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DC Vaccination for Postremission Therapy in AML

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ClinicalTrials.gov Identifier: NCT01734304
Recruitment Status : Completed
First Posted : November 27, 2012
Last Update Posted : October 12, 2018
Sponsor:
Information provided by (Responsible Party):
PD Dr. Marion Subklewe, Ludwig-Maximilians - University of Munich

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Biological: DC vaccination for postremission therapy in AML Phase 1 Phase 2

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  (Clinical Trial)
Actual Enrollment : 13 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Active Immunotherapy of Patients With Acute Myeloid Leukemia Using Autologous Dendritic Cells Transfected With RNA Encoding Leukemia-associated Antigens
Actual Study Start Date : November 5, 2013
Actual Primary Completion Date : March 31, 2018
Actual Study Completion Date : September 30, 2018


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




Primary Outcome Measures :
  1. % of grade I/II and grade III/IV toxicities [ Time Frame: 30 weeks ]

Secondary Outcome Measures :
  1. Immune responses to applied antigens [ Time Frame: 30 weeks ]
  2. Control of minimal residual disease [ Time Frame: 30 weeks ]
  3. Time to progression of disease [ Time Frame: 30 weeks ]
  4. ECOG performance status [ Time Frame: 30 weeks ]


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01734304


Locations
Germany
Hospital of the University of Munich, LMU; Department od Medicine III
Munich, Germany, 81377
Sponsors and Collaborators
Ludwig-Maximilians - University of Munich
Investigators
Principal Investigator: Marion Subklewe, PD Dr Department of Medicine III; Hospital of the University of Munich,

Responsible Party: PD Dr. Marion Subklewe, Prof. Dr. med. Marion Subklewe, Ludwig-Maximilians - University of Munich
ClinicalTrials.gov Identifier: NCT01734304     History of Changes
Other Study ID Numbers: 2010-022446-24
First Posted: November 27, 2012    Key Record Dates
Last Update Posted: October 12, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by PD Dr. Marion Subklewe, Ludwig-Maximilians - University of Munich:
vaccination
postremission therapy
acute myeloid leukemia
dendritic cells

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Vaccines
Immunologic Factors
Physiological Effects of Drugs