Clinical trial NCT06429150: Frontline Combination CAR-T Cell Therapy for Multiple Myeloma or Plasmacytoma
Official title: Frontline Management of High-Risk Multiple Myeloma or Plasmacytoma With BCMA and GPRC5D Combination CAR-T Cell Therapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma
Plasmacytoma
Keywords: multiple myeloma
chimeric antigen receptor
BCMA
GPRC5D
Lead sponsor: Shenzhen Geno-Immune Medical Institute
Sponsor class: OTHER
Collaborators: name: The No.2 Clinical Hospital of the Ministry of Health
First posted: 2024-05-24
Enrollment: 20
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 aim of this clinical trial is to assess the feasibility, safety, and efficacy of CAR-T cell therapy targeting multiple cancer cell antigens in high-risk multiple myeloma or plasmacytoma as part of a frontline treatment regimen for patients. Another goal of the study is to learn more about the persistence and function of these CAR-T cells in the body.

Detailed description: Multiple myeloma (MM) is the second most common malignant hematological cancer in the world, which begins with the malignant proliferation of plasma cells in bone marrow. It has been a difficult disease to treat, and most patients will eventually relapse, especially for those with high-risk genotypes. At present, the therapeutic drugs for MM include glucocorticoids, cytotoxic drugs, immunosuppressants, protease inhibitors, monoclonal antibodies and cell therapies. Among those, immunotherapy has been proven to be a revolutionary treatment with great potential of curing this disease. The frequently targeted MM antigens include CD38, CD138, CD19 and BCMA, and recently, GPRC5D.

BCMA, the B cell maturation antigen, also known as CD269 or TNFRSF17, is a member of tumor necrosis factor receptor superfamily, which is highly expressed on the surface of plasma cells and partially expressed on plasma cell-like dendritic cells. It has been an ideal target for MM immunotherapy.

GPRC5D, the G-protein-coupled receptor C57 subtype D and a seven-transmembrane protein, is highly expressed on the surface of plasma cells but not in other healthy cells, and thus it has become a potential target for the treatment of MM. The expression of GPRC5D is unrelated to BCMA, so the combination therapy targeting these antigens may bring a complementary and synergistic therapeutic outcome in patients.

This trial is aimed to test the safety and efficacy of combining these different CAR-T cells targeting BCMA and GPRC5D, and in combination with well-established therapeutics as a frontline treatment for the high-risk MM or plasmacytoma patients. Another goal of this study is to investigate the persistence and function of these CAR-T cells in the body.

Eligibility criteria: Inclusion Criteria:

* Male and female subjects with multiple myeloma or plasmacytoma
* Strictly complete remission (sCR) is a treatment goal
* Expected survival \> 12 weeks
* After prior auto-SCT is eligible regardless of other prior therapies
* Adequate venous access for apheresis, and no other contraindications for leukapheresis
* Voluntary informed consent is given and commitment to continued follow-up

Exclusion Criteria:

* Pregnant or lactating women
* Uncontrolled active infection
* Active HIV, hepatitis B or hepatitis C infection
* Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary.
* Any medical conditions that may preclude participation

Primary outcomes:
measure: Percentage of patients with treatment related adverse effects
timeFrame: 1 month
Secondary outcomes:
measure: Anti-tumor activity of the fourth generation multiple CAR-T cells after infusion
timeFrame: 1 year
measure: Anti-tumor activity of fourth generation multiple CAR-T cells in patients with high-risk MM or plasmacytoma
timeFrame: 1 year
Other outcomes:
Locations:
city: Shenzhen
country: China
facility: Shenzhen Geno-immune Medical Institute
state: Guangdong
city: Vladivostok
country: Russian Federation
facility: Hematologist of the Regional Hematology Center in Clinical Hospital No. 2 of the Ministry of Health
Study officials:
References: