E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Male and female patients with AML of non-favorable risk profile not eligible for allogeneic stem cell transplantation |
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E.1.1.1 | Medical condition in easily understood language |
In AML bone marrow infiltration through myeloid blasts leads to insufficient function of leukocytes and low numbers of platelets and hemoglobin leading to life-threatening complications within days. |
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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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10000878 |
E.1.2 | Term | Acute myeloblastic leukemia |
E.1.2 | System Organ Class | 100000004864 |
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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 |
Feasibility and safety of active immunotherapy with autologous DCs |
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E.2.2 | Secondary objectives of the trial |
- Induction of immune responses
- Control of minimal residual disease (MRD)
- Clinical response: time to progression (TTP)
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Patients male or female, age ≥ 18 years, biological age ≤ 75 years
- Patients with AML of non-favorable risk profile or wit hAML and sole NPM1 mutation and confirmed increase of MRD load as detected by RQ-PCR (in two measurements at least four weeks apart)
- CR or CRi, after intensive induction chemo-therapy (TAD, HAM, sHAM, 3+7 anthracycline + cytarabine regimen, or equivalent)
- No concomitant chemotherapy until week 6 (minimum completion of 4 DC injections)
- Negative HIV test (Anti-HIV-1,2-Ab), negative hepatitis B (HBs-Ag, Anti-HBc-Ab) and C (Anti-HCV-Ab) test (obtained within 7 days prior to study inclusion)
- Negative pregnancy test in women of childbearing potential (obtained within 7 days prior to study inclusion)
- Ability to understand and willingness to sign a written informed consent |
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E.4 | Principal exclusion criteria |
- Patients suitable for allogeneic HSCT (indication for allogeneic HSCT, adequate donor, no contraindication for allogeneic HSCT)
- Patients with AML with favorable risk profile:
- APL (AML M3)
- inv(16), t(16;16), or del(16) as sole anomaly
- t(8;21) as sole anomaly
- biallelic CEBPA mutation as sole anomaly
- NPM1 mutation as sole anomaly, unless with confirmed increase of MRD load
- Prior allogeneic HSCT
- Leukopenia (< 4,0 G/l)
- Anemia (Hb<9,0 g/dl)
- Transfusion refractory thrombocytopenia (< 30 G/l platelets despite adequate number of transfusions); patients with thrombcytopenia between 30 and 50 G/l are required to be treated as inpatients
- Active clinically relevant autoimmune disease
- Active immunodeficiency syndromes
- Known allergy to GM-CSF, TNF, IFN-γ, IL-4, PGE2, IL-1β, R848, human serum albumin, pooled human AB serum, DSMO, DPBS,or RPMI 1640
- Continuous therapy with corticosteroids or other immunosuppressive drugs during the trial
- Present substance abuse or any other factor that could limit the subject’s ability to comply with study procedures
- Severe organ dysfunction:
- Creatinine > 2,5 mg/ml
- Bilirubin > 3,0 mg/ml
- ALAT and ASAT > 3 x upper normal limit
- Respiratory insufficiency with pO2 < 60 mmHg
- Clinically relevant coronary heart disease of ventricular arrhythmia, congestive heart fail-ure > grade II NYHA
- Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study
- Simultaneous participation in another clinical trial or participation in any clinical trial involving an investigational medicinal product within 30 days prior to written informed consent for this trial |
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E.5 End points |
E.5.1 | Primary end point(s) |
1) % of grade I/II and grade III/IV toxicities
2) % of patients in whom treatment with the scheduled number of immu-notherapies (10 DC vaccinations) is feasible |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1) At all visits (V1-V10 + EOS)
2) At EOS |
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E.5.2 | Secondary end point(s) |
1) Immune responses to applied antigens
2) Control of minimal residual disease
3) Time to progression of disease
4) ECOG performance status |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) At all visits (V1-V10 + EOS)
2) At V5, V6, V7, V9 and EOS
3) At EOS
4) At all visits (V1-V10 + EOS) |
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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 | Yes |
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 | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
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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 | No |
E.8.1.2 | Open | No |
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
| 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 | 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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End of the trial ist when the last patient has finished the last visit |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |