E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with a hematologic malignancy (AML, ALL, or MDS) who are eligible for a haploidentical HSCT. |
Pazienti con malignita' ematologiche (AML, ALL o MDS) che sono eleggibili per trapianto da cellule staminali (HSCT) da donatore aploidentico. |
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E.1.1.1 | Medical condition in easily understood language |
Patients with blood cancer who are eligible for a stem cell transplantation from a related haploidentical donor |
Pazienti con cancro del sangue che sono eleggibili per un trapianto di cellule staminali da donatore aploidentico. |
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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 | 22.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10059044 |
E.1.2 | Term | Allogeneic peripheral hematopoietic stem cell transplant |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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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 | 10000845 |
E.1.2 | Term | Acute lymphoblastic 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 | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10000880 |
E.1.2 | Term | Acute myeloid leukaemia |
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 | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10028533 |
E.1.2 | Term | Myelodysplastic syndrome |
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 | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10027703 |
E.1.2 | Term | Mismatched donor bone marrow transplantation therapy |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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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 study is to compare safety and efficacy of a haploidentical T cell depleted HSCT and adjunctive treatment with ATIR101 versus a haploidentical T cell replete HSCT with post-transplant administration of high dose cyclophosphamide (PTCy) in patients with a hematologic malignancy. An additional objective of the study is to compare the effect of the two treatments on quality of life. |
Comparare la sicurezza e l'efficacia di un HSCT aploidentico senza linfociti T e trattamento adiuvante con ATIR101, versus un HSCT aploidentico non manipolato con somministrazione post-trapianto di ciclofosfamide (PTCy) a dosi elevate in pazienti con tumore maligno ematologico. Un altro obiettivo dello studio e' quello di comparare l'effetto dei due trattamenti sulla qualita' della vita. |
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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 |
1. Any of the following hematologic malignancies: - Acute myeloid leukemia (AML) in first cytomorphological remission (with < 5% blasts in the bone marrow) with Disease Risk Index (DRI) intermediate or above, or in second or higher cytomorphological remission (with < 5% blasts in the bone marrow) - Acute lymphoblastic leukemia (ALL) in first or higher remission (with < 5% blasts in the bone marrow) - Myelodysplastic syndrome (MDS): transfusion-dependent (requiring at least one transfusion per month), or intermediate or higher IPSS-R risk group) 2. Clinical justification of allogeneic stem cell transplantation where a suitable HLA matched sibling or unrelated donor is unavailable in a timely manner. 3. Availability of a related haploidentical donor with one fully shared haplotype and 2 to 4 mismatches at the HLA-A, -B, -C, and -DRB1 loci of the unshared haplotype, as determined by high resolution HLA-typing 4. Karnofsky Performance Status (KPS) = 70% 5. Male or female, age = 18 years and = 70 years Patients aged = 65 years must have a Sorror score = 3 6. Patient weight = 25 kg and = 130 kg 7. Availability of a donor aged = 16 years and = 75 years who is eligible according to local requirements and regulations. Donors aged < 16 years are allowed if they are the only option for an HSCT, if they are permitted by local regulations, and if the IRB/IEC approves participation in the study. 8. For females of childbearing potential27 who are sexually active and males who have sexual contact with a female of childbearing potential: willingness to use reliable methods of contraception (oral contraceptives, intrauterine device, hormone implants, contraceptive injection or abstinence) during study participation 9. Given written informed consent (patient and donor) |
La popolazione dello studio consiste di pazienti maschi e femmine, di età compresa tra i 18 e i 70 anni, con malignità ematologica (AML in remissione, ALL in remissione o MDS) che sono eleggibili per un HSCT aploidentico. Il Performance Status secondo Karnofsky (KPS) deve essere maggiore o uguale al 70%. |
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E.4 | Principal exclusion criteria |
