Frontline Combination CAR-T Cell Therapy for Multiple Myeloma or Plasmacytoma

Phase 1

Recruiting

• Conditions: Multiple Myeloma; Plasmacytoma
• Interventions: Biological: CAR-T cells

• Registration Number: NCT06429150
• Lead Sponsor: Shenzhen Geno-Immune Medical Institute

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.

Study Timeline

• Study Start: 2024-05-11
• Study First Submitted: 2024-05-14
• Study First Submitted QC: 2024-05-20
• Study First Posted: 2024-05-24
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-07
• Last Update Posted: 2024-06-10
• Primary Completion: 2027-07-11
• Study Completion: 2027-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 20

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CAR-T cells to treat MM	CAR-T cells	-

Primary Outcome Measures

Name	Time	Method
Percentage of patients with treatment related adverse effects	1 month	The percentage of participants with treatment-related adverse events, as assessed by CTCAE v4.0

Secondary Outcome Measures

Name	Time	Method
Anti-tumor activity of the fourth generation multiple CAR-T cells after infusion	1 year	Anti-tumor activity of the fourth generation multiple CAR-T cells after infusion by measuring the CAR copies in the blood
Anti-tumor activity of fourth generation multiple CAR-T cells in patients with high-risk MM or plasmacytoma	1 year	Anti-tumor activity of fourth generation multiple CAR-T cells in patients with high-risk MM or plasmacytoma by examination of known tumor indicators

Trial Locations

Locations (2)

Shenzhen Geno-immune Medical Institute; 🇨🇳 Shenzhen, Guangdong, China

Hematologist of the Regional Hematology Center in Clinical Hospital No. 2 of the Ministry of Health; 🇷🇺 Vladivostok, Russian Federation