The primary goal is to show the capability of monocyte-derived DC after RNA electroporation for multiple antigens to induce an immune response. The secondary objective is to show clinical response.
ID
Source
Brief title
Condition
- Plasma cell neoplasms
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
In vivo immune response to the tumor associated antigen epitopes in at least 3
out of 10 patients will be considered as a positive result. No response to any
of the antigens will be considered a negative result.
Secondary outcome
Secondary end-points are clinical responses a decrease of minimal residual
disease by molecular monitoring (ASO-PCR).
Background summary
Patients with multiple myeloma (MM) are treated with intensive chemotherapy,
which frequently induces a status of minimal residual disease, but finally all
patients will relapse. Allogeneic transplantation as a form of immunotherapy
may prolong remission and even cures the disease, but only in a minority of the
patients and with significant toxicity. In a pilot study we vaccinated MM
patients with mature DC loaded with idiotype as an alternative form of
immunotherapy. We showed the feasibility and a very limited toxicity, but the
idiotype antigen appeared only weakly immunogenic. In this study we will
vaccinate with 3 different proteins, Mage-3, Survivin and BCMA, all shown to be
highly expressed on malignant plasma cells. Autologous RNA electroporated
mature DC will be used to present the antigens to the immune system.
Study objective
The primary goal is to show the capability of monocyte-derived DC after RNA
electroporation for multiple antigens to induce an immune response. The
secondary objective is to show clinical response.
Study design
This is an observational study in a series of 10 patients. Patients will be
treated by 3 DC vaccinations at 2 weeks interval. In case of response the
procedure can be repeated to boost the immune response.
Intervention
Patients monocytes will collected by apheresis. Patients will be vaccinated
intravenous and intradermal at 3 occasions with 2 weeks interval. Monitoring
will be done for toxicity, immune response and minimal residual disease.
Study burden and risks
In a pilot study and studies with DC vaccination in other malignancies (> 80
patients treated) the toxicity was limited to local reactions at the site of
injection, allergic reactions, fever or chills. Apheresis is a safe procedure,
already performed before in these patients to collect stem cells for autologous
transplantation. For follow-up we will collect blood (at day 14, 28, 39 and 56
after DC vaccination) and bone marrow aspirates (at 3, 6, 12 months after
chemotherapy during 1st year).
Geert Grooteplein zuid 10
6525 GA
NL
Geert Grooteplein zuid 10
6525 GA
NL
Listed location countries
Age
Inclusion criteria
· Age 18-70 years
· Patients with stage II and III MM
· Complete remission (CR) or partial response (PR) following intensive therapy, including high dose melphalan and autologous stem cell transplantation
· Measurable minimal residual disease by M-component (complete of light chain) or molecular disease by BM ig heavy chain rearrangement (ASO-PCR)
·Myeloma cells expressing 2-3 of the 3 TAA used for vaccination, each in >20% of CD138+CD38++ plasma cells
· Interval of >6 months after completion of intensive chemotherapy.
· Life expectancy >6 months
· Expected adequacy for follow-up including bone marrow evaluation
· Written Informed consent
Exclusion criteria
· Progressive disease (increase in M-component of >25% in the last 3 months)
· Patients on immunosuppressive drugs
· Patients with active infections (viral, bacterial or fungal) that requires specific therapy. Acute therapy must have been completed within 14 days prior to study treatment.
· Patients with known allergy to shell fish (contains KLH).
· Patients with pregnancy or lactation
· WHO performance status 4
· Allogeneic stem cell transplantation
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2006-003492-12-NL |
| CCMO | NL13547.000.06 |