1. Diagnosis of chronic myelomonocytic leukemia (CMML) 2. Availability of a suitable HLA-matched sibling or unrelated donor in a donor search 3. Prior allogeneic hematopoietic stem cell transplantation 4. Diffusing capacity for carbon monoxide (hemoglobin corrected DLCO) < 50% predicted 5. Left ventricular ejection fraction < 45% (evaluated by echocardiogram or MUGA scan) 6. AST and/or ALT > 2.5 × ULN (CTCAE grade 2) 7. Creatinine clearance < 50 ml/min (calculated or measured) 8. Positive pregnancy test or breastfeeding of patient or donor (women of childbearing age only) 9. Estimated probability of surviving less than 3 months 10. Known allergy to any of the components of ATIR101 (e.g., dimethyl sulfoxide) 11. Known hypersensitivity to cyclophosphamide or any of its metabolites 12. Any contraindication for GVHD prophylaxis with mycophenolate mofetil, cyclosporine A, or tacrolimus 13. Known presence of HLA antibodies against the non-shared donor haplotype 14. Positive viral test of the patient or donor for HIV-1, HIV-2, HBV28, HCV28, Treponema pallidum, HTLV-1 (if tested), HTLV-2 (if tested), WNV (if tested), or Zika virus (if tested) 15. Any other condition that, in the opinion of the investigator, makes the patient or donor ineligible for the study |
1. Diagnosi di leucemia mielomonocitica cronica (CMML) 2. Disponibilità di un donatore con corrispondenza HLA 3. Precedente trapianto ematopoietico allogenico 4. DLCO < 50% del valore previsto 5. Frazione di eiezione < 45% 6. AST e/o ALT > 2.5 × ULN 7. Tasso di smaltimento della creatinina < 50 ml/min 8. Test di gravidanza positivo o paziente o donatore in allattamento 9. Sopravvivenza prevista inferiore ai 3 mesi 10. Controindicazione alla profilassi verso GVHD con micofenolato mofetile, ciclosporina A, o tacrolimus 11. Ricevente o donatore positivo a HIV-1, HIV-2, HBV, HCV, Treponema pallidum, HTLV-1 (se applicabile), HTLV-2 (se applicabile), WNV (se applicabile), or Zika virus (se applicabile) |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of the study is GVHD-free, relapse-free survival (GRFS). |
L'endpoint primario dello studio è la sopravvivenza libera da recidive e da GVHD (GRFS). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
GRFS is defined as time from randomization until grade III/IV acute GVHD, chronic GVHD requiring systemic immunosuppressive treatment, disease relapse, or death, whichever occurs first. |
La GRFS viene definita come il tempo dalla randomizzazione fino alla malattia acuta da trapianto contro ospite (GVHD) di grado II/III, alla GVHD cronica richiedente trattamento immunosoppressivo sistemico, alla recidiva della malattia o alla morte, a seconda di quello che compare prima. |
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E.5.2 | Secondary end point(s) |
1. Overall survival (safety and efficacy) 2. Progression-free survival (efficacy) 3. Relapse-related mortality (efficacy) 4. Transplant-related mortality (safety and efficacy) |
1. Sopravvivenza globale (OS) 2. Sopravvivenza libera da progressione (PFS) 3. Mortalita' correlata a recidiva (RRM) 4. Mortalita' correlata a trapianto (TRM) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Overall survival (OS) is defined as the time from randomization until death from any cause. 2. Progression-free survival (PFS) is defined as the time from randomization until relapse, disease progression, or death, whichever occurs first. 3. Relapse-related mortality (RRM) is defined as the time from randomization to death due to disease relapse or disease progression. 4. Transplant-related mortality (TRM) is defined as the time from randomization to death due to causes other than disease relapse or disease progression. |
1. Tempo dalla randomizzazione alla morte. 2. Tempo dalla randomizzazione alla ricaduta, progressione di malattia o morte (qualunque evento si verifichi per primo). 3 Tempo dalla randomizzazione alla morte a cause di ricaduta o progressione della malattia 4. Tempo dalla randomizzazione alla morte per cause diverse dalla ricaduta o progressione di malattia |
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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) | 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 | 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) | 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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
Canada |
Croatia |
France |
Germany |
Israel |
Italy |
Netherlands |
Portugal |
Spain |
Sweden |
United Kingdom |
United States |
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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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The end of the study is defined as the date at which the last data point from the last patient is received. |
La fine dello studio e' definita come la data nella quale sara' raccolto l'ultimo dato dell'ultimo paziente. |
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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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
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 |