| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | Acute myeloid leukaemia
High Risk Myelodysplastic Syndrome | |
| E.1.1.1 | Medical condition in easily understood language | | AML and MDS are malignant conditions of the bone marrow. They both result in failure of the bone marrow to manufacture enough blood cells because the marrow contains too many leukaemia cells | |
| E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 | | E.1.2 | Level | PT | | E.1.2 | Classification code | 10028533 | | E.1.2 | Term | Myelodysplastic syndrome | | E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) | |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 | | E.1.2 | Level | PT | | E.1.2 | Classification code | 10000880 | | E.1.2 | Term | Acute myeloid leukaemia | | E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) | |
| 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 overall survival in patient groups of differing risk status by assessing time from randomisation into particular arms of the study until death from any cause. | |
| E.2.2 | Secondary objectives of the trial | • Complete remission (CR or CRi) achievement after two courses of
induction, and reasons for failure (for induction questions)
• Duration of remission, relapse rates and deaths in first CR
• Toxicity, both haematological and non-haematological
• Supportive care requirements (and other aspects of health
economics)
• To assess quality of life in all patient groups. | |
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria | •They have one of the forms of CD33 positive (any level) favourable,
standard risk or unknown cytogenetics, de novo AML as defined by the
WHO Classification
• WHO performance status 0-2.
• They are considered suitable for intensive chemotherapy.
• Age 16 to 60 years of age, with the following caveats: o Patients over
60 are eligible if intensive therapy is considered a suitable option o
Patients must be ≥18 to be eligible to receive Midostaurin
• A negative pregnancy test within 2 weeks prior to trial entry in WOCBP
to be repeated throughout the trial prior to each course of protocol
treatment.
• Sexually mature males and females must agree to use an adequate and
medically accepted method of contraception throughout the study and
for 6 months following treatment (unless patient is female and received
Mylotarg- in which case it should be 7 months) if they or their sexual
partners are women of childbearing potential (WOCBP).
• Written informed consent. · Patients must have Serum Alanine
Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤2.5
×ULN and bilirubin ≤2×ULN · For Midostaurin: Patients must have a FLT3
TKD or ITD mutation detected by the central laboratory in Cardiff | |
| E.4 | Principal exclusion criteria | •Patients with APL, secondary AML, therapy-related AML, high risk
myelodysplastic syndrome with <20% bone marrow blasts, or de novo
AML with known adverse risk cytogenetics.
• Concurrent active malignancy requiring treatment.
• Patients who are pregnant or lactating.
• Known infection with Human Immunodeficiency Virus (HIV).
• Previous cytotoxic chemotherapy for AML. Note: Hydroxycarbamide, or
similar low-dose therapy, to control the white count prior to initiation of
intensive therapy is not an exclusion
• Blast transformation of chronic myeloid leukaemia (CML).
• The physician and patient consider that intensive therapy is not an
appropriate treatment option. | |
| E.5 End points |
| E.5.1 | Primary end point(s) | |
| E.5.1.1 | Timepoint(s) of evaluation of this end point | Protocol V9.0 requires 250 patients to be recruited over a 1-year period.
A 2-year follow up period will then begin. Patient data from recruitment
to protocol V9.0 will be used in addition with recruitment data from
previous protocol versions to ensure that all protocol questions are
answered. | |
| E.5.2 | Secondary end point(s) | · Complete remission (CR or CRi) achievement after two courses of
induction and reasons for failure (for induction questions)
· Duration of remission, relapse rates and deaths in first CR
· Toxicity, both haematological and non-haematological
· Supportive care requirements (and other aspects of health economics)
· Quality of life for all new patients, and the now closed disease
monitoring randomisation and APL trial arm. | |
| E.5.2.1 | Timepoint(s) of evaluation of this end point | Protocol V9.0 requires 250 patients to be recruited over a 1-year period.
A 2-year follow up period will then begin. Patient data from recruitment
to protocol V9.0 will be used in addition with recruitment data from
previous protocol versions to ensure that all protocol questions are | |
| 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 | 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) | 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 | No |
| 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 | 96 |
| 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 | No |
| 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 | | Denmark | | New Zealand | | United Kingdom | |
| 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 | The treatment phase will be followed by a follow-up period which will
continue until patients withdraw consent or die, or the trials unit
confirms otherwise.
The end of the trial is defined as the date of final data capture to meet
the trial endpoints. In this case end of trial is defined as last patient
last visit, this will be determined when sufficient events have been
reached and all sites will be notified when this is the case. | |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 8 |
| E.8.9.1 | In the Member State concerned months | 7 |
| E.8.9.1 | In the Member State concerned days | 1 |
| E.8.9.2 | In all countries concerned by the trial years | 8 |
| E.8.9.2 | In all countries concerned by the trial months | 7 |
| E.8.9.2 | In all countries concerned by the trial days | 1 |
