E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
secondary acute myeloid leukemia |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10000886 |
E.1.2 | Term | Acute myeloid leukemia |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The rate of complete remission with or without hematopoietic recovery (CR + CRi) |
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E.2.2 | Secondary objectives of the trial |
- The rate of CR + CRi that is maintained for a duration of at least 30 days. - The rate of confirmed CR + CRi. - Rate of CR + CRi within different clinical subsets; - Rate of response overall and within different clinical subsets; - Rate of response for each individual response category overall and within different clinical subsets; - Median duration of remission; - Median duration of disease free survival (DFS); - Proportion of patients remaining in remission at 6, 12 and at 18 months; - Median duration of overall survival (OS) for all patients, for all patients in remission and for each individual response category; - Correlation of clinical responses, duration of responses, DFS and OS with cytogenetic abnormalities, and expression and function of Pgp; - Correlation of PK exposure of amonafide and N-acetyl amonafide with both safety and efficacy assessments. - The rate of bone marrow or stem cell transplant. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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. 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. |
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E.4 | Principal 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 infection on screening chest x-ray should have chest computed tomography (CT) prior to starting remission induction therapy to confirm absence or presence of pulmonary infection.
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.
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E.5 End points |
E.5.1 | Primary end point(s) |
The rate of CR + CRi will be determined by assessing the proportion of all randomized patients who achieved CR or CRi. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 70 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |