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Phase 3 Randomized Study of Amonafide (AS1413) and Cytarabine Versus Daunorubicin and Cytarabine in Patients With Secondary Acute Myeloid Leukemia (AML)
This study is currently recruiting participants.
Verified by Antisoma Research, October 2008
Sponsored by: 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 (sAML)
Drug: Daunorubicin and Cytarabine
Drug: Amonafide and Cytarabine
Phase III

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic
Drug Information available for: Cytarabine Cytarabine hydrochloride Daunorubicin hydrochloride Daunorubicin Amonafide Malic acid
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Open Label, Parallel Assignment, Safety/Efficacy Study
Official Title: Phase 3 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)

Further study details as provided by Antisoma Research:

Primary Outcome Measures:
  • Rate of confirmed CR + CRi (which includes CRc and CRd) will be determined by assessing the proportion of patients who achieved confirmed 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: 350
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

Locations
United States, California
University of California San Francisco Recruiting
San Francisco, California, United States
Contact: Natalie Jeha     415-476-4126     njeha@medicine.ucsf.edu    
Contact: Beth Davis     415-502-3176     bdavis@medicine.ucsf.edu    
Principal Investigator: Lloyd Damon            
UCLA Medical Center Recruiting
LA, California, United States, 90095
Contact: Rose Malone     310-794-0244     rmalone@mednet.ucla.edu    
Principal Investigator: Schiller Gary, MD            
United States, Colorado
Rocky Mountain Blood and Marrow Transplant Program Recruiting
Denver, Colorado, United States
Contact: Juli Murphy     303-285-5087     Juli.Murphy@usoncology.com    
Contact: Nicole Stephens     303-336-2183     Nicole.Stephens@usoncology.com    
Principal Investigator: Michael Maris, MD            
United States, Florida
M. D. Anderson Cancer Center Orlando Recruiting
Orlando, Florida, United States
Contact: Terra Warner     321-841-1907     Terra.warner@orhs.org    
Principal Investigator: Jose E Sarriera, MD            
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States
Contact: Richard M Stone, MD            
Contact: Galinski Ilene, APRN-C            
Principal Investigator: Richard M Stone, MD            
United States, Michigan
University of Michigan Cancer Center Recruiting
Ann Arbor, Michigan, United States
Contact: Amanda Dressel     734-763-0005     adressel@umich.edu    
Contact: Irene Ryan     734-647-9757     iryan@umich.edu    
Principal Investigator: Harry Erba, MD            
United States, New York
Northshore Hospital - Monter Cancer Center Recruiting
Lake Success, New York, United States
Contact: Vivian O'Mara     516-734-8940     VOMara@nshs.edu    
Principal Investigator: Steve Allen, MD            
United States, North Carolina
Wake Forest University Health Sciences Recruiting
Winston-Salem, North Carolina, United States
Contact: Jennifer MacLean, BS, RN, OCN     336-713-3539     jemaclea@wfubmc.edu    
Contact: Scarlett Hutchens, RN, BSN     336-713-6915     snhutche@wfubmc.edu    
Principal Investigator: Bayard Powell, MD            
Sponsors and Collaborators
Antisoma Research
  More Information

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

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

Study placed in the following topic categories:
Daunorubicin
Lymphatic Diseases
Leukemia
Acute myelogenous leukemia
Neoplasm Metastasis
Leukemia, Myeloid
Amonafide
Leukemia, Myeloid, Acute
Acute myelocytic leukemia
Cytarabine

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

ClinicalTrials.gov processed this record on January 16, 2009