DC Vaccination in CML
- Conditions
- Myeloid Leukemia, Chronic
- Interventions
- Biological: DC vaccine
- Registration Number
- NCT02543749
- Lead Sponsor
- Charite University, Berlin, Germany
- Brief Summary
The aim of this phase I/II trial is induction of anti leukemic T cell immunity in a clinical situation of "minimal residual disease". This might be a strategy to immunologically eradicate the residual leukemia cells. Patients to be included are chronic phase bcr/abl+ CML (chronic myeloid leukemia) patients in stable cytogenetic and/or molecular remission.
These patients can be included if they have:
1. not achieved a CMR (complete molecular response) or
2. achieved bcr/abl \< 10% on qPCR (quantitative polymerase chain reaction) (=MCyR) (Major cytogenic Response), but less than a CCyR (complete cytogenic Response).
Autologous DC (Dendritic cells), generated under GMP (Good manufacturing conditions) conditions, are used as a vaccine. These DC constitutively express all putative tumor antigens. In order to ensure sufficient presentation of distinct CML-related antigens, particularly in good responders to TKIs, DC are additionally pulsed with peptides from bcr/abl, WT-1 (Wilms Tumor Protein) and proteinase-3. Monitoring of T cell reactivity against these peptides can then serve as surrogate marker for anti leukemic immunity induced by the vaccine. Vaccination is performed with 10\^7 DC i.d. (intra dermal) in weeks 1, 3, 5, 8, 11, 14, 17, 20, 23 and 26. KLH (keyhole limpet hemocyanin) is used as an adjuvant for vaccine preparations in weeks 3, 5 and 8 (and 11).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 1
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Patients with bcr/abl-positive CML in stable cytogenetic / molecular remission after at least 18 months therapy with tyrosine kinase Inhibitors (TKI). The following groups of patients will be included:
- complete cytogenetic remission (CCyR), but stable detection of bcr/abl-transcript on qPCR (at least on two different time points over a period of at least 6 months). A stable molecular remission is assumed, if the difference between the qPCR values does not exceed a factor 5 (< 0,5log).
- No CCyR, but qPCR for bcr/abl transcript < 10% (= MCyR (Major cytogenetic Response)) after at least 24 months on 2nd generation TKI therapy.
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Treatment with a TKI inhibitor and an additional anti leukemic drug is no exclusion criterion.
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Age 18-80 years
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Performance status of 0 or 1 according to WHO index or Karnofsky index >70 %
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Life expectancy > 18 months
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Hematological function should be at least partially conserved (platelets count >50.000/ μl, Hb > 8g/dl)
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written informed consent
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No breast feeding
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if of childbearing potential, negative pregnancy test (serum/urine ß- HCG ( human chorionic gonadotropin )) and willingness to use highly effective contraceptive methods (Pearl Index <1, e.g.: birth control pill, loop, hormone implant, transdermal hormone patch, a combination of two barrier methods [condom and vaginal diaphragm] sterilisation or sexual abstinence) for the study duration and thereafter as long as under treatment with antileukemic drugs
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Clinically relevant autoimmune disorders
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Immunodeficiency syndromes
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Known allergy to GM-CSF (granulocyte macrophage colony-stimulating factor), TNF-α (Tumor necrosis factor Alpha) , IL-4 (interleukine 4) or KLH (keyhole limpet hemocyanin)
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Pregnancy (absence confirmed by serum/urine ß-HCG) or breastfeeding
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Women of childbearing age without highly effective contraception
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Active infectious disease requiring treatment
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Continuous therapy with corticosteroids or other immunosuppressive drugs
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Severe psychiatric disorders
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Organ dysfunction:
- Thrombin Time / Partial Thromboplastin Time > 1,5 x upper normal limit
- creatinine > 2,0 mg/ml
- Bilirubin > 3,0 mg/ml, ALAT/ASAT (Alanine aminotransferase/ aspartate aminotransferase) > 3x upper normal limit
- pulmonary disfunction (dyspnea at rest or with minimal exertion)
- clinically relevant coronary heart disease or ventricular arrhythmia, congestive heart failure > grade II NYHA (New York Heart Association)
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Persons who are detained officially or legally to an official institute
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Subjects for whom there is concern about compliance with the protocol procedures
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Present History of substance abuse (drug or alcohol) or any other factor (e.g., serious psychiatric condition) that could limit the subject's ability to comply with study procedures
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description DC vaccine DC vaccine Autologous DC pulsed with leukemia-associated peptides+adjuvant. Ten vaccinations over 26 weeks with 10 x 106 freshly thawed DC Intradermal injections (1-2 ml volume)
- Primary Outcome Measures
Name Time Method DC toxicity Parameters using CTC (Common toxicity criteria) 30 weeks Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0 (Treatment: long-term vaccination with peptide-pulsed autologous DC in patients with chronic phase CML who have persistent residual cytogenetic and/or molecular disease after at least 18 months therapy with a tyrosine kinase Inhibitor)
- Secondary Outcome Measures
Name Time Method T-cell Response: Antigen specific T-cell Response in % CD8+ T-cells for bcr/abl 30 weeks T-cell Response: Antigen specific T-cell Response in % CD4+ T-cells for bcr/abl 30 weeks T-cell Response: Antigen specific T-cell Response in % CD8+ T-cells for Proteinase 3 (only in HLA-A2+ patients) 30 weeks Molecular/cytogenetic Response under vaccination as measured by qPCR for bcr/abl in % IS (International scale) 30 weeks T-cell Response: Antigen specific T-cell Response in % CD8+ T-cells for WT-1 (only in HLA-A2+ patients) 30 weeks
Trial Locations
- Locations (2)
Charité - University Medicine Berlin
🇩🇪Berlin, Germany
Klinikum Bremen Mitte
🇩🇪Bremen, Germany