E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated | |
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 | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10024349 |
E.1.2 | Term | Leukemia myeloid |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10024330 |
E.1.2 | Term | Leukemia acute |
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 objective of this trial is to compare outcome of two treatment strategies for patients with high-risk AML who failed to achieve or maintain a complete remission with standard therapy. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Signed written informed consent. -Male and female patients of 18 to 75 years of age. -Diagnosis of AML according to WHO criteria. -Patient is fit for aggressive induction chemotherapy and transplantation by assessment of an experienced hematologist. - No known history of chronic pulmonary disease and absence of dyspnea. Otherwise, documented diffusion lung capacity for carbon monoxide (DLCO) ≥40% (adjusted for hemoglobin, if available) and FEV1/FVC ≥ 50%. -HLA-identical sibling. or HLA-compatible unrelated donor (≥9/10 antigens matched for HLA-A, -B, -C, -DRB1, and –DQB1) with completed confirmatory typing or Two unrelated donors with >90% probability of 9/10 match for HLA-A, -B, -C, -DRB1, and –DRQB1, according to OptiMatch® list. --Relapse patients: -First AML relapse, defined as ≥5% bone marrow blasts and / or extramedullary AML manifestation. --Poor-responders : with ≥5% bone marrow blasts after the first cycle of induction therapy, and one of the following subtypes/risk groups of AML: -AML that evolves from previously documented myelodysplastic syndrome (MDS), or after a Myeloproliferative Neoplasia (MPN) or Diagnosis of therapy-related myeloid neoplasm (t-MN)or - Non favourable risk AML according to ELN-criteria |
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E.4 | Principal exclusion criteria |
-Acute promyelocytic leukemia (APL). WBC count of ≥50 GPt/L at study inclusion. -For poor-responder patients the first cycle of induction therapy contained HDAC, defined as cytarabine at single-doses of >1g/ m2. -Patient has received more than 440 mg/m2 daunorubicin equivalents -Severe organ dysfunction, defined as any of the following: oLeft ventricular ejection fraction <50%. oPatients who receive supplementary continuous oxygen. oSerum bilirubin >1.5 x ULN (if not considered Gilbert-Syndrome), or ASAT/ALAT >5 x ULN. oEstimated GFR < 50 ml/min. -Treatment with any investigational drug within 10 days before study entry. -Uncontrolled infection at the time of enrollment. -History of allogeneic transplantation. -Manifestation of AML in the central nervous system. -Pregnant or breast-feeding women. -Men unable or unwilling to use adequate contraception methods from start of study treatment to minimum of six months after the last dose of chemotherapy. -Women with childbearing potential except those who fulfill the following criteria: Post-menopausal or post-operative or continuous and correct application of a contraception method with a Pearl Index < 1 % or sexual abstinence or vasectomy of the sexual partner.
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E.5 End points |
E.5.1 | Primary end point(s) |
disease-free survival on day 56 after allogeneic stem cell transplantation. This composite endpoint consists of two major components: i) To have received allogeneic HCT within 16 weeks after randomization and; ii) to be free of disease on 56 days after HCT. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Overall survival by treatment arm is the most important secondary endpoint. In addition the rate of allogeneic stem cell transplantation, cumulative incidence of CR, and leukemia-free survival will be assessed by treatment arm. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
OS cumulative incidence until min. 2 years after randomization Rate of HCT at 4, 8 and 16 weeks CR cumulative incidence at 4, 8 and 24 weeks. LFS |
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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) | 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 | 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 | 18 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 18 |
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 | 6 |
E.8.9.1 | In the Member State concerned days | |
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 | 6 |