E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 10000886 |
E.1.2 | Term | Acute myeloid leukemia |
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 |
To compare anti-leukemic activity of allogeneic stem cell trans-plantation for patients with acute leukemia, in complete remis-sion between a 10/10 HLA matched unrelated donor and a haploidentical donor. |
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E.2.2 | Secondary objectives of the trial |
To assess and compare the safety and efficacy of study treat-ments therapy in both study arms on non-relapse mortality (NRM), relapse-free survival (RFS), Overall survival (OS), QOL, toxicity, development of acute and chronic GvDH as well as engraftment and chimerism and impact of measurable residual disease. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Acute Myeloid Leukemia (AML) intermediate or high risk according to ELN or Acute Lymphoblastic Leukemia (ALL) high risk according to ESMO guidelines in 1. CR or AML/ALL in 2. CR, or high risk MDS (according to IPSS-R) in 1. CR or 2. CR. 2. Patients age: 18 - 70 years at time of inclusion (female and male) 3. Patients understand and voluntarily sign an informed consent form 4. ECOG ≤ 2 5. 10/10 HLA-matched unrelated donor [9/10 mismatch is allowed if HLA mismatch is located in DQB1 (by high resolution typing)] and haploidentical (≥ 5/10 and ≤ 8/10 HLA) relative matched donor available at least 4 weeks after completion of induction and/or consolidation therapy. The mismatch related donor should not be older than 65 years of age. 6. Females/Males who agree to comply with the applicable contraceptive requirements of the protocol |
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E.4 | Principal exclusion criteria |
1. Severe renal, hepatic, pulmonary or cardiac disease, such as: - total bilirubin, SGPT or SGOT > 3 times upper the normal level - left ventricular ejection fraction < 30 % - creatinine clearance < 30 ml/min - DLCO < 35 % and/or receiving supplementary continuous oxygen 2. Positive serology for HIV 3. Pregnant or lactating women (positive serum pregnancy test) 4. Age < 18 and ≥ 71 years. 5. Uncontrolled invasive fungal infection at time of screening (baseline) 6. Serious psychiatric or psychological disorders 7. Participation in another study with ongoing use of unlicensed investigational product from 28 days before study enrollment 8. Uncontrolled severe autoimmune disease or uncontrolled other malignancy 9. Availability of an HLA-identical sibling as donor source |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Relapse incidence at two years between both arms |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline, Day 30, Day 100, 6 months, 12 months, 24 months |
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E.5.2 | Secondary end point(s) |
1. Overall survival at two years between both arms 2. Overall survival for all patients assigned to one of the two treatment arms as time to event endpoint 3. Comparison of GVHD/relapse-free survival as composite endpoint in both arms 4. Comparison of non-relapsed mortality (NRM) at 1 and 2 years after allogeneic SCT in both arms 5. Comparison of acute graft-versus-host disease (aGVHD) on day +100 and 1 year (max grade) after allogeneic SCT according to the Glucksberg scale revised by Przepiorka et al. between both arms 6. Comparison of chronic graft-versus-host disease (cGVHD) according to the NIH consensus criteria of Jagasia et al. at 1 and 2 years after allogeneic SCT between both arms 7. Comparison of toxicity of both regimens scored according to the current version of the NCI CTCAE between both arms 8. Comparison of immune reconstitution and full donor chimerism between both arms 9. Evaluation of Sorror Risk Score [8] (Appendix 13.1) on outcome after allogeneic SCT 10. Comparison of QOL (FACT-BMT) before and after transplantation at + 100 days, 6 months, 1 year, 2 years between both arms |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Baseline, Day 30, Day 100, 6 months, 12 months, 24 months |
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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 | No |
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.8.3 |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 31 |
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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The end of study is at the time when the EU Clinical Trial Directive 2001/20/EC is no longer valid, but latest on 30.01.2025 (LPLV). A transition of this study to the new EU Clinical Trial Regulation 536/2014 is not intended. |
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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 | 5 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 16 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 16 |