The aim of this study is to determine the feasibility and safety of an autologous DC
immunotherapy in patients with AML of non-favorable risk profile.
Patients ≥ 18 years of either gender with AML of non-favorable risk profile in CR or CRi not
being eligible for allogeneic stem cell transplantation will receive as intradermal
injections at two different sites up to ten immunotherapies with autologous DCs presenting
two leukemia-associated antigens and one CMV antigen conserved in cryomedium over a time span
of 26 weeks. Phase I will test the safety and toxicity in a small group of patients (n=6).
After at least four vaccinations of three patients, the safety and toxicity data will be
presented to the Data safety monitoring board (DSMB). Only after the DSMB has no objectives
against the continuation of the trial, further patients will be included into the trial.
Again, after three more patients, receiving a minimum of four vaccines, clinical data will be
presented to the DSMB, and phase I will be terminated. The decision for continuation of the
trial will be done by the DSMB. If there are no objectives by the DSMB, the trial will
continue and evaluation will be started in a larger group of patients (n=14). During the
phase II trial, safety and toxicity will be evaluated in a larger co-hort of patients).
Besides, preliminary assessment of efficacy will be performed including induction of
immunological responses to leukemia associated antigens as well as to a viral antigen (CMV),
MRD control, time to progression of disease and ECOG performance status.
Inclusion Criteria:
- Patients male or female, age ≥ 18 years, biological age ≤ 75 years
- Patients with AML of non-favorable risk profile or with AML 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 chemotherapy (TAD, HAM, sHAM, 3+7 anthracycline +
cytarabine regimen, or equivalent)
- Negative HIV test, negative hepatitis B and C test
- Negative pregnancy test in women of childbearing potential
- Ability to understand and willingness to sign a written informed consent
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
- Anemia (Hb < 9,0 mg/dl)
- Leukopenia (< 4,0 G/l)
- Transfusion refractory thrombocytopenia (< 30 G/l platelets despite adequate number of
transfusions)
- Active clinically relevant autoimmune disease
- Active immunodeficiency syndromes
- Known allergy to GM-CSF, TNF, IFN-γ, IL-4, IL-1 beta, PGE2, R848, Human AB Serum,
DMSO, HSA
- 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
failure > 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
Exclusion criteria regarding special restrictions for females:
- Current or planned pregnancy or nursing women
- Females of childbearing potential, who are not using and not willing to use medically
reliable methods of contraception for the entire study duration and at least 3 months
thereafter (such as oral, injectable, or im-plantable contraceptives, or intrauterine
contraceptive devices) unless they are surgically sterilized/hysterectomized or there
are any other criteria considered sufficiently reliable by the investigator in
individual cases
