DC Vaccination for Postremission Therapy in AML
Primary Purpose
Acute Myeloid Leukemia
Status
Completed
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
DC vaccination for postremission therapy in AML
Sponsored by
About this trial
This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring vaccination, postremission therapy, acute myeloid leukemia, dendritic cells
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
Sites / Locations
- Hospital of the University of Munich, LMU; Department od Medicine III
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
DC vaccination
Arm Description
Vaccination with TLR7/8-matured DCs electroporated with mRNA encoding WT1, PRAME, and CMVpp65
Outcomes
Primary Outcome Measures
% of grade I/II and grade III/IV toxicities
Secondary Outcome Measures
Immune responses to applied antigens
Control of minimal residual disease
Time to progression of disease
ECOG performance status
Full Information
NCT ID
NCT01734304
First Posted
October 17, 2012
Last Updated
October 10, 2018
Sponsor
Ludwig-Maximilians - University of Munich
1. Study Identification
Unique Protocol Identification Number
NCT01734304
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2018
Overall Recruitment Status
Completed
Study Start Date
November 5, 2013 (Actual)
Primary Completion Date
March 31, 2018 (Actual)
Study Completion Date
September 30, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Ludwig-Maximilians - University of Munich
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia
Keywords
vaccination, postremission therapy, acute myeloid leukemia, dendritic cells
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
13 (Actual)
8. Arms, Groups, and Interventions
Arm Title
DC vaccination
Arm Type
Experimental
Arm Description
Vaccination with TLR7/8-matured DCs electroporated with mRNA encoding WT1, PRAME, and CMVpp65
Intervention Type
Biological
Intervention Name(s)
DC vaccination for postremission therapy in AML
Intervention Description
Vaccination with TLR7/8-matured DCs electroporated with mRNA encoding WT1, PRAME, and CMVpp65
Primary Outcome Measure Information:
Title
% of grade I/II and grade III/IV toxicities
Time Frame
30 weeks
Secondary Outcome Measure Information:
Title
Immune responses to applied antigens
Time Frame
30 weeks
Title
Control of minimal residual disease
Time Frame
30 weeks
Title
Time to progression of disease
Time Frame
30 weeks
Title
ECOG performance status
Time Frame
30 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marion Subklewe, PD Dr
Organizational Affiliation
Department of Medicine III; Hospital of the University of Munich,
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital of the University of Munich, LMU; Department od Medicine III
City
Munich
ZIP/Postal Code
81377
Country
Germany
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
32153780
Citation
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.
Results Reference
derived
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DC Vaccination for Postremission Therapy in AML
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