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

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

NCT00715637•Antisoma Research

View on ClinicalTrials.gov

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.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

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;
+1 more criteria

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;
+4 more criteria

Locations (158)

UCLA Medical Center

Los Angelas, California, United States

Univ of Southern California Comprehensive Cancer Center

Los Angeles, California, United States

University of California San Francisco

San Francisco, California, United States

University of Colorado Health Sciences Center

Aurora, Colorado, United States

Rocky Mountain Blood and Marrow Transplant Program

Denver, Colorado, United States

Winship Cancer Institute, Emory University

Atlanta, Georgia, United States

The Blood and Marrow Transplant Group of GA

Atlanta, Georgia, United States

Northwestern University School of Medicine

Chicago, Illinois, United States

Rush University Medical Center

Chicago, Illinois, United States

University of Iowa Hospitals

Iowa City, Iowa, United States

Key Dates

Start Date

June 1, 2007

Primary Completion Date

June 1, 2010

Last Updated

October 13, 2010

Enrollment

420

ESTIMATED participants

Conditions

Secondary Acute Myeloid Leukemia (Secondary AML, sAML)

Interventions

Daunorubicin and Cytarabine

DRUG

Amonafide and Cytarabine

DRUG