E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute myeloid leukemia
AML |
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E.1.1.1 | Medical condition in easily understood language |
Acute myeloid leukemia
AML |
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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 | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10001941 |
E.1.2 | Term | AML |
E.1.2 | System Organ Class | 100000004864 |
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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 |
The primary objective of this study is to assess the feasibility (safety and efficacy) of addition of
10-day decitabine to the standard Seattle non-myeloablative conditioning regimen (3 days
fludarabine 30 mg/m2 + 2 Gray TBI) prior to allogeneic HCT in poor and very poor risk AML
patients in CR1.
Safety will be assessed by adverse events and laboratory parameters; efficacy will be assessed by
(decrease of) relapse rate at 15 months (fixed time point) after last-patient-in. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are:
1. To assess the safety profile: i.e. treatment related mortality (TRM) of the transplantation
procedure and toxicity, associated with this conditioning regimen.
2. To assess transplant related parameters: i.e. acute and chronic graft-versus-host disease (GVHD),
rejection, engraftment kinetics (T-cell and bone marrow chimerisms).
3. To assess the efficacy profile: i.e. relapse frequency after allogeneic HCT, overall survival (OS),
disease free survival (DFS) and event free survival (EFS)
4. To assess the social/economic impact both therapy regimens: i.e. Quality of Life (QoL) (EORTCQ30;
t=0 and follow up), days staying in the hospital and transfusion needs.
5. To assess the impact of this conditioning regimen on mucositis (citrulline levels as biomarker of
intestinal mucositis) and conditioning-induced inflammation (soluble TNFR1, IL-8 and C-reactive
protein levels). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria
• Patients eligible for allogeneic HCT, independent of age
• Patients of any age with a cytopathologically confirmed diagnosis according to WHO classification of newly diagnosed AML (not APL = AML-M3), de novo AML or secondary AML
• in first complete remission (CR1)
• Poor risk or very poor risk subgroups
• WHO performance status ≤ 2
• Written informed consent
Poor risk is defined as: - Normal karyotype, WBC ≤ 100, not in CR after first cycle of chemo
- Normal karyotype, WBC > 100
- Abnormal karyotype, non CBF, MK, no abn 3q26, EVI1-
Very poor risk is defined as: - Non CBF, MK+
- Non CBF, abn eq26
- Non CBF, EVI1+
- Non CBF, high Flt3-ITD allelic burden
CBF = Core Binding Factor
MK = monosomal karyotype
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E.4 | Principal exclusion criteria |
Exclusion criteria
• Patient not in CR1
• Patients who have senile dementia, mental impairment of any other psychiatric disorder that prohibits the patient from understanding and giving informed consent
• Active serious infections like HIV, HBV and HCV
• Patient is unwilling to use contraceptive techniques during and for 12 months following treatment
• Female patient who is pregnant or breastfeeding
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E.5 End points |
E.5.1 | Primary end point(s) |
• Primary endpoints
• Relapse at 1-year after the transplantation procedure
• TRM at 1-year after the transplantation procedure
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
See before, this is defined in the endpoints |
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E.5.2 | Secondary end point(s) |
• Secondary endpoints
• Relapse within the first 100 days after the transplantation procedure
• TRM within the first 100 days after the transplantation procedure
• Grade II-IV and grade III-IV acute GVHD within the first year after the transplantation procedure
• Chronic GVHD at 1 year after the transplantation procedure
• Rejection within the first year after the transplantation procedure
• Overall survival (OS) (based on intention to treat analysis)
• Disease free survival (DFS), event free survival (EFS)
• Cumulative incidence of relapse
• Days of staying in hospital and transfusion needs
• Evolution of donor T cell chimerism levels
• TNFR1 and citrulline increment from the start of the conditioning regimen to day 7 after transplantation?
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
See before, this is defined in the endpoints |
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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 | 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) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
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 | No |
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.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
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 | No |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
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 | 5 |
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 |