E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with aggressive hematological malignancies treated with allogeneic stem cell transplantation |
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E.1.1.1 | Medical condition in easily understood language |
Patients with aggressive hematological cancers treated with allogeneic stem cell transplantation |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
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 |
The primary objectives of our study are to evaluate safety, toxicity and capability of inducing T cell responses of vaccination with monocyte-derived donor DC electroporated with mRNA encoding hematopoietic-restricted MiHA in patients who had undergone allo-SCT with stem cells from HLA-matched, MiHA-mismatched donor. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective is to evaluate the clinical effect of vaccination in case of detectable minimal residual disease and mixed chimerism. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Patients with AML, myelodysplasia (MDS), ALL, CML (accelerated or blast phase), CLL, MM or malignant NHL, who underwent HLA-matched allo-SCT
• Patients positive for HLA-A2, HLA-A24, HLA-B7 and/or HLA-B44
• Patients positive for HA-1, LRH-1 and/or ARHGDIB transplanted with corresponding MiHA-negative donor
• Patients >18 and <65 years of age
• WHO performance 0-2
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E.4 | Principal exclusion criteria |
• Life expectancy < 3 months
• Severe neurological or psychiatric disease
• Progressive disease needing cytoreductive therapy
• HIV positivity
• Patients with acute GVHD grade 3 or 4
• Patients with extensive chronic GVHD
• Patients with active infections (viral, bacterial or fungal) that requires specific therapy. Acute anti-infectious therapy must have been completed within 14 days prior to study treatment
• Severe cardiovascular disease (arrhythmias requiring chronic treatment, congestive heart failure or symptomatic ischemic heart disease
• Severe pulmonary dysfunction (CTCAE III-IV)
• Severe renal dysfunction (serum creatinine > 3 times normal level)
• Severe hepatic dysfunction (serum bilirubin or transaminases > 3 times normal level)
• Patients with known allergy to shell fish
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary study parameters are to evaluate the safety, toxicity, development of GVHD and the immunological response by appearance of MiHA-specific CD8+ T cells following vaccination with monocyte-derived donor DC electroporated with mRNA encoding hematopoietic-restricted MiHA in patients who had undergone allo-SCT with stem cells from HLA-matched, MiHA-mismatched donor. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Participating patients will visit the outpatient clinic weekly or two-weekly for standard physical examination and blood sampling from the first DC vaccination until 4 and 12 weeks after vaccination, respectively. For follow-up, peripheral blood will be collected from patients pre-study, at day 0, 7, 14, 21, 28, 42, 63 and 84 during and after DC vaccinations. The total amount of blood that will be taken for study purposes will be maximally 282 ml in a three month period. Two extra bone marrow aspirations will be performed (day 42 and 84 after first DC vaccination). |
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E.5.2 | Secondary end point(s) |
The secondary study parameters are to evaluate the clinical effect of MiHA-DC vaccination in case of detectable minimal residual disease and mixed chimerism. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Participating patients will visit the outpatient clinic weekly or two-weekly for standard physical examination and blood sampling from the first DC vaccination until 4 and 12 weeks after vaccination, respectively. For follow-up, peripheral blood will be collected from patients pre-study, at day 0, 7, 14, 21, 28, 42, 63 and 84 during and after DC vaccinations. The total amount of blood that will be taken for study purposes will be maximally 282 ml in a three month period. Two extra bone marrow aspirations will be performed (day 42 and 84 after first DC vaccination). |
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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) | Yes |
E.7.1.1 | First administration to humans | Yes |
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 | 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) | 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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | No |
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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Last visit of the last subject is day 84 after start study last subject. |
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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 | 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 |