DC Vaccination for Postremission Therapy in AML

Active Immunotherapy of Patients With Acute Myeloid Leukemia Using Autologous Dendritic Cells Transfected With RNA Encoding Leukemia-associated Antigens

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.

Study Overview

• Status: Completed
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Biological: DC vaccination for postremission therapy in AML

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Germany
  • Munich, Germany, 81377
    • Hospital of the University of Munich, LMU; Department od Medicine III

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DC vaccination; Vaccination with TLR7/8-matured DCs electroporated with mRNA encoding WT1, PRAME, and CMVpp65	Biological: DC vaccination for postremission therapy in AML; Vaccination with TLR7/8-matured DCs electroporated with mRNA encoding WT1, PRAME, and CMVpp65

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
% of grade I/II and grade III/IV toxicities	30 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Immune responses to applied antigens	30 weeks
Control of minimal residual disease	30 weeks
Time to progression of disease	30 weeks
ECOG performance status	30 weeks

Collaborators and Investigators

• Sponsor: Ludwig-Maximilians - University of Munich
• Investigators: Principal Investigator: Marion Subklewe, PD Dr, Department of Medicine III; Hospital of the University of Munich,

Publications and helpful links

General Publications

• Lichtenegger FS, Schnorfeil FM, Rothe M, Deiser K, Altmann T, Bucklein VL, Kohnke T, Augsberger C, Konstandin NP, Spiekermann K, Moosmann A, Boehm S, Boxberg M, Heemskerk MH, Goerlich D, Wittmann G, Wagner B, Hiddemann W, Schendel DJ, Kvalheim G, Bigalke I, Subklewe M. Toll-like receptor 7/8-matured RNA-transduced dendritic cells as post-remission therapy in acute myeloid leukaemia: results of a phase I trial. Clin Transl Immunology. 2020 Mar 3;9(3):e1117. doi: 10.1002/cti2.1117. eCollection 2020.

Study record dates

Study Major Dates

• Study Start (Actual): November 5, 2013
• Primary Completion (Actual): March 31, 2018
• Study Completion (Actual): September 30, 2018

Study Registration Dates

• First Submitted: October 17, 2012
• First Submitted That Met QC Criteria: November 22, 2012
• First Posted (Estimate): November 27, 2012

Study Record Updates

• Last Update Posted (Actual): October 12, 2018
• Last Update Submitted That Met QC Criteria: October 10, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: vaccination; acute myeloid leukemia; dendritic cells; postremission therapy
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
• Other Study ID Numbers: 2010-022446-24

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided