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)

• Register: EUCTR
• Last refreshed on: 7 January 2013
• Main ID: EUCTR2007-004427-38-IT
• Date of registration: 27/01/2009
• Prospective Registration: Yes
• Primary sponsor: ANTISOMA
• Public 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)
• Scientific 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)
• Date of first enrolment: 09/02/2009
• Target sample size: 420
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-004427-38
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Austria, Czech Republic, Estonia, France, Germany, Greece, Hungary, Italy, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
a)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. If a bone marrow aspirate and biopsy were obtained within 28 days prior to the first dose of remission induction therapy then these tests may be submitted for central review and a repeat screening bone marrow does not need to be conducted. b.) Either a. Known and documented exposure to specific leukemogenic therapy of a specified nature for a non-myeloid condition. The specific leukemogenic therapies are listed in Appendix 2; OR b. Documented diagnosis of MDS or chronic myelomonocytic leukemia (CMML) according to WHO criteria for at least 3 months prior to study entry; must also have a prior bone marrow aspirate or biopsy documenting MDS (or pathology report if bone marrow samples cannot be obtained) available to be submitted for subsequent central pathology review c.) Age 18 years or older; d.) Eastern Cooperative Oncology Group (ECOG) performance score < 2; e.) Fertile sexually active patients (men and women) must use an effective method of contraception which must be continued throughout the study. f.) Women of childbearing potential must have a negative serum pregnancy test. A woman of childbearing potential is defined as one who is biologically capable of becoming pregnant. This includes women who are using contraceptives or whose sexual partners are either sterile or using contraceptives; g.) 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; if a LVEF by MUGA or ECHO was done within 28 days prior to the first dose of remission induction therapy then a repeat screening LVEF does not need to be conducted; h.) Adequate renal function as evidenced by the following laboratory test, obtained within 14 days prior to administration of 1st dose of remission induction chemotherapy: Serum creatinine < 1.5 x ULN; i.) Adequate hepatic function as evidenced by the following laboratory tests, obtained within 14 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; j.) Ability of the patient to participate fully in all aspects of this clinical trial; k.) Written Informed Consent and HIPAA authorization (USA sites only) must be obtained and documented.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
a.) Histologic diagnosis of FAB M3 Acute Promyelocytic Leukemia; b.) Clinically active CNS leukemia; c.) Prior induction therapy for AML; d.) Known HIV positive; e.) Known active hepatitis B or C, or any other active liver disease; f.) Evidence of pulmonary infection. Patients with evidence of pulmonary on screening chest x-ray must have no evidence of pulmonary infection on chest tomography (CT) prior to starting remission induction therapy. g.) Any major surgery or radiation therapy within 4 weeks prior to study entry; h.) 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); i.) Persistent chronic non-hematologic toxicity (other than alopecia) greater than grade 1 from prior therapy for MDS; j.) 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; k.) Pregnant or breast feeding; l.) History of clinically significant allergic reactions attributed to compounds of similar chemical or biological composition to amonafide, cytarabine or daunorubicin; m.) Prior enrollment and randomization in this trial; n.) 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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Patient with secondary acute myeloid leukemia.
MedDRA version: 14.1 Level: LLT Classification code 10000886 Term: Acute myeloid leukemia System Organ Class: 100000004864

Intervention(s)

Product Name: Amonafide L-malate
Product Code: NA
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Amonafide
CAS Number: 69408-81-7
Concentration unit: mg/l milligram(s)/litre
Concentration number: 100-

Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: Daunorubicin

Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Cytarabine

Primary Outcome(s)

Primary end point(s): The rate of complete remission with or without complete hematopoietic recovery (CR+CRi)

Secondary Objective: - The rate of CR + CRi that is maintained for a duration of at least 30 days. - The rate of confirmed CR + CRi. - The rate of CR + CRi within different clinical subsets(AML following MDS, AML following leukemogenic therapy, etc); - The rate of response [CR + CRi + partial response (PR)] overall and within different clinical subsets; - The rate of response for each individual response category (CR, CRi, CRc, CRd and PR) overall and within different clinical subsets; - The median duration of remission for all patients in remission and for each individual response category (CR, CRi, CRc, CRd); - The median duration of disease free survival (DFS) for all patients in remission and for each individual response category (CR, CRi, CRc, CRd); - The proportion of patients remaining in remission (CR, CRi, CRc, CRd) at 6 months, at 12 months, and at 18 months; - The median duration of overall survival (OS) for all patients, for all patients in remission and for each individual response

Main Objective: The rate of complete remission with or without hematopoietic recovery.

Secondary ID(s)

0001A3-300-GL

2007-004427-38-DE