Clinical trial NCT06435910: Engineered Dendritic Cell Vaccines for Multiple Myeloma
Official title: Engineered Dendritic Cell Vaccines for Remission Maintenance in Multiple Myeloma Patients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Multiple Myeloma or Plasmacytoma
Keywords: MM
CAR T
DC vaccine
Lead sponsor: Shenzhen Geno-Immune Medical Institute
Sponsor class: OTHER
Collaborators: name: The No.2 Clinical Hospital of the Ministry of Health
First posted: 2024-05-30
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the feasibility, safety, and efficacy of dendritic cell (DC) vaccines in the treatment of multiple myeloma (MM) or plasmacytoma based on immune-modified DC vaccines (DCvac). This approach is aimed to achieve prolonged maintenance of remission in multiple myeloma or plasmacytoma patients.

Detailed description: Multiple myeloma (MM) is a plasma cell malignancy, characterized by the aberrant occupation of bone marrow with malignant plasma cells, and the destruction of bones together with the production of abnormal immunoglobulins. The clinical symptoms and signs can be manifested through various mechanisms. At present, the therapeutic drugs for MM include glucocorticoid, cytotoxic drugs, immunosuppressants, protease inhibitors, monoclonal antibodies and cell therapies including hematopoietic stem cell transplantation (HSCT). Among them, immunotherapy has been proven to be a revolutionary treatment with great potential of producing long term cure.

In the past decades, adoptively transferred T cells modified with chimeric antigen receptors (CARs) have demonstrated high effectiveness, and the CAR-T therapy has changed the treatment paradigm for many hematological malignancies. Currently, several antibody-based therapies and a few BCMA-based CAR-T cell therapies have been approved for MM treatment. However, in many MM patients, the disease may still relapse after extensive immunotherapies including auto- and allo-HSCT. We have previously reported a DC-based immune activation strategy against MM in a preclinical study. This study proposes to apply the individual patients' MM tumor antigen-based DCs as vaccines (DCvac) to booster anti-myeloma immunity, in order to prevent disease relapse. The MM patients who have achieved very good partial or complete remission will be treated with multiple DCvacs to achieve a prolonged remission without disease recurrence.

This trial protocol will inject DCvacs to MM or plasmacytoma patients who have been treated with a combination of anti-cancer regimens, including CAR-T cell therapy, and who have achieved partial or complete disease remission. The DCvacs are patient's own DCs which are immune modified to present target antigens and to activate anti-cancer immunity. The aim of this study is to evaluate the feasibility, safety, and efficacy of the innovative MM patient-based DC vaccines.

Eligibility criteria: Inclusion Criteria:

* Male and female subjects with multiple myeloma or plasmacytoma
* Very good partial or complete remission (CR) after prior combination therapies.
* Expected survival \> 12 weeks
* Adequate venous access for blood withdrawal or apheresis, and no other contraindications for blood withdrawal
* Voluntary informed consent is given with willingness to continue follow up

Exclusion Criteria:

* Pregnant or lactating women
* Uncontrolled active infection
* HIV or active hepatitis B or hepatitis C infection
* Concurrent use of systemic steroids; the use of inhaled steroids is not exclusionary

Primary outcomes:
measure: Safety of DC injection
timeFrame: 1 Month
Secondary outcomes:
measure: Clinical response
timeFrame: 1 year
Other outcomes:
Locations:
city: Shenzhen
country: China
facility: Shenzhen Geno-immune Medical Institute
state: Guangdong
city: Vladivostok
country: Russian Federation
facility: The Regional Hematology Center in Clinical Hospital No. 2 of the Ministry of Health
Study officials:
References:
citation: Han S, Wang B, Cotter MJ, Yang LJ, Zucali J, Moreb JS, Chang LJ. Overcoming immune tolerance against multiple myeloma with lentiviral calnexin-engineered dendritic cells. Mol Ther. 2008 Feb;16(2):269-79. doi: 10.1038/sj.mt.6300369. Epub 2007 Dec 11.
citation: Ayed AO, Chang LJ, Moreb JS. Immunotherapy for multiple myeloma: Current status and future directions. Crit Rev Oncol Hematol. 2015 Dec;96(3):399-412. doi: 10.1016/j.critrevonc.2015.06.006. Epub 2015 Jun 28.