E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute Myeloid Leukaemia and High Risk Myelodysplastic Syndrome |
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E.1.1.1 | Medical condition in easily understood language |
Acute Myeloid Leukaemia and High Risk Myelodysplastic Syndrome |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
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 compare:
To compare a total of three versus four courses of treatment in total, comparing one versus two courses of HD Ara-C in consolidation
In highrisk patients, to evaluate the value of allogeniec stem cell transplantation (SCT), whether standard allogeneic (allo-SCT) or non-myeloblative "mini" allogeneic (mini-SCT)
To assess the clinical value of minimal residual disease monitoring (MRD) for patient overall survival |
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E.2.2 | Secondary objectives of the trial |
The relevance of the molecular and immunophenotypic detection of minimal residual disease
The relevance of the presence of a cytogenetic abnormality in the bone marrow of patients in morphological remission.
Store excess diagnostic material for future research
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
They have one of the forms of acute myeloid leukaemia as defined by the WHO Classification (Appendix A) — this can be any type of de novo or secondary AML or high risk Myelodysplastic Syndrome (defined as >10% bone marrow blasts).
They are considered suitable for intensive chemotherapy.
They should normally be under the age of 60, but patients over this age are eligible if intensive therapy is considered a suitable option.
Patients must have liver function tests within twice the upper limit of the normal local range to receive Mylotarg in course 2 for the Core Binding Factor Leukaemia subset.
Women of child-bearing potential (ie women who are pre-menopausal or not surgically sterile) must use acceptable contraceptive method (abstinence, intrauterine device (IUD) and must have a negative pregnancy test within 2 weeks of trial entry. Pregnant or nursing patients are excluded. Male Patients with partners of childbearing potential must agree to use effective contraception during the study period and a period of 3 months after the last dose of study drug..
They have given written informed consent
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E.4 | Principal exclusion criteria |
They have previously received cytotoxic chemotherapy for AML. [Hydroxycarbamide, or similar low-dose therapy, to control the white count prior to initiation of intensive therapy is not an exclusion.]
They are in blast transformation of chronic myeloid leukaemia (CML).
Have a LV ejection fraction of <45% (such patients can be placed on the D(60)A arm.
They have a concurrent active malignancy.
They are pregnant or lactating
The physician and patient consider that intensive therapy is not an appropriate treatment option. (Such patients should be considered for current NCRI trial for older less fit patients). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Complete remission (CR) achievement and reasons for failure (for induction questions).
Duration of remission, relapse rates and deaths in first CR.
Overall survival.
Toxicity, both haematological and non-haematological
Quality of life for patients in the disease monitoring randomisation
Supportive care requirements (and other aspects of health economics
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
CR is evaluated on an ongoing basis - after each course of induction treatment
Remission duration and survival are evaluated annually
Toxicity is evaluated on ongoing basis
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E.5.2 | Secondary end point(s) |
The relevance of the molecular and immunophenotypic detection of minimal residual disease.
The relevance of the presence of a cytogenetic abnormality in the bone marrow of patients in morphological remission.
To store excess diagnostic material for future research. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
MRD relevance evaluated upon completion of randomisation - may be carried over into next national trial
Material storage is fundamental ongoing plank of the trials portfolio |
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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 | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
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) | 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.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 130 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 160 |
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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Patients will receive approximately 6 months of treatment. Some groups of patients will be eligible for ongoing disease monitoring. The disease status of all patients will be followed for life.
LPLV would be either too crude or too far away to justifiably use as end of trial date. End of trial notification will be submitted when results from the randomisations within the trial are published. |
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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 | 6 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 6 |