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Dendritic cell therapy is a promising strategy for adjuvant cancer therapy in the setting of minimal residual disease (MRD) to fight off cancer relapse and/or progression. The investigators already performed a phase I safety study in leukemia patients that were in complete remission demonstrating the absence of side effects and feasibility of the therapy. Here, the investigators want to extend on this strategy by studying the clinical efficacy of autologous DC vaccination in patients with acute and chronic myeloid leukemia and myeloma patients. Effects of DC therapy on the immune reactivity towards leukemia cells as well as clinical parameters such molecular MRD monitoring, time to relapse (TTR), progression-free survival (PFS) and overall survival(OS) will be studied in vaccinated and non-vaccinated (control) patients. Patients will be vaccinated using their own dendritic cells electroporated with mRNA coding for the full-length Wilms' tumor antigen WT1.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| standard therapy + vaccination | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| dendritic cell vaccination (active specific immunotherapy) | Biological |
|
| Measure | Description | Time Frame |
|---|---|---|
| Immunogenicity of WT1 mRNA-transfected DC vaccination | Upon completion of blood sample collection (before start of the vaccination at week 0 and 8 weeks after start of the vaccination) and skin biopsy collection (8 weeks after start of the vaccination) for all included patients | |
| Induction/maintenance of molecular remission as evidenced by molecular MRD monitoring of WT1 (AML, CML and MM) and BCR/ABL RNA (CML) copies in peripheral blood | Upon follow-up completion for all included patients, i.e. until 24 months after the last vaccination |
| Measure | Description | Time Frame |
|---|---|---|
| Time to relapse (TTR) | Upon follow-up completion for all included patients, i.e. until 24 months after the last vaccination | |
| progression-free survival | Upon follow-up completion for all included patients, i.e. until 24 months after the last vaccination |
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Inclusion Criteria:
Acute Myeloid Leukemia (AML): all FAB subtypes except M3. Extent of disease:
Chronic myeloid leukemia (CML): patients in chronic phase under therapy with tyrosinase kinase inhibitors who have sub-optimal response or failure and who are not eligible for hematopoietic stem cell transplantation.
Multiple Myeloma (MM): symptomatic with active disease, independent of earlier and/or concomitant treatment:
Overexpression of WT1 RNA in peripheral blood and or bone marrow as assessed by quantitative RT-PCR at the time of presentation.For CML: residual molecular disease as demonstrated by BCR-ABL RT-PCR
Prior treatments: Patients must have received at least one prior antileukemic chemotherapeutic regimen and must be more than 1 month past the last treatment.
Age: ≥ 18 years
Performance status: WHO PS grade 0-1 (Appendix B)
Objectively assessable parameters of life expectancy: more than 3 months
Prior and concomitant associated diseases allowed with the exception of underlying autoimmune disease and positive serology for HIV/HBV/HCV
No concomitant use of immunosuppressive drugs
adequate renal and liver function, i.e. creatinin and bilirubin = 1.2 times the upper limit of normal
absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
Women of child-bearing potential should use adequate contraception prior to study entry and for the duration of study participation
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospital Antwerp | Edegem | Antwerp | 2650 | Belgium |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 19530029 | Background | Van Driessche A, Van de Velde AL, Nijs G, Braeckman T, Stein B, De Vries JM, Berneman ZN, Van Tendeloo VF. Clinical-grade manufacturing of autologous mature mRNA-electroporated dendritic cells and safety testing in acute myeloid leukemia patients in a phase I dose-escalation clinical trial. Cytotherapy. 2009;11(5):653-68. doi: 10.1080/14653240902960411. | |
| 19289488 |
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| ID | Term |
|---|---|
| D015470 | Leukemia, Myeloid, Acute |
| D015464 | Leukemia, Myelogenous, Chronic, BCR-ABL Positive |
| D009101 | Multiple Myeloma |
| ID | Term |
|---|---|
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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| overall survival (OS) | Upon follow-up completion for all included patients, i.e. until 24 months after the last vaccination |
| Smits EL, Berneman ZN, Van Tendeloo VF. Immunotherapy of acute myeloid leukemia: current approaches. Oncologist. 2009 Mar;14(3):240-52. doi: 10.1634/theoncologist.2008-0165. Epub 2009 Mar 16. |
| 16121214 | Background | Van Driessche A, Gao L, Stauss HJ, Ponsaerts P, Van Bockstaele DR, Berneman ZN, Van Tendeloo VF. Antigen-specific cellular immunotherapy of leukemia. Leukemia. 2005 Nov;19(11):1863-71. doi: 10.1038/sj.leu.2403930. |
| 19656053 | Background | Smits EL, Anguille S, Cools N, Berneman ZN, Van Tendeloo VF. Dendritic cell-based cancer gene therapy. Hum Gene Ther. 2009 Oct;20(10):1106-18. doi: 10.1089/hum.2009.145. |
| 28830889 | Derived | Anguille S, Van de Velde AL, Smits EL, Van Tendeloo VF, Juliusson G, Cools N, Nijs G, Stein B, Lion E, Van Driessche A, Vandenbosch I, Verlinden A, Gadisseur AP, Schroyens WA, Muylle L, Vermeulen K, Maes MB, Deiteren K, Malfait R, Gostick E, Lammens M, Couttenye MM, Jorens P, Goossens H, Price DA, Ladell K, Oka Y, Fujiki F, Oji Y, Sugiyama H, Berneman ZN. Dendritic cell vaccination as postremission treatment to prevent or delay relapse in acute myeloid leukemia. Blood. 2017 Oct 12;130(15):1713-1721. doi: 10.1182/blood-2017-04-780155. Epub 2017 Aug 22. |
| D006402 |
| Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D009196 | Myeloproliferative Disorders |
| D001855 | Bone Marrow Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D054219 | Neoplasms, Plasma Cell |
| D020141 | Hemostatic Disorders |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006474 | Hemorrhagic Disorders |
| D008232 | Lymphoproliferative Disorders |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |