E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Newly diagnosed high-risk AML other than acute promyelocytic leukemia, ≥20% blasts |
neu diagnostizierte AML (außer Promyelozytenleukämie); ≥20% Blasten |
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E.1.1.1 | Medical condition in easily understood language |
Newly diagnosed high-risk Acute Myeloid Leukemie |
neu diagnostizierte Akute Myeloische Leukämie |
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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 | 10000886 |
E.1.2 | Term | Acute myeloid leukemia |
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 |
To compare the efficacy of haploidentical NK-cell based consolidation with standard cytarabine based consolidation in elderly patients suffering from AML with high risk of fatal relapse and no option for allogeneic stem cell transplantation (SCT). |
|
E.2.2 | Secondary objectives of the trial |
- To compare the time to relapse (TTR), the cumulative incidence of relapse (CIR) and relapse-free survival (RFS) between the two study groups - To investigate the yield and purity of NK cells (CD3-CD56+) after CD3 de-pletion and CD56 enrichment - To investigate patients NC cell recovery, NK cell chimerism, NK phenotype and functional capacity of NK cells at various time points after infusion - To compare tolerability and safety of the two interventions |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Newly diagnosed AML other than acute promyelocytic leukemia (APL) according to WHO criteria, i.e. bone marrow aspirate or biopsy must have contained ≥20% blasts • Clinical performance corresponding to ECOG score 0-2 • High-risk karyotype • <5% myeloblasts in bone marrow ≥21 days after beginning of most recent chemotherapy • maximal two preceding chemotherapy cycles (either two induction cycles or one induction + one consolidation cycle) • Study inclusion (experimental or control intervention) latest 56 days after preceding chemotherapy • Reconstitution of peripheral blood leukocytes following chemotherapy (total leukocytes >1.5 GPT/l; neutrophil granulocytes >0.5 GPT/l) • No available HLA-matched (≥ 9 of 10 HLA-alleles) stem cell donor or unfit for allogeneic hematopoietic stem cell transplantation • Available haploidentical family donor, willing and fit for NK cell donation |
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E.4 | Principal exclusion criteria |
• AML with favorable risk cytogenetic features, i.e. t(15;17) or PML-RAR alpha transcript or t(8;21) or RUNX1 transcript or inv(16) or CBFa transcript • AML with t(9;11)(p22;q23) • AML with intermediate risk cytogenetic features, i.e. no high-risk cytogenetic features as defined in inclusion criteria and no favorable cyto-genetic features as defined in exclusion criteria, FLT3-ITD ratio ≤0.8 • Persistent aplasia following preceding chemotherapy • Relapsed or refractory AML • Available HLA-matched (≥9 of 10 HLA-alleles) stem cell donor and patient fit for allogeneic stem cell transplantation • Age <60 years • Known pre-existing autoimmune diseases • Any severe concomitant condition which makes it undesirable for the patient to participate in the study (e.g. end stage irreversible multi organ failure, HIV infection, uncontrolled active infections >°2 ) • Any condition which could jeorpadize compliance of the protocol • Participation in another clinical trial (investigational drug therapy outside of this trial) during or within 4 weeks before study entry |
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E.5 End points |
E.5.1 | Primary end point(s) |
2-year overall survival |
2 Jahres Gesamtüberleben |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
2-year after study inclusion |
2 Jahre nach Studieneinschluss |
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E.5.2 | Secondary end point(s) |
• Time to relapse (TTR), cumulative incidence of relapse (CIR), • Relapse-free survival (RFS), • Yield and purity of NK cells (CD3-CD56+) after CD3 depletion and CD56 enrichment, • Patient NK cell recovery • NK cell chimerism • NK phenotype s • Clinical performance (ECOG score) • Incidence and severity of GVHD • Incidence of AEs and SAEs |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
up to 2 years from study inclusion |
bis 2 Jahre nach Studieneinschluss |
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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 | 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) | No |
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 | 8 |
E.8.5 | The trial involves multiple Member States | No |
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 | 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
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |