E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with high risk acute leukemia / MDS or relapse acute leukemia /MDS |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066481 |
E.1.2 | Term | Hematological malignancy |
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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 test feasibility and safety of alpha/betaT-/CD19 B-cell depleted allo-SCT in high risk or relapsed acute leukaemia / MDS followed by an innate donor lymphocyte infusion (iDLI)by assessing: ♦ Time to neutrophil engraftment ♦ Time to platelet engraftment ♦ Time to donor engraftment (chimerism >95%) ♦ Time to red blood cell transfusion independence ♦ Incidence and grade of acute GvHD ♦ Incidence and grade of chronic GvHD ♦ Ability to generate and apply an iDLI ♦ Incidence of infections ♦ Transplant related mortality (TRM)
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E.2.2 | Secondary objectives of the trial |
♦ Immune reconstitution by counting total number of CD3+ T cells, CD4+ and CD8+ subtyping of T cells, CD3-CD16/56+ (NK cells), T-cells at 3, 6, 12 and 24 months after transplantation ♦ Progression free survival (PFS, i.e. time from transplantation until progression/relapse or death from any cause, whichever comes first) ♦ Overall survival (OS) calculated from transplantation. Patients still alive or lost to follow up are censored at the date they were last known to be alive
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
4.1 Inclusion criteria ♦ Age 18-65 years ♦ Meeting the criteria for a allo-SCT and high risk disease * (see below) ♦ WHO performance status ≤ 2 •Written informed consent
*High risk disease as defined by: ♦ AML with monosomal karyotype, abnormal 3q26, t(9;22) EVI-1-expression, or complex karyotype in first CR •No CR after first induction cycle chemotherapy ♦ Relapsed AML (in case of second allo-SCT if relapse occurs 6 months after allo-SCT) in second or subsequent CR ♦ MDS with complex karyotype or -7, transfusion dependent or neutropenic with < 10% blasts or in CR after induction therapy. • ALL with t(9;22), t(4;11), and other 11q23 abnormalities, and hypodiploidy; complex abnormalities (≥ 5), excluding hyperdiploidy; high WBC at diagnosis (B-ALL > 30x109/l, T-ALL > 100x109/l) in first CR, or no CR after first induction but in CR after rescue chemotherapy ♦ Relapsed ALL (in case of second allo-SCT if relapse occurs 6 months after allo-SCT) in second or subsequent CR
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E.4 | Principal exclusion criteria |
4.2 Exclusion criteria ♦ Relapse of allo-SCT within 6 months after allo-SCT ♦ Relapse acute promyelocyten leukemia ♦ Bilirubin and/or transaminases > 2.5 x normal value ♦ Creatinine clearance < 40 ml/min ♦ Cardiac dysfunction as defined by: Unstable angina Unstable cardiac arrhythmias ♦ Active, uncontrolled infection ♦ HIV positivity
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E.5 End points |
E.5.1 | Primary end point(s) |
7.1.1 Main study endpoints ♦ Time to neutrophil engraftment ♦ Time to platelet engraftment ♦ Time to donor engraftment (chimerism >95%) ♦ Time to red blood cell transfusion independence ♦ Incidence and grade of acute GvHD ♦ Incidence and grade of chronic GvHD ♦ Ability to generate and apply an iDLI ♦ Incidence of infections ♦ Transplant related mortality (TRM)
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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) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
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 | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 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 | Information not present in EudraCT |
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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1 year after allogeneic stem cell transplantation, or death. |
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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 | 6 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |