E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with hematologic malignancies who are eligible for an allogeneic stem cell transplantation but without the availability of matched related or unrelated donor within 1 - 3 months of initiation of a donor search (to be detemined by the investigator) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10009015 |
E.1.2 | Term | Chronic myeloid leukemia |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10000845 |
E.1.2 | Term | Acute lymphoblastic leukemia |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10063625 |
E.1.2 | Term | Acute lymphoblastic leukemia recurrent |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066110 |
E.1.2 | Term | T-cell lymphoblastic leukemia acute |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10000886 |
E.1.2 | Term | Acute myeloid leukemia |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10000887 |
E.1.2 | Term | Acute myeloid leukemia in remission |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025310 |
E.1.2 | Term | Lymphoma |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028533 |
E.1.2 | Term | Myelodysplastic syndrome |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028228 |
E.1.2 | Term | Multiple myeloma |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028233 |
E.1.2 | Term | Multiple myeloma without mention of remission |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008948 |
E.1.2 | Term | Chronic leukemia |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10028578 |
E.1.2 | Term | Myeloproliferative disorders (excl leukaemias) |
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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 study effects of the administration of donor lymphocytes depleted of allo-reactive T-cells (ATIR) to patients with hematologic malignancies on 6 months and 12 months transplant related mortality (TRM). |
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E.2.2 | Secondary objectives of the trial |
• To study the effects of ATIR on the incidence and severity of acute GvHD. • To study the effects of ATIR on the incidence and severity of chronic GvHD. • To study the effects of ATIR on Progression Free Survival (PFS) and Overall Survival (OS). • To study the effects of ATIR on the incidence and severity of bacterial, viral or fungal infections. • To study the effects of ATIR on immune reconstitution. • To study the effects of ATIR on the health status of patients (including Quality of Life [QoL]). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Recipient Inclusion Criteria (any of the following) Group 1: Primary Indications • Acute Myeloid Leukemia (AML): AML in first remission with high risk features (secondary AML, FLT-3 mutation, complex karyotype, abn(3q), -5/5q-, -7/7q-, abn(12p), abn(17p), or other cytogenetic anomaly of similar poor prognosis, or need for 2 induction regimens to achieve a complete remission (CR)). All AML in second emission. • Acute Lymphoblastic Leukemia (ALL): ALL in first remission with high-risk features (presenting leukocyte count > 30,000/mm3, karyotypes t(9;22), t(11;19), and t(4;11) biphenotypic leukemia, pro-B-ALL, late CR after induction therapy, T-ALL, rising MRD markers). All ALL in second remission. • Myelodysplastic Syndrome (MDS): Transfusion dependent MDS in IPSS risk group ‘int 1’ (0.5-1.0). • Ph-positive chronic myeloid leukemia (CML): Patients with CML in first chronic phase (CP) who have failed (either resistant or intolerant) at least 2 tyrosine kinase inhibitors.
Group 2: Secondary Indications • AML: All AML not belonging to Group 1 in subsequent remission or with evidence of chemo-sensitive disease. Patients with AML in hematologic remission who relapsed more than 2 years after allogeneic stem cell transplantation. • ALL: All ALL not belonging to Group 1 in subsequent remission or with evidence of chemo-sensitive disease. Patients with ALL in hematologic remission who relapsed more than 2 years after allogeneic stem cell transplantation. • Non-Hodgkin Lymphoma (NHL): All high grade and low grade Non-Hodgkin lymphoma (other than CLL and MM) in 2nd or 3rd remission (at least PR) after standard of care treatments including autologous stem cell transplantation concurrently not featuring bulky disease (defined as lymphomas ≥ 5 cm). • Myelodysplastic Syndrome (MDS): MDS in IPSS risk group ‘int 2’ (score 1.5-2.0). MDS in IPSS risk group ‘high’ (score ≥ 2.5). Patients with more than 20% blasts in the marrow will be considered AML. • Chronic Myeloid Leukemia (CML): Patients with CML in second or later chronic phase. Patients with blast crisis will be considered AML. Patients with accelerated phase will be excluded. • Multiple Myeloma (MM): Secretory MM with or without osteolytic lesions concurrently not featuring extramedullary disease responsive to prior autologous stem cell transplantation(s) or at least one standard of care treatment (defined as 50% reduction of paraprotein in serum/plasma and/or 75% reduction of paraprotein in urine). • Chronic Lymphocytic Leukemia (CLL): CLL requiring treatment (Binet C or A/B with “active disease” according to the NCI criteria) and refractory to or progressive after a previous fludarabine- or equivalent purine-based regimen. These patients must at least achieve a partial remission. CLL transformed to high grade lymphoma (Richter transformation) will be excluded. • Myeloproliferative Syndrome (MPS): Myeloproliferative disorders in transformation to acute leukemia or with progressive transfusion requirements or pancytopenia including atypical (Ph negative) chronic myeloid and neutrophilic leukemias, progressing myelofibrosis, and polycythemia vera, essential thrombocythemia. Patients with more than 20% blasts in the marrow will be considered AML.
Other Inclusion Criteria • Male or female, age ≥ 18, ≤ 65 years. • Ability to comprehend the investigational nature of the study and provide informed consent. |
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E.4 | Principal exclusion criteria |
Recipient Exclusion Criteria (any of the following) • AML in 1st CR with good risk karyotypes: AML M3 (t15; 17), AML M4Eo (inv 16), AML t (8; 21) • MM featuring concurrent extramedullar disease or being non-responsive to prior therapy • CML featuring concurrent accelerated phase or blast crisis • CLL concurrently transformed into high-grade lymphoma • NHL with concurrent bulky disease (>= 5 cm) • DLCO < 40% predicted. • Left ventricular ejection fraction < 40% (evaluated by ECHO or MUGA). • AST/SGOT > 2.5 x ULN (CTCAE grade II v3.0). • Bilirubin > 1.5 x ULN (CTCAE grade II v3.0). • Creatinine > 1.5 x ULN (CTCAE grade II v 3.0). • HIV positive (Recipients who are positive for hepatitis B (HBV), hepatitis C (HCV) or human T-cell lymphotropic virus (HTLV-I/II) are not excluded from participation). • Positive pregnancy test for women of childbearing age. • Prior haploidentical PBSC or cord blood transplantation. • Less than 2 years from a prior allogeneic stem cell transplantation • Estimated probability of surviving less than three months. • Major anticipated illness or organ failure incompatible with survival from transplant. • Severe psychiatric illness or mental deficiency sufficiently severe as to make compliance with the transplant treatment unlikely and informed consent impossible. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Incidence of TRM at 6 months and 12 months after the transplantation. |
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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 | 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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
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.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
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 |
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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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In total 60 evaluable patients will be treated with ATIR. Patients who die due to progression or relapse prior to 6 or 12 months will not be considered evaluable and will be replaced. The trial ends when the last patient of the 60 patients that will be treated with ATIR and will survive the first 12 months, has been followed up for 24 months. |
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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 | 3 |
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 | 3 |
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 |