E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Pre-emptive therapy of acute graft versus host disease with prednisolone according to specific proteomic patterns after allogeneic hematopoietic stem cell transplantation. |
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E.1.1.1 | Medical condition in easily understood language |
Early Prednisolone therapy of acute bone marrow rejection according to specific proteins detected in urine after bone marrow transplantation. |
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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 | 16.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10018652 |
E.1.2 | Term | Graft versus host reaction |
E.1.2 | System Organ Class | 100000004870 |
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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 the efficacy of pre-emptive immunosuppressive treatment (2-2.5mg prednisolone/kg BW/day) versus placebo immediately when a positive acute Graft-versus-Host disease (aGvHD,grade II-IV) and a specific proteomic pattern is observed. |
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E.2.2 | Secondary objectives of the trial |
To test the efficacy of pre-emptive treatment of (1) severity of aGvHD, (2) allogeneic HSCT related mortality due to toxicitiy or infections, (3) overall survival, (4) incidence of leukemic relapses and (5) safety of pre-emptive treatment |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Written informed consent • All patients ≥ 18 years on day +7 (+/- 3) after 1st allo-HSCT • Patients transplanted for: acute myeloid or lymphoid leukemia in CR (<5% leukemic blast cells in the bone marrow) or PR (<20% leukemic blast cells in the bone marrow); myelodysplastic and/or myeloproliferative syndromes: untreated, CR, PR; lymphomas: PR; chronic myeloid leukemia: CP; chronic lymphatic leukemia: CR, PR; multiple myeloma: CR, PR; severe aplastic anemia at the time of allogeneic HSCT • aGvHD prophylaxis with any combination of the following: e.g. cyclosporin A (CsA), methotrexate (MTX), mycophenolic acid (MMF), tacrolimus, sirolimus, everolimus and others with or with-out immunosuppressive antibodies (e.g. anti-thymocyte globulin (ATG)) • Woman of childbearing potential must have a negative pregnancy test prior to HSCT • Sufficient contraceptive methods for men and women of reproductive age at the beginning of the study and during the study and consent of the patient to used a sufficient contraceptive method within 6 months after the end of the study. Permitted double contraceptive methods are implants, injection preparation, intrauterine devices, portal cap, sterilization, hysterectomy, condoms, spermicide, vasectomy and/or sexual abstinence.
Prior to randomization: • Positivity of aGvHD-specific proteomic pattern
(Patients enrolled, who can not be randomized, will be followed-up in the observational group).
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E.4 | Principal exclusion criteria |
• Patients after ≥ 2nd allo-HSCT • Patients transplanted in relapse of their underlying disease (AML, ALL: ≥20% leukemic blast cells in the bone marrow) • Transplantation with CD34+-enriched or ex vivo T-cell-depleted stem cells, transplantation from syngeneic or haploidentical or cord blood donors • Steroids as part of the acute GvHD prophylaxis • Pregnant or nursing women • Participation in an other therapeutic study within 30 days before and during this study
Prior to randomization: • Patients with acute GvHD grade II to IV • Acute renal failure (≥ 2x upper normal boundary of serum creatinine) • Serious, life-threatening infection at the time of sampling for aGvHD proteomic pattern • Relapse or progression of underlying disease
(Patients enrolled, who cannot be randomized, will be followed-up in the observational group).
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary study endpoint: Occurrence of aGvHD (≥ grade II) between time of randomization and 100 days after allo-HSCT. Death occurring between randomization and 100 days post allo-HSCT without aGvHD (≥ grade II) will be considered as treatment failure, equivalent to an aGvHD (≥ grade II) development.
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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) |
Secondary study endpoints: (1) Severity of aGvHD until day 100 after allo-HSCT, (2) all aGvHD (≥ grade II), (3) severity of all aGvHD, (4) transplant-related mortality (TRM), (5) overall survival, (6) occurrence of leukemic relapses and (7) infectious complications.
Additional scientific endpoints: To establish proteomic patterns specific for steroid-resistant aGvHD. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
(1) until 100 days after allo-HSCT (2)-(6) until end of follow-up period (100 days + 365 days) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | Yes |
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) | 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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | Yes |
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 | 11 |
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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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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
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 |