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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
This study is currently recruiting participants.
Verified by Antisoma Research, December 2009
First Received: July 14, 2008   Last Updated: December 16, 2009   History of Changes
Sponsor: Antisoma Research
Information provided by: Antisoma Research
ClinicalTrials.gov Identifier: NCT00715637
  Purpose

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 Intervention Phase
Secondary Acute Myeloid Leukemia (Secondary AML, sAML)
Drug: Daunorubicin and Cytarabine
Drug: Amonafide and Cytarabine
Phase III

Study Type: Interventional
Study Design: Treatment, Randomized, Open Label, Parallel Assignment, Safety/Efficacy Study
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

Resource links provided by NLM:


Further study details as provided by Antisoma Research:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Median duration of remission and median duration of disease free survival. [ Time Frame: Follow-up visits following post-remission therapy ] [ Designated as safety issue: No ]

Estimated Enrollment: 450
Study Start Date: June 2007
Estimated Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Arm A: Experimental
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)
Arm B: Active Comparator
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)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00715637

Contacts
Contact: Bill Lundberg, MD 617-225-0522 ext 164 bill.lundberg@antisoma.com

  Show 138 Study Locations
Sponsors and Collaborators
Antisoma Research
  More Information

No publications provided

Responsible Party: Antisoma ( J. Kris Piper, VP Regulatory Affairs )
Study ID Numbers: 509912
Study First Received: July 14, 2008
Last Updated: December 16, 2009
ClinicalTrials.gov Identifier: NCT00715637     History of Changes
Health Authority: United States: Food and Drug Administration

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

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

ClinicalTrials.gov processed this record on February 08, 2010