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Malignant (Pleural) MesotheliomaPhase 1PMR-MM-002NCT01241682

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

A Phase 1 study testing DC + CTX in people with Malignant (Pleural) Mesothelioma, run by Erasmus Medical Center at 1 site in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Any age
Conditions the study is for
Malignant (Pleural) Mesothelioma
What is being tested?
DC + CTX
Type of treatment
Vaccines
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
1 siteNetherlands
Study dates
Oct 2009to Oct 2012
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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.
Show all 12Show fewer
  • 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

Who cannot join

  • 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).
Show all 13Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country.

Netherlands1 site

  • Erasmus Medical Center

    Rotterdam, South Holland, 3000 CA

Other trials in Netherlands

About this study

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.

Read the detailed description

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)
Being tested
DC + CTX
Keywords
Mesothelioma, Dendritic cells, Cyclophosphamide, Tumor lysate-loaded, Immunotherapy
Medical subject headings
Mesothelioma, Malignant, Mesothelioma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DC + CTXBiological

    Also called Endoxan

    3x 50x10e6 DC + cyclophosphamide

Study groups in NCT01241682
Study groupRoleWhat they receive
DC immunotherapy + CTXExperimentalPatients 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.
Receives: Biological: DC + CTX

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. number of cytotoxic T cells and regulatory T cells in the blood of patients

    2 weeks before, inbetween (2-weekly, 3 times) and 2 weeks after DC treatment, 7 ml blood samples are collected.

    Measured: up to 1 year

Secondary outcomes (1)

  1. safety and toxicity

    Measured: up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Nov 2010 (estimated)
  2. Study startOct 2009
  3. Primary completionOct 2011
  4. Study completionOct 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01241682
Sponsor's protocol ID
NL24050.000.08
Acronym
PMR-MM-002
Status last verified
Feb 2014
First submitted
1 Jun 2010
Last updated
27 Feb 2014
Results posted
No
Data monitoring committee
Yes

Publications

  • Hegmans JP, Hemmes A, Aerts JG, Hoogsteden HC, Lambrecht BN. Immunotherapy of murine malignant mesothelioma using tumor lysate-pulsed dendritic cells. Am J Respir Crit Care Med. 2005 May 15;171(10):1168-77. doi: 10.1164/rccm.200501-057OC. Epub 2005 Mar 11.

    PubMed 15764728

  • Hegmans JP, Veltman JD, Lambers ME, de Vries IJ, Figdor CG, Hendriks RW, Hoogsteden HC, Lambrecht BN, Aerts JG. Consolidative dendritic cell-based immunotherapy elicits cytotoxicity against malignant mesothelioma. Am J Respir Crit Care Med. 2010 Jun 15;181(12):1383-90. doi: 10.1164/rccm.200909-1465OC. Epub 2010 Feb 18.

    PubMed 20167848

  • Veltman JD, Lambers ME, van Nimwegen M, de Jong S, Hendriks RW, Hoogsteden HC, Aerts JG, Hegmans JP. Low-dose cyclophosphamide synergizes with dendritic cell-based immunotherapy in antitumor activity. J Biomed Biotechnol. 2010;2010:798467. doi: 10.1155/2010/798467. Epub 2010 May 23.

    PubMed 20508851

  • van Gulijk M, Belderbos B, Dumoulin D, Cornelissen R, Bezemer K, Klaase L, Dammeijer F, Aerts J. Combination of PD-1/PD-L1 checkpoint inhibition and dendritic cell therapy in mice models and in patients with mesothelioma. Int J Cancer. 2023 Apr 1;152(7):1438-1443. doi: 10.1002/ijc.34293. Epub 2022 Oct 3.

    PubMed 36104949

  • Cornelissen R, Hegmans JP, Maat AP, Kaijen-Lambers ME, Bezemer K, Hendriks RW, Hoogsteden HC, Aerts JG. Extended Tumor Control after Dendritic Cell Vaccination with Low-Dose Cyclophosphamide as Adjuvant Treatment in Patients with Malignant Pleural Mesothelioma. Am J Respir Crit Care Med. 2016 May 1;193(9):1023-31. doi: 10.1164/rccm.201508-1573OC.

    PubMed 26652184

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing DC + CTX in people with Malignant (Pleural) Mesothelioma, run by Erasmus Medical Center at 1 site in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Feb 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

number of cytotoxic T cells and regulatory T cells in the blood of patients (time frame: up to 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01241682, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Feb 2014.

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