E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Late Stage Acute Myeloid Leukaemia |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066764 |
E.1.2 | Term | Acute myeloid leukaemia progression |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 |
Compare the efficacy, measured as overall survival (OS), of elacytarabine and
investigator’s choice in patients with late stage AML |
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E.2.2 | Secondary objectives of the trial |
Compare response rate and duration of response of elacytarabine and investigator’s choice in patients with late stage AML
Compare the safety profile of elacytarabine with investigator’s choice
Characterize exposure-response relationships for measures of effectiveness and toxicity. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients must be 18 years of age or older
2. Patients with a confirmed diagnosis of AML according to WHO classification (excluding acute promyelocytic leukaemia) who have received 2 or 3 induction/re-induction regimen or patients of age ≥ 65 with adverse cytogenetic (see appendix 5 for complete list) who have received 1-3 previous induction/re-induction regimens. One of the (re-)induction regimens could be stem cell transplantation (SCT) for achievement of remission. Maintenance and consolidation (including SCT) may have been given, but are not counted as previous regimens.
3. Patient’s bone marrow aspirates and/or biopsies must contain > 5 % leukaemic blast cells or patient must have biopsy-proven extramedullary AML, or patient’s peripheral blood shows occurrence of leukaemic blast cells
4. Patients must
a. have never attained CR or CRi (primary refractory), or
b. have failed initial induction therapy, and have attained CR or CRi after salvage therapy(ies), and then relapsed within < 6 months, or
c. have attained CR or CRi after initial induction therapy and relapsed within <12 months, and failed to respond to salvage therapy(ies), or
d. have relapsed after the latest CR or CRi within < 6 months
5. Patients younger than 65 years should have received previous treatment with cytarabine
6. Patients must have recovered from previous bone marrow and/or stem cell transplantation to a stage that the patient can tolerate the study treatment. There is no restriction on number of regimens or type of treatment administered for maintenance or consolidation during previous stages of the disease
7. Patients must have ECOG performance status (PS) of 0 – 2
8. Women of child-bearing potential must have a negative serum or urine pregnancy test within 2 weeks prior to treatment start
9. Male and female patients must use acceptable contraceptive methods for the duration of time on study, and males also for 3 months after the last elacytarabine dose
10. Patients must be capable of understanding and complying with protocol requirements, and must be able and willing to sign a written informed consent form
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E.4 | Principal exclusion criteria |
1. A history of allergic reactions to egg. A history of allergic reactions of CTCAE grade 3 or 4 to cytarabine
2. Persistent clinically significant toxicities from previous chemotherapy
3. A cancer history that, according to the investigator, might confound the assessment of the study endpoints
4. Known positive status for human immunodeficiency virus (HIV)
5. Pregnant and nursing patients
6. Uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, or psychiatric illness/social situations that would limit compliance with study requirements
7. Impairment of hepatic or renal function to such an extent that the patient, in the opinion of the investigator, will be exposed to an excessive risk if entered into this clinical study
8. Active heart disease including myocardial infarction within previous 3 months, symptomatic coronary artery disease, arrhythmias not controlled by medication, or uncontrolled congestive heart failure. Any NYHA grade 3 or 4
9. Applicable only for patients for whom an anthracycline is part of the selected control treatment:
Left ventricular ejection fraction (LVEF) must be ≥ 45 % as measured by MUGA scan or 2D ECHO within 14 days prior to start of therapy. Either method is acceptable for measuring LVEF
10. Applicable only for patients for whom an anthracycline is part of the selected control treatment:
The patient should tolerate minimum one course of anthracycline containing therapy.
11. Patients receiving any anti-leukaemic agents within the last 3 weeks. Hydroxyurea, however, is allowed for up to 12 hours prior to study treatment.
12. Patients receiving any investigational treatment within the last 14 days
13. Any medical condition which in the opinion of the investigator places the patient at an unacceptably high risk for toxicities
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E.5 End points |
E.5.1 | Primary end point(s) |
Number of deaths from any cause |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Survival (Follow-up visit): For safety: 30 – 40 d after the last dose. For relapse and survival: monthly |
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E.5.2 | Secondary end point(s) |
1.- Remission rate measured by overall response rate (ORR); i.e. complete remission (CR) and complete remission with incomplete bone marrow recovery (CRi)
2.- Remission rate measured by CR
3.- Remission duration analysed using cumulative incidence of relapse (CIR) measured from date of CR or CRi
4.- Safety profile by assessing clinical and laboratory adverse events (AEs), and deaths
5.- Correlate PK profiles with response and toxicity |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1.- This can be assessed once the study is complete.
2.- Same as above.
3.- Same as above, complete data will be available only after the study is over and the follow-up period completed for all enrolled patients + all follow-up data is available.
4.- Same as above + Periodic assessment at IDMC – approx q 3 months and at the study end.
5.- At the study end once PK analysis is completed and all safety events are clarified so following database lock and clean database transferred to Clavis.
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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 | No |
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 | 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 |
Investigators´choice (There is no standard therapy for second salvage treatment of AML) |
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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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 48 |
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 |
Belgium |
Canada |
Germany |
Ireland |
Italy |
Poland |
Romania |
Spain |
United Kingdom |
United States |
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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 | 1 |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |