the following criteria:MUST MEET (a), (b), and (c). (a) First relapse occurred at least 90 days to 24 months after the first CR or CRp; (b) The first CR or CRp had to result from no more than 2 cycles of cytotoxic chemotherapy. At least 1 induction cycle must have consisted of an anthracycline (or anthracenedione) and cytarabine combination with a reasonable schedule/dose of anthracycline in the judgment of the investigator; (c) The re-emergence of at least 5% leukemic blasts in bone marrow is not attributable to other causes, regardless of new or recurrent dysplastic changes or extramedullary disease, or the re-emergence of at least 1% blasts in the peripheral blood is not attributable to other causes such as regenerating marrow.

5) Continued from #4: The date of relapse is the date of the first bone marrow examination that demonstrated the re-emergence of at least 5% leukemic blasts, or is the date of the first peripheral blood test that demonstrated at least 1% blasts not attributable to other causes such as regenerating marrow. Allowed:  Unlimited cycles/regimens of consolidation for first CR or CRp  Transplantation for AML (allogeneic or autologous) allowed unless within 90 days of randomization  Maintenance therapy with hypomethylating or biologic agents until relapse.

6) Continued from #5: REFRACTORY MUST MEET EITHER (e) and (g) OR (f) and (g): (e) Persistent AML was documented by bone marrow biopsy or aspirate at least 28 days after day 1 of the first induction cycle of 1 or 2 cycles of cytotoxic chemotherapy; (f) Re-emergence of at least 5% leukemic blasts in bone marrow or at least 1% blasts in peripheral blood is not attributable to other causes such as regenerating marrow, and was less than 90 days after the first CR or CRp; (g) Prior induction therapy had to include no more than 2 cycles of cytotoxic chemotherapy. At least 1 induction cycle must have consisted of an anthracycline (or anthracenedione) and cytarabine combination with a reasonable schedule/dose of anthracycline in the judgment of the investigator.

7) Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

8) Local clinical laboratory values as follows: Serum creatinine </= 2.0 mg/dL; Total bilirubin </= 1.5 x the upper limit of normal (ULN), unless due to Gilbert's syndrome; Aspartate aminotransferase (AST) </= 2.5 x ULN; Alanine aminotransferase (ALT) </= 2.5 x ULN.

9) Left ventricular ejection fraction (LVEF) at least 40% by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO)

10) Clinically significant nonhematologic toxicity after prior chemotherapy has recovered to grade 1 per Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 or newer

11) Females must be surgically or biologically sterile or postmenopausal (amenorrheic for at least 12 months) or if of childbearing potential, must have a negative urine or serum pregnancy test within 14 days before randomization, and must agree to use an adequate method of contraception during the study until 30 days after the last treatment. Males must be surgically or biologically sterile or agree to use an adequate method of contraception during the study until 30 days after the last treatment

Exclusion Criteria:1) Acute promyelocytic leukemia (APL)

2) More than 2 cycles of induction therapy for AML

3) Completion of a single cycle of treatment containing a total dose of 5 g/m2 or more of cytarabine within the 90 days before randomization

4) Allogeneic or autologous transplant for AML with infusion of stem cells within 90 days before randomization, or on active immunosuppressive therapy for graft-versus-host disease (GVHD) or GVHD prophylaxis within 2 weeks before randomization

5) Known or suspected central nervous system (CNS) involvement of active AML

6) Other active malignancies (including other hematologic malignancies) or other malignancies within 12 months before randomization, except nonmelanoma skin cancer or cervical intraepithelial neoplasia

7) Uncontrolled active infection of any type: Infections under control with antibiotic treatment are acceptable; Chronic hepatitis is acceptable

8) Uncontrolled invasive fungal infection (positive blood or tissue culture)

9) History of myocardial infarction (MI), unstable angina, cerebrovascular accident, or transient ischemic attack (CVA/TIA) within 3 months before randomization

10) Prior or current therapy: Hydroxyurea or medications to reduce blast count within 24 hours before randomization; Treatment with an investigational product within 14 days before randomization, or not recovered from all acute effects of previously administered investigational products

11) Hemodialysis or peritoneal dialysis required

12) Prior exposure to vosaroxin

13) Pregnant or breastfeeding

14) Known HIV seropositivity

15) Any other medical, psychological, or social condition that may interfere with study participation or compliance, or compromise patient safety in the opinion of the investigator or medical monitor

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Links
Registration Number: NCT01191801
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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