Clinical Trials /

DC Vaccination for Postremission Therapy in AML

NCT01734304

Description:

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.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Completed

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: DC Vaccination for Postremission Therapy in AML
  • Official Title: Active Immunotherapy of Patients With Acute Myeloid Leukemia Using Autologous Dendritic Cells Transfected With RNA Encoding Leukemia-associated Antigens

Clinical Trial IDs

  • ORG STUDY ID: 2010-022446-24
  • NCT ID: NCT01734304

Conditions

  • Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
DC vaccination for postremission therapy in AMLDC vaccination

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
DC vaccinationExperimentalDC vaccination

    Eligibility Criteria

            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
          
    Maximum Eligible Age:75 Years
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:% of grade I/II and grade III/IV toxicities
    Time Frame:30 weeks
    Safety Issue:
    Description:

    Secondary Outcome Measures

    Measure:Immune responses to applied antigens
    Time Frame:30 weeks
    Safety Issue:
    Description:
    Measure:Control of minimal residual disease
    Time Frame:30 weeks
    Safety Issue:
    Description:
    Measure:Time to progression of disease
    Time Frame:30 weeks
    Safety Issue:
    Description:
    Measure:ECOG performance status
    Time Frame:30 weeks
    Safety Issue:
    Description:

    Details

    Phase:Phase 1/Phase 2
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Ludwig-Maximilians - University of Munich

    Trial Keywords

    • vaccination
    • postremission therapy
    • acute myeloid leukemia
    • dendritic cells

    Last Updated