E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
AML, MDS, ALL, CML, CLL, NHL, HL, or a myeloproliferative disease (MPD) |
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E.1.1.1 | Medical condition in easily understood language |
Patients with a selected range of hematological malignancies eligible for allogeneic stem cell transplantation. |
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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 | 10000835 |
E.1.2 | Term | Acute leukemia |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 | 10008948 |
E.1.2 | Term | Chronic leukemia |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10068361 |
E.1.2 | Term | MDS |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10025319 |
E.1.2 | Term | Lymphomas Hodgkin's disease |
E.1.2 | System Organ Class | 10005329 - Blood and lymphatic system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10025321 |
E.1.2 | Term | Lymphomas non-Hodgkin's T-cell |
E.1.2 | System Organ Class | 10005329 - Blood and lymphatic system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10025320 |
E.1.2 | Term | Lymphomas non-Hodgkin's B-cell |
E.1.2 | System Organ Class | 10005329 - Blood and lymphatic system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10077465 |
E.1.2 | Term | Myeloproliferative neoplasm |
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 | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Primary objective is to address whether the individualized fludarabine conditioning reduces the incidence of severe viral infections at day 100 within the context of an αβTCR / CD19 depleted transplantation regimen. |
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E.2.2 | Secondary objectives of the trial |
Secundary objective is to address whether the individualized fludarabine conditioning affects other clinical transplantation-related parameters, variations in individual fludarabine exposures and immunological reconstitution after an alpha/beta TCR/CD19 depleted stem cell transplantation. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Adults (> 18 years) 2. AML, MDS, ALL, CML, CLL, NHL, HL, or a myeloproliferative disease (MPD) 3. Indication for allo-SCT according to the policy of the local center 4. WHO performance status ≤ 2 5. Written informed consent
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E.4 | Principal exclusion criteria |
1. Relapse of disease within 5 months after previous allo-SCT 2. Bilirubin and/or transaminases > 2.5 x normal value* 3. Creatinine clearance < 40 ml/min* 4. Cardiac dysfunction as defined by: - Unstable angina or unstable cardiac arrhythmias - NYHA classification > II (Appendix B) - Cardiac symptoms and/or history of cardiac disease AND a cardiac ejection fraction < 45% 5. Active, uncontrolled infection
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E.5 End points |
E.5.1 | Primary end point(s) |
Cumulative incidence of severe viral infections (> grade 2) until day 100 |
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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) |
- aGVHD until day 100 - NRM until day 100 - Number of graft failures until day 100 - Donor engraftment (chimerism > 95%) at day 100 - ATG exposure - Fludarabine exposure - Busulfan exposure - Time to neutrophil engraftment - Time to platelet engraftment - Immune reconstitution including but not limited to 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, assessment of NK and TCR repertoires at defined time points with personalized fludarabine conditioning. - Incidence of infections - Incidence and grade of chronic GvHD - Long term NRM (2Y) - Long term (secondary) graft failure (2Y) - Event free survival (EFS: i.e. time from transplantation until progression/relapse, graftfailure 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 - Graft composition (CD34+ cells, αβ T cells, γδ T cells, NK cells, B cells) - Cost effectiveness at 2Y
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Up to 2 years post alloSCT |
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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) | 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 | 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 |
Fludarabin based on classical dosing |
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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
| 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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
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
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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 | 4 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |