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Phase III Randomized Study of Amonafide (AS1413) and Cytarabine Versus Daunorubicin and Cytarabine in Patients With Secondary Acute Myeloid Leukemia (AML)- the ACCEDE Study

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ClinicalTrials.gov Identifier: NCT00715637
Recruitment Status : Unknown
Verified October 2010 by Antisoma Research.
Recruitment status was:  Active, not recruiting
First Posted : July 15, 2008
Last Update Posted : October 13, 2010
Sponsor:
Information provided by:
Antisoma Research

Brief Summary:

Amonafide is a DNA intercalating agent and inhibitor of topoisomerase II that has been extensively studied in patients with malignant solid tumors. Amonafide has also been studied in patients with AML.

The purpose of this study is to assess the relative efficacy and safety of amonafide in combination with cytarabine compared to daunorubicin with cytarabine in subjects with documented secondary AML.


Condition or disease Intervention/treatment Phase
Secondary Acute Myeloid Leukemia (Secondary AML, sAML) Drug: Daunorubicin and Cytarabine Drug: Amonafide and Cytarabine Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 420 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase III Open-Label Randomized Study of Amonafide L-Malate in Combination With Cytarabine Compared to Daunorubicin in Combination With Cytarabine in Patients With Secondary Acute Myeloid Leukemia (AML)- The ACCEDE Study
Study Start Date : June 2007
Estimated Primary Completion Date : June 2010


Arm Intervention/treatment
Experimental: Arm A
Amonafide in Combination with Cytarabine
Drug: Amonafide and Cytarabine
Amonafide: 600 mg/m2 IV over 4 hours daily on Days 1-5 (up to max. 2 courses) Cytarabine: 200 mg/m2 IV continuous infusion daily on Days 1-7 (up to max. 2 courses)

Active Comparator: Arm B
Daunorubicin in Combination with Cytarabine
Drug: Daunorubicin and Cytarabine
Daunorubicin: 45 mg/m2 over 30 minutes daily on days 1-3 (up to max. of 2 courses) Cytarabine: 200 mg/m2 IV continuous infusion daily on days 1-7 (up to max. of 2 courses)




Primary Outcome Measures :
  1. Rate of CR + CRi (which includes CRc and CRd) will be determined by assessing the proportion of patients who achieved CR or CRi among all evaluable patients. [ Time Frame: Course 1/Course 2 Day 37 bone marrow assessments and confirmation bone marrow 30 days later ]

Secondary Outcome Measures :
  1. Median duration of remission and median duration of disease free survival. [ Time Frame: Follow-up visits following post-remission therapy ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of AML according to WHO diagnostic criteria (at least 20% blasts in the peripheral blood or bone marrow), with FAB classification other than M3 (Acute Promyelocytic Leukemia), documented by bone marrow aspiration and biopsy performed within 14 days prior to administration of 1st dose of remission induction chemotherapy;
  • Either: Known and documented exposure to specific leukemogenic therapy of a specified nature for a non-myeloid condition; OR Documented diagnosis of MDS according to WHO criteria for at least 3 months prior to study entry, with prior bone marrow aspirate, biopsy and peripheral blood smear documenting MDS available to be submitted for subsequent central pathology review.
  • Age 18 years or older;
  • Eastern Cooperative Oncology Group (ECOG) performance score =< 2;
  • Fertile sexually active patients (men and women) must use an effective method of contraception which must be continued throughout the study.
  • Women of childbearing potential must have a negative serum pregnancy test.
  • Left Ventricular Ejection Fraction (LVEF) >= 50%, as determined by multiple-gated acquisition scan (MUGA) or echocardiogram (ECHO) within 14 days prior to administration of 1st dose of remission induction chemotherapy;
  • Adequate renal function as evidenced by the following laboratory test, obtained within 10 days prior to administration of 1st dose of remission induction chemotherapy: Serum creatinine =< 1.5 x ULN;
  • Adequate hepatic function as evidenced by the following laboratory tests, obtained within 10 days prior to administration of 1st dose of remission induction chemotherapy (unless attributed to hepatic involvement with AML): Total serum bilirubin =< 1.5 x ULN;Serum AST and ALT =< 1.5 x ULN;
  • Ability of the patient to participate fully in all aspects of this clinical trial;
  • Written Informed Consent and HIPAA authorization (USA sites only) must be obtained and documented.

Exclusion Criteria:

  • Histologic diagnosis of FAB M3 Acute Promyelocytic Leukemia;
  • Clinically active CNS leukemia;
  • Prior induction therapy for AML;
  • Known HIV positive;
  • Known active hepatitis B or C, or any other active liver disease;
  • Patients with parenchymal abnormality on screening chest x-ray must have no evidence of pulmonary infection on chest tomography (CT) prior to starting remission induction therapy.
  • Any major surgery or radiation therapy within 4 weeks prior to study entry;
  • Prior cytotoxic chemotherapy for MDS within 4 weeks prior to study entry (patients with rapidly rising blast count may be enrolled within 4 weeks of prior cytotoxic chemotherapy with waiver from the Medical Monitor);
  • Persistent chronic non-hematologic toxicity (other than alopecia) greater than grade 1 from prior therapy for MDS;
  • Serious concomitant illnesses (for example, pulmonary infiltrate, unstable angina or myocardial infarction or stroke within 3 months prior to study entry, congestive heart failure AHA class 2 or greater, uncontrolled hypertension, uncontrolled diabetes, actively bleeding gastric ulcer, etc.), which in the investigator's opinion would not make the patient a good candidate for the trial;
  • Pregnant or breast feeding;
  • History of clinically significant allergic reactions attributed to compounds of similar chemical or biological composition to amonafide, cytarabine or daunorubicin;
  • Prior enrollment in this trial;
  • Any other known condition (e.g., familial, sociological, or geographical) or behavior (including substance dependence or abuse, psychological or psychiatric illness), which in the investigator's opinion would make the patient a poor candidate for the trial.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00715637


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Sponsors and Collaborators
Antisoma Research

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Bina Tejura/Medical Director, Antisoma
ClinicalTrials.gov Identifier: NCT00715637     History of Changes
Obsolete Identifiers: NCT00509912
Other Study ID Numbers: 509912
First Posted: July 15, 2008    Key Record Dates
Last Update Posted: October 13, 2010
Last Verified: October 2010

Keywords provided by Antisoma Research:
AML
Leukemia
MDS
Amonafide
Cytarabine
Daunorubicin
Lymphatic disorders

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasm Metastasis
Neoplasms by Histologic Type
Neoplasms
Neoplastic Processes
Pathologic Processes
Cytarabine
Amonafide
Daunorubicin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors