Therapeutic efficacy of Wilms tumor gene (WT1) mRNA-electroporated autologous dendritic cell vaccination in patients with myeloid malignancies and multiple myeloma:a phase II trial.

• Conditions: Therapeutic vaccination with dendritic cells loaded with wilms' tumor 1 protein in patients with myeloid malignancies and multiple myeloma; MedDRA version: 12.0Level: LLTClassification code 10046859Term: Vaccination; MedDRA version: 12.0Level: LLTClassification code 10024329Term: Leukemia; MedDRA version: 12.0Level: LLTClassification code 10028228Term: Multiple myeloma

• Registration Number: EUCTR2009-015720-28-BE
• Lead Sponsor: Antwerp University Hospital

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-09-21
• Last Update Posted: 7 October 2014

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1. Tumor type:
• Acute Myeloid Leukemia (AML) according to the WHO criteria (ea at least 20% blasts in the marrow). This % should be assessed on a BM aspiration or, in case of dry tap, on a BM biopsy. All FAB subtypes except M3.
(Patients with Myelodysplastic Syndrome, category of Refractory Anemia with Excess Blasts (RAEB): RAEB I (WHO: medullary blast count = 10% and a peripheral blast count = 5%) and RAEB II (WHO: medullary blast count > 10% and/or > 5% peripheral blasts) can be included in the study in absence of other non-experimental treatment modalities.)
• Chronic myeloid leukemia (CML): patients in chronic phase under therapy with tyrosinase kinase inhibitors who have sub-optimal response or failure according to the European Leukemianet guidelines (Baccarani et al. Blood 2006) and who are not eligible for hematopoietic stem cell transplantation
• Multiple Myeloma (MM): symptomatic with active disease:
o Presence of serum/urine M protein (> 3 g/dl)
o Bone marrow plasmacytosis (>10-30%)
o Anemia, renal failure, hypercalcemia, and/or lytic bone lesions

2. Extent of disease:
a. AML:
i. clinical remission after at least one course of polychemotherapy
ii. high risk of relapse defined as (and/or):
1. Age > 60 years (if <60 y, no sibling allotransplant donor available)
2. Poor risk cytogenetic or molecular markers
3. Hyperleukocytosis at presentation
4. Previous relapse
b. CML:
i. Chronic phase and
ii. Not eligible for allogenic stem cell transplantation and
iii. sub-optimal response or failure towards tyrosine kinase inhibitors
iv. or toxicity
c. MM: symptomatic with active disease, independent of earlier and/or
concommitant treatment
3. Overexpression of WT1 RNA in peripheral blood and or bone marrow as assessed by quantitative RT-PCR at the time of presentation.
4. For CML: residual molecular disease as demonstrated by BCR-ABL RT-PCR
5. Prior treatments: Patients must have received at least one prior antileukemic chemotherapeutic regimen and must be more than 1 month past the last treatment.
6. Age: = 18 years
7. Performance status: WHO PS grade 0-1 (Appendix B)
8. Objectively assessable parameters of life expectancy: more than 3 months
9. Prior and concomitant associated diseases allowed with the exception of underlying autoimmune disease and positive serology for HIV/HBV/HCV
10. No concomitant use of immunosuppressive drugs
11. Adequate renal and liver function, i.e. creatinin and bilirubin = 1.2 times the upper limit of normal
12. 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
13. Women of child-bearing potential should use adequate contraception prior to study entry and for the duration of study participation

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Subjects with concurrent additional malignancy (with exception of non-melanoma skin cancers and carcinoma in situ of the cervix)
2. Subjects who are pregnant
3. Subjects who have sensitivity to drugs that provide local anesthesia
4. Subjects needing corticosteroids 1 mg/kg during vaccination; corticosteroids are allowed as part of their treatment when taken = 30 days before the start of vaccination.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified