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DC Vaccination for Postremission Therapy in AML

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by Ludwig-Maximilians - University of Munich
Sponsor:
Information provided by (Responsible Party):
PD Dr. Marion Subklewe, Ludwig-Maximilians - University of Munich
ClinicalTrials.gov Identifier:
NCT01734304
First received: October 17, 2012
Last updated: December 2, 2013
Last verified: December 2013
  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.


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

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Ludwig-Maximilians - University of Munich:

Primary Outcome Measures:
  • % of grade I/II and grade III/IV toxicities [ Time Frame: 30 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Immune responses to applied antigens [ Time Frame: 30 weeks ] [ Designated as safety issue: No ]
  • Control of minimal residual disease [ Time Frame: 30 weeks ] [ Designated as safety issue: No ]
  • Time to progression of disease [ Time Frame: 30 weeks ] [ Designated as safety issue: No ]
  • ECOG performance status [ Time Frame: 30 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: September 2013
Estimated Study Completion Date: April 2019
Estimated Primary Completion Date: April 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: DC vaccination
DC vaccination
Biological: DC vaccination for postremission therapy in AML
.DC vaccination

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01734304

Contacts
Contact: Marion Subklewe, PD Dr +49897095 ext 3041 marion.subklewe@med.uni-muenchen.de
Contact: Felix Lichtenegger, Dr +49897095 ext 3041 Felix.Lichtenegger@med.uni-muenchen.de

Locations
Germany
Hospital of the University of Munich, LMU; Department od Medicine III Recruiting
Munich, Germany, 81377
Contact: Marion Subklewe, PD Dr    +49897095 ext 3041    marion.subklewe@med.uni-muenchen.de   
Contact: Felix Lichtenegger, Dr    +49897095 ext 3041    Felix.Lichtenegger@med.uni-muenchen.de   
Principal Investigator: Marion Subklewe, PD Dr         
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,
  More Information

No publications provided

Responsible Party: PD Dr. Marion Subklewe, Priv. Doz. Dr. med. Marion Subklewe, Ludwig-Maximilians - University of Munich
ClinicalTrials.gov Identifier: NCT01734304     History of Changes
Other Study ID Numbers: 2010-022446-24
Study First Received: October 17, 2012
Last Updated: December 2, 2013
Health Authority: Germany: Paul-Ehrlich-Institut

Keywords provided by Ludwig-Maximilians - University of Munich:
vaccination
postremission therapy
acute myeloid leukemia
dendritic cells

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on November 20, 2014