E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute myeloid leukemia (AML), de novo, FAB classification other than M3 or WHO classification other than APL t(15,17), > 60 years, abesence of any other antededent hematologic disease of >8 months, ECOG performance status 0, 1 or 2, life expectancy > 3 months, adequate organ functions to receive intensive chemotherapy |
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E.1.1.1 | Medical condition in easily understood language |
Acute myeloid leukemia (AML), de novo, FAB classification other than M3 or WHO classification other than APL t(15,17) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10000886 |
E.1.2 | Term | Acute myeloid leukemia |
E.1.2 | System Organ Class | 100000004864 |
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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 |
Tolerability (number of cycles of consolidation therapy; toxicity) of intensified consolidation therapy in elderly AML patients Adverse event profile
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E.2.2 | Secondary objectives of the trial |
The rate of complete remission (CR) following induction chemotherapy Overall survival, continuous complete remission and disease-free survival Evaluation of prognostic factors: Age, (<75 years, ≥75years), karyotype, molecular fusion proteins (multiplex-PCR), mutations (KIT, NPM, FLT3), serum tryptase level at diagnosis and at complete hematologic remission, histologic markers (% CD34 positive cells, microvessel density, fibrosis) Quality of life (ECOG, Charlson Score) Percent patients with ANC≥500/µL on day 10 Incidence and duration of febrile neutropenia (=days per cycle with ANC <500 cells/µL and temperature ≥38°C) Days in hospital Comparison between cycle 3 and cycle 4 with regard to the duration of ANC <500 cells/µL and duration of hospitalisation Efficacy and Pharmacokinetic of PEG-Filgrastim in Consolidation therapy
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Patients must have a morphologically confirmed diagnosis of AML with FAB classification other than M3 or WHO classification other than APL t(15;17), based on bone marrow aspiration and biopsy. • Patients must have reached their 60th birthday. • ECOG performance status of 0, 1, or 2. • Life expectancy >3 months • Adequate organ function to receive intensive chemotherapy • Written informed consent.
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E.4 | Principal exclusion criteria |
• Patients with APL • Subjects with blast transformation of chronic myeloid leukemia or leukemia developing from myeloproliferative diseases. • Leukemia following a documented myelodysplasic syndrome known for more than 8 months. • Patients with a concurrent malignancy, except stage 1 cervical intraepithelial carcinoma and basal cell carcinoma. • Previous treatment with chemotherapy. • Patients who have known HIV-infection. • Impaired hepatic or renal function i.e.: ALT and/or AST > 2.5 x ULN; bilirubin > 2 x ULN; Serum creatinin > 2 x ULN (after adequate hydration) (unless these are most likely caused by AML organ infiltration) • Severe cardiac disease: Patients must not have a severely reduced left ventricular function (shortening fraction <20% as assessed by 2-D ECHO within 6 months prior initiation of induction therapy), unstable cardiac arrhythmias or unstable angina. • Severe obstructive or restrictive pulmonary disease. • Patients must not have received systemic chemotherapy or more than one dose of intrathecal chemotherapy for acute leukemia. Administration of hydroxyurea or etoposid to control high blast cell counts prior to induction-chemotherapy is permitted. • Psychiatric, addictive, or any disorder, which compromises ability to give truly informed consent for this study. • Concerns for subject’s compliance with the protocol procedures.
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E.5 End points |
E.5.1 | Primary end point(s) |
• The number of chemotherapy-cycles patients received (including patients fraction having received all cycles of consolidation chemotherapy) and the drop out rate • Adverse event profile
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
All endpoints will be evaluated at the end of the study. |
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E.5.2 | Secondary end point(s) |
• Proportion of subjects in CR after induction therapy • For all survival, continuous complete remission and disease free survival • Quality of life (ECOG, Charlson Score) • Identification of prognostic factors including age (<75 years, ≥75years), karyotype, initial leukocyte count, molecular fusion proteins (multiplex-PCR), mutations (KIT, NPM, FLT3), serum tryptase level at diagnosis and at complete hematologic remission, histologic markers (% CD34 positive cells, microvessel density, fibrosis), flow cytometric parameters (progenitor subsets, MRD) • Relapse rate after intensified chemotherapy • Percent patients with ANC ≥500/μL on day 10 • Incidence and duration of febrile neutropenia (=days/cycle; ANC <500 cells/μL, temperature ≥38°C) • Days in hospital • Comparison between cycle 3 and 4 with regard to the duration of ANC <500 cells/μL and duration of hospitalisation • Pharmacokinetics of Peg-Filgrastim |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
All endpoints will be evaluated at the end of the study. |
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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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 5 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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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End of the trial is after last cycle of induction or consolidation therapy of the last patient.
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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 | 7 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |