Clinical trial NCT02405338: DC Vaccination for Post-remission Therapy in AML
Official title: Dendritic Cell-based Active Immunotherapy of Patients With Acute Myeloid Leukemia Using Autologous Cells Transfected With RNA Encoding Two Different Leukemia-associated Antigens
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Acute Myeloid Leukemia
Keywords: AML
Lead sponsor: Medigene AG
Sponsor class: INDUSTRY
First posted: 2015-04-01
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a multi-centre, open label, prospective, non-randomized phase I/II trial in 20 patients including a safety-run in phase I part comprising 6 patients.

Trial subjects will receive repeated immunotherapies with autologous Dendritic Cells (DCs), presenting two leukemia-associated antigens.

Detailed description: 20 patients with AML who are in remission (ELN criteria by Döhner et al 2017) receive WT1/PRAME autologous DC vaccine by intradermal injection once per week during the first 4 weeks and 1 per month thereafter for 23 consecutive months.

Primary objective is to assess the safety and tolerability of the DC vaccine in the aforementioned population and the feasibility.

Secondary objectives include evaluation of clinical response and exploratory immune monitoring assessments.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of Acute Myeloid Leukemia (AML)
* Age 18 - 75 years
* Morphologic remission (CR) with or without hematological recovery (CRi) following induction chemotherapy
* WT1 with or without PRAME positivity by qPCR
* Negative pregnancy test in women of childbearing potential (within 7 days before the first vaccination). Women of childbearing potential and sexually active male participants must use reliable methods of contraception during the whole treatment period and 3 months after the last trial drug dose
* Negative HIV 1 and 2 test, Hepatitis B and C test and negative Syphilis test at screening
* Informed consent signed prior to any trial related activities

Exclusion Criteria:

* Patients suitable for allogeneic stem cell transplantation
* AML M3 (acute promyelocytic leukemia)
* Patients not in complete remission (CR or CRi), bone marrow blast count ≥ 5 %
* Active immunodeficiency syndromes
* Concurrent active second malignancy other than non-melanoma skin cancers
* Clinically relevant autoimmune disease
* Prior immunotherapy
* Severe organ dysfunction precluding the apheresis procedure:
* Creatinine \> 200 mmol/l
* Bilirubin, 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
* Recent cerebral hemorrhage
* Known allergies to substances used in the generation of DCs
* Other severe acute or chronic medical psychiatric condition or laboratory abnormality that may increase the risk associated with trial participation or the administration of the investigational product
* Use of corticosteroids
* Active CMV infection (Antibody-positivity due to previous, now inactive infection is accepted)
* Inability to comply with the trial protocol
* Participation in other clinical trials that, according to the investigator's discretion, may interfere with this trial

Primary outcomes:
measure: Percentage of patients in whom treatment with the scheduled number of immunotherapies is feasible
timeFrame: 2 years
measure: Percentage of grade I/II, grade III/IV and grade ≥III toxicities in patients having received at least 1 immunotherapy
timeFrame: 2 years
Secondary outcomes:
measure: Overall survival
timeFrame: 2 years
measure: Relapse/Progression free survival
timeFrame: 2 years
measure: Time to progression (TTP).
timeFrame: 2 years
measure: Control of minimal residual disease (MRD)
timeFrame: 2 years
measure: ECOG performance status
timeFrame: 2 years
measure: Cellular immune responses to applied antigens
timeFrame: 2 years
Other outcomes:
Locations:
city: Oslo
country: Norway
facility: Oslo University Hospital, Rikshospitalet
Study officials:
affiliation: Oslo University Hospital, Rikshospitalet Department of Hematology
name: Yngvar Fløisand
role: PRINCIPAL_INVESTIGATOR
References: