Chronic myeloid leukemia is a malignant disease of the blood. Without therapy it has an unfavourable prognosis. Under first-line therapy with newer inhibitors of the thymidinkinase some few patients only respond poorly. This condition is called "minimal residual disease". The aim of this study is to investigate if a vaccination with autologous dendritic cells can evoke a T-cell response or even improve prognosis in the above mentioned patients.
Conditions
Interventions
Product Name: autologous DC pulsed with peptides + adjuvans
Pharmaceutical Form: Solution for injection
INN or Proposed INN: peptide pulsed DC
Other descriptive name: peptide pulsed DC
Sponsors
Charité Universitätsmedizin Berlin
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients with bcr/abl-positive CML in stable cytogenetic / molekular remission after at least 18 months therapy with tyrosine kinase inhibitors. The following groups of patients will be included: a) complete cytogenetic remission (CCyR), but stable detection of bcr/abl-transkript 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 (70 % 6. Life expectancy > 18 months 7. Hematological function should be at least partially conserved (plts count >50.000/ µl, Hb > 8g/dl) 8. written informed consent 9. No breast feeding 10. if of chilbearing potential, negative pregnancy test (serum/urine ß-HCG) and willingness to use highly effective contraceptive methods (Pearl Index =65 years) yes F.1.3.1 Number of subjects for this age range 15
Exclusion criteria
Exclusion criteria: 1. Clinically relevant autoimmune disorders 2. Immunodeficiency syndromes 3. Known allergy to GM-CSF, TNF-a , IL-4 or KLH 4. Pregnancy (absence confirmed by serum/urine ß-HCG) or breast-feeding 5. Women of childbearing age without highly effective contraception 6. Active infectious disease requiring treatment 7. Continuous therapy with corticosteroids or other immunosuppressive drugs 8. Severe psychiatric disorders 9. Organ dysfunction: a/ Thrombin Time / Partial Thromboplastin Time > 1,5 x upper normal limit b/ creatinine > 2,0 mg/ml c/ Bilirubin > 3,0 mg/ml, ALAT/ASAT > 3x upper normal limit d/ pulmonary disfunction (dyspnea at rest or with minimal exertion) e/ clinically relevant coronary heart disease or ventricular arrhythmia, congestive heart failure > grade II NYHA 10. Persons who are detained officially or legally to an official institute 11. Subjects for whom there is concern about compliance with the protocol procedures 12. 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Feasibility and safety of a long-term vaccination with peptide-pulsed autologous DC in patients with chronic phase CML who have persistent residual cytogenetic and/or molecular disease under at least 18 months therapy with a tyrosine kinase inhibitor.;Secondary Objective: Induction of immunological, cytogenetic and molecular responses;Primary end point(s): Safety and feasibility of a long-term clinical administration of autologous, ex vivo generated peptide-pulsed dendritic cells (DC) in patients with chronic myeloid leukemia. 1) % of grade I/II and grade III/IV toxicities occurring 2) % of patients in whom treatment with the scheduled number of vaccinations and DC is feasible 3) % of patients achieving an improved cytogenetic response 4) % of patients achieving an improved molecular response 5) % of patients in whom leukemia-specific T cells are induced by vaccination 6) Induction of T cell responses in the following subgroups: HLA-A2-, A3- or –B8- and bcr3/abl2– vs. bcr2/abl2- vs. bcr3/abl2 + bcr2/abl2 ;Timepoint(s) of evaluation of this end point: see table 1 of the protocoll (version 1.3, from 27.07.2013), page 10 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Induction of immunological, cytogenetic and molecular responses;Timepoint(s) of evaluation of this end point: see table 1 of the protocoll (version 1.3, from 27.07.2013), page 10 | — |
Countries
Germany
Contacts
Public ContactDr. Jörg Westermann
Charité Universitätsmedizin Berlin
Outcome results
None listed