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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00715637




Registration number
NCT00715637
Ethics application status
Date submitted
14/07/2008
Date registered
15/07/2008
Date last updated
13/10/2010

Titles & IDs
Public title
Phase III Randomized Study of Amonafide (AS1413) and Cytarabine Versus Daunorubicin and Cytarabine in Patients With Secondary Acute Myeloid Leukemia (AML)- the ACCEDE Study
Scientific 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
Secondary ID [1] 0 0
509912
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Secondary Acute Myeloid Leukemia (Secondary AML, sAML) 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Daunorubicin and Cytarabine
Treatment: Drugs - Amonafide and Cytarabine

Experimental: Arm A - Amonafide in Combination with Cytarabine

Active comparator: Arm B - Daunorubicin in Combination with Cytarabine


Treatment: Drugs: 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)

Treatment: Drugs: 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)
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
Course 1/Course 2 Day 37 bone marrow assessments and confirmation bone marrow 30 days later
Secondary outcome [1] 0 0
Median duration of remission and median duration of disease free survival.
Timepoint [1] 0 0
Follow-up visits following post-remission therapy

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
UNKNOWN
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/06/2007
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
420
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,SA,VIC,WA
Recruitment hospital [1] 0 0
The Canberra Hospital - Garran
Recruitment hospital [2] 0 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [3] 0 0
Westmead Hospital - Westmead
Recruitment hospital [4] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [5] 0 0
Box Hill Hospital - Box Hill
Recruitment hospital [6] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [7] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [8] 0 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 0 0
2605 - Garran
Recruitment postcode(s) [2] 0 0
2065 - St Leonards
Recruitment postcode(s) [3] 0 0
2145 - Westmead
Recruitment postcode(s) [4] 0 0
5000 - Adelaide
Recruitment postcode(s) [5] 0 0
- Box Hill
Recruitment postcode(s) [6] 0 0
3002 - Melbourne
Recruitment postcode(s) [7] 0 0
3004 - Melbourne
Recruitment postcode(s) [8] 0 0
6000 - Perth
Recruitment outside Australia
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California
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Tennessee
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Utah
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Argentina
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Buenos Aires
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Argentina
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Ciudad Autónoma de Bs. As.
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Argentina
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Cordoba
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Rosario - Santa Fe
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Graz
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Pisa
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Roma
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Rome
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Barcelona
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Valencia
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Taipei
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Ukraine
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Cherkasy
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Dnipropetrovsk
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Ivano-Frankivsk
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Khmelnytsky
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Lviv
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Poltava
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Vinnytsya
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Ukraine
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Zhytomyr
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United Kingdom
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Wales
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United Kingdom
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London
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United Kingdom
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Oxford

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Antisoma Research
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT00715637
Trial related presentations / publications
Stone RM, Mazzola E, Neuberg D, Allen SL, Pigneux A, Stuart RK, Wetzler M, Rizzieri D, Erba HP, Damon L, Jang JH, Tallman MS, Warzocha K, Masszi T, Sekeres MA, Egyed M, Horst HA, Selleslag D, Solomon SR, Venugopal P, Lundberg AS, Powell B. Phase III open-label randomized study of cytarabine in combination with amonafide L-malate or daunorubicin as induction therapy for patients with secondary acute myeloid leukemia. J Clin Oncol. 2015 Apr 10;33(11):1252-7. doi: 10.1200/JCO.2014.57.0952. Epub 2015 Mar 2.
Lindsley RC, Mar BG, Mazzola E, Grauman PV, Shareef S, Allen SL, Pigneux A, Wetzler M, Stuart RK, Erba HP, Damon LE, Powell BL, Lindeman N, Steensma DP, Wadleigh M, DeAngelo DJ, Neuberg D, Stone RM, Ebert BL. Acute myeloid leukemia ontogeny is defined by distinct somatic mutations. Blood. 2015 Feb 26;125(9):1367-76. doi: 10.1182/blood-2014-11-610543. Epub 2014 Dec 30.
Public notes

Contacts
Principal investigator
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Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
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Contact person for public queries
Name 0 0
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Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00715637