E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute myeloid leukemia after failure of a single standard dose cytarabine based frontline induction regimen. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10001941 |
E.1.2 | Term | AML |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
- To determine if AEG35156 can enhance the combined complete remission (CR) and CR with incomplete platelet recovery (CRp) rate of high-dose cytarabine and idarubicin in AML following failure of a single standard dose cytarabine based frontline induction regimen.
- To determine if AEG35156 can enhance response duration following high-dose cytarabine and idarubicin in AML following failure of a single standard dose cytarabine based frontline induction regimen. |
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E.2.2 | Secondary objectives of the trial |
- To determine if AEG35156 can enhance overall survival following high-dose cytarabine and idarubicin in AML following failure of a single standard dose cytarabine based frontline induction regimen.
- To determine the safety of adding AEG35156 to high-dose cytarabine and idarubicin in AML following failure of a single standard dose cytarabine based frontline induction regimen.
- To study the pharmacokinetics of AEG35156 when used in combination with cytarabine and idarubicin |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Patients with AML, except those with APL (acute promyelocytic leukemia), failing a single standard dose cytarabine based frontline induction regimen. The diagnosis of refractory AML is based on the presence of either > 10% blasts in marrow or blood or 5-10% blasts in either site together with cytopenia (Hb < 10 g/dL, or platelets < 100 x 10^9/L, or neutrophil count < 1.0 x 10^9/L). - Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤2. - Patients must be ≥18 years old. - Male, or female patients who are post-menopausal (amenorrhagic for at least 12 months), or surgically or biologically sterile. Females of childbearing potential must have a negative serum pregnancy test within 72 hours prior to the 1st infusion in the study and using adequate forms of contraception for the duration of the study, including 30 days after the last treatment. Males should avoid fathering children during the course of the study. Patients and their partners with reproductive potential must use an effective contraceptive method while the patient is on the study treatment and for 30 days after the last treatment. Adequate methods of contraception are double barrier methods (condoms with spermicidal jelly or foam, and diaphragm with spermicidal jelly or foam), oral, depot and injectable contraceptives, IUD, and surgical sterilization. Single barrier methods, rhythm methods, abstinence or sterility of a partner will not be considered adequate contraception. - Patients must have adequate organ and immune function as indicated by the following laboratory values: Parameter Laboratory Values Serum creatinine; ≤2.0 mg/dL (≤177 μmol/L) Total Bilirubin ≤2.0 mg/dL (≤34 μmol/L) AST (SGOT) and ALT (SGPT) ≤3 X ULN * *ULN: Institution’s upper limit of normal. - The patient must understand, be able and willing and likely to fully comply with study procedures, including scheduled follow-up, and restrictions. |
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E.4 | Principal exclusion criteria |
- Clinical evidence of ongoing grade 3 or 4 non-hematological toxicities from the initial standard dose cytarabine-based induction chemotherapy. - Patients with a prior history of peripheral neuropathy of grade 2 or higher. - Clinical evidence of active CNS leukemic involvement. - Active and uncontrolled infection. Patients with an infection who are under active treatment with antibiotics and whose infections are controlled may be entered to the study. - Current evidence of invasive fungal infection (blood or tissue culture). - Current evidence of an active second malignancy except for non-melanoma skin cancer. - Uncontrolled medical problems, unrelated to the malignancy, or of sufficient severity that in the opinion of the investigator, impair a patient’s ability to give informed consent or unacceptably reduce the safety of the proposed treatment. - Neurological or psychiatric disorders that would interfere with consent or study follow-up. - Known or suspected intolerance or hypersensitivity to the study drugs [or closely related compounds] or any of their stated ingredients. Study drugs being the antisense, cytarabine and idarubicin. - History of alcohol or other substance abuse within the last year. - Use of another investigational agent within the last 14 days prior to enrolment. Patients who have received a previous antisense agent in the last 90 days will be excluded. - Female patients who are pregnant, lactating, or with a positive pregnancy test at screening must be excluded. - Patients who have previously been enrolled into this study and subsequently withdrawn must also be excluded.
Both men and women and members of all races and ethnic groups are eligible for this trial. |
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E.5 End points |
E.5.1 | Primary end point(s) |
- To determine if AEG35156 can enhance the combined complete remission (CR) and CR with incomplete platelet recovery (CRp) rate of high-dose cytarabine and idarubicin in AML following failure of a single standard dose cytarabine based frontline induction regimen. - To determine if AEG35156 can enhance response duration following high-dose cytarabine and idarubicin in AML following failure of a single standard dose cytarabine based frontline induction regimen.
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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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | Yes |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
comparison between chemotherapy + study drug AEG35156 versus chemotherapy alone |
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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 | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
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 | No |
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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End of trial is defined as LPLV (Last Patient Last Visit) |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
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 |