Dendritic Cell-based Immunotherapy Combined With Low-dose Cyclophosphamide in Patients With Malignant Mesothelioma

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

10 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-10-31

Study Completion Date

2012-10-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

Earlier the investigators determined the safety and feasibility of tumor lysate-pulsed dendritic cells as therapeutic adjuvants in mesothelioma patients. Because pre-clinical data in mice had shown that better results were obtained when regulatory T cells were depleted using low-dosis of cyclophosphamide, ten patients who responded on chemotherapy are selected for DC-treatment in combination with Endoxan.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Dendritic Cell-based Immunotherapy in Mesothelioma

NCT00280982

Malignant Pleural Mesothelioma

COMPLETED PHASE1

Dendritic Cells Loaded With Allogeneous Cell Lysate in Mesothelioma Patients

NCT02395679

Mesothelioma

UNKNOWN PHASE1

Autologous Dendritic Cell Vaccination in Mesothelioma

NCT02649829

Malignant Pleural Mesothelioma

COMPLETED PHASE1/PHASE2

Dendritic Cell Vaccination for Patients with Solid Tumors

NCT01291420

Glioblastoma Renal Cell Carcinoma Sarcomas +3 more

COMPLETED PHASE1/PHASE2

Dendritic Cell Based Therapy of Malignant Melanoma

NCT00197912

Advanced Melanoma

COMPLETED PHASE1/PHASE2

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Currently there is no satisfactory low-toxicity treatment for patients with mesothelioma (MM). Based on studies in other types of cancer in humans where beneficial effects were obtained, and based on our pre-clinical data in a mouse model for MM, led to the introduction of DC-immunotherapy for human MM in 2005. A beneficial effect of immunotherapy in MM patients without major side effects was found, however, research has shown that DC immunotherapy might be further improved. The objectives of the here proposed phase study are:

* To define the safety and toxicity of low dose CTX in combination with MesoCancerVac in patients with MM.
* To determine if vaccination with low dose CTX in combination with MesoCancerVac results in a detectable immune response by skin DTH reactions on MM crude antigen and KLH and by in vitro laboratory analysis.
* To observe and document anti-cancer activity by laboratory evaluation (e.g. decrease in Tregs, increase in CTLs using 51Cr release and IFN-gamma ELISPOT)
* To observe and document anti-cancer activity by clinical evaluation (e.g. CT scan)

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Malignant (Pleural) Mesothelioma

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

DC immunotherapy + CTX

Patients with mesothelioma who are fit enough to be treated with chemotherapy and enough tumor material was available are asked for participation in this study. After 4 cycles of Alimta chemotherapy, a leukapheresis is performed of which the monocytes are used for differentiation to DCs using different cytokines. The procedure to grow DCs in vitro and pulse them with tumor lysate is performed according to our earlier performed phase I study that was approved by our local ethics committee. Three doses of properly pulsed autologous DCs (MesoCancerVac) are then re-injected every two weeks. Patients will be treated with a low dose of CTX for seven day in a row the week before the 1st vaccination, the weeks in between the 2nd, and for one week after the 3rd vaccination.

Group Type EXPERIMENTAL

DC + CTX

Intervention Type BIOLOGICAL

3x 50x10e6 DC + cyclophosphamide

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

DC + CTX

3x 50x10e6 DC + cyclophosphamide

Intervention Type BIOLOGICAL

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Endoxan

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Patients with clinically and histological or cytological confirmed newly diagnosed MM, that can be measured in two dimensions by a radiologic imaging study.
* Patients must be at least 18 years old and must be able to give written informed consent.
* Patients must be ambulatory (Karnofsky scale \> 70, or WHO-ECOG performance status 0,1, or 2) and in stable medical condition. The expected survival must be at least 4 months.
* Patients must have normal organ function and adequate bone marrow reserve: absolute neutrophil count \> 1.5 x 109/l, platelet count \> 100 x 109/l, and Hb \> 6.0 mmol/l.
* Positive DTH skin test (induration \> 2mm after 48 hrs) against at least one positive control antigen tetanus toxoid.
* Stable disease or response after chemotherapy.
* Availability of sufficient tumor material of the patient.
* Ability to return to the Erasmus MC for adequate follow-up as required by this protocol.
* Able to tolerate oral therapy
* No impairment of gastrointestinal (GI) function or GI disease that may affect or alter absorption of CTX (e.g., mal-absorption syndrome, history of total gastrectomy/significant small bowel resection)
* No history of allergic reactions (≥ grade 3 or 4) to compounds of similar chemical or biologic composition to CTX (i.e., alkylating agents)
* No known intolerance or hypersensitivity reaction to CTX

Exclusion Criteria

* Conditions that make the patient unfit for chemotherapy or progressive disease after 4 cycles of chemotherapy.
* Pleurodesis at the affected side before the pleural fluid is obtained.
* Medical or psychological impediment to probable compliance with the protocol.
* Patients on steroid (or other immunosuppressive agents) are excluded on the basis of potential immune suppression. Patients must have had 6 weeks of discontinuation and must stop of any such treatment during the time of the study.
* No prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, superficial or in-situ cancer of the bladder or other cancer for which the patient has been disease-free for five years.
* Serious concomitant disease, no active infections. Patients with a history of autoimmune disease or organ allografts, or with active acute or chronic infection, including HIV (as determined by ELISA and confirmed by Western Blot) and viral hepatitis (as determined by HBsAg and Hepatitis C serology).
* Patients with serious intercurrent chronic or acute illness such as pulmonary (asthma or COPD) or cardiac (NYHA class III or IV) or hepatic disease or other illness considered by the study coordinator to constitute an unwarranted high risk for investigational DC treatment.
* Patients with a known allergy to shell fish (may contain KLH).
* Pregnant or lactating women.
* Patients with inadequate peripheral vein access to perform leukapheresis
* Concomitant participation in another clinical trial
* An organic brain syndrome or other significant psychiatric abnormality which would comprise the ability to give informed consent, and preclude participation in the full protocol and follow-up.
* Absence of assurance of compliance with the protocol. Lack of availability for follow-up assessment.

Eligible Sex

ALL

Accepts Healthy Volunteers

No