## Protocol Section
### Identification Module
**NCT ID:** NCT06429150

**Brief Title:** 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

#### Organization Study ID Info
**ID:** GIMI-IRB-24001
#### Organization
**Class:** OTHER
**Full Name:** Shenzhen Geno-Immune Medical Institute
### Status Module
#### Completion Date
**Date:** 2027-12-31

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-24

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-20

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2027-07-11

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-05-11

**Type:** ACTUAL

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-24
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-14
**Study First Submit QC Date:** 2024-05-20
### Sponsor Collaborators Module

#### Collaborators

**Class:** UNKNOWN

**Name:** The No.2 Clinical Hospital of the Ministry of Health

#### Lead Sponsor

**Class:** OTHER

**Name:** Shenzhen Geno-Immune Medical Institute

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**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.

### Conditions Module

**Conditions:**

- Multiple Myeloma

- Plasmacytoma

**Keywords:**

- multiple myeloma

- chimeric antigen receptor

- BCMA

- GPRC5D

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 20

**Type:** ESTIMATED

**Phases:**

- PHASE1

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Intervention Names:**

- Biological: CAR-T cells

**Label:** CAR-T cells to treat MM

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- CAR-T cells to treat MM

**Description:** Infusion of multi-CAR-T cells

**Name:** CAR-T cells

**Type:** BIOLOGICAL

### Outcomes Module

#### Primary Outcomes

**Description:** The percentage of participants with treatment-related adverse events, as assessed by CTCAE v4.0

**Measure:** Percentage of patients with treatment related adverse effects

**Time Frame:** 1 month

#### Secondary Outcomes

**Description:** Anti-tumor activity of the fourth generation multiple CAR-T cells after infusion by measuring the CAR copies in the blood

**Measure:** Anti-tumor activity of the fourth generation multiple CAR-T cells after infusion

**Time Frame:** 1 year

**Description:** Anti-tumor activity of fourth generation multiple CAR-T cells in patients with high-risk MM or plasmacytoma by examination of known tumor indicators

**Measure:** Anti-tumor activity of fourth generation multiple CAR-T cells in patients with high-risk MM or plasmacytoma

**Time Frame:** 1 year

### Eligibility Module

**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

**Maximum Age:** 80 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** c@szgimi.org

**Name:** Lung-Ji Chang, ph.D

**Phone:** 86-0755 86725195

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Shenzhen

**Contacts:**

***Contact 1:***

- **Email:** c@szgimi.com

- **Name:** Lung-Ji Chang, ph.D

- **Phone:** 86-0755-86725195

- **Role:** CONTACT

***Contact 2:***

- **Name:** Vitaly Dubov, MD

- **Role:** PRINCIPAL_INVESTIGATOR

**Country:** China

**Facility:** Shenzhen Geno-immune Medical Institute

**State:** Guangdong

**Status:** RECRUITING

**Zip:** 518000

**Location 2:**

**City:** Vladivostok

**Contacts:**

***Contact 1:***

- **Email:** drvdubov@gmail.com

- **Name:** Vitaly Dubov, MD

- **Phone:** 8(924)3321996

- **Role:** CONTACT

**Country:** Russian Federation

**Facility:** Hematologist of the Regional Hematology Center in Clinical Hospital No. 2 of the Ministry of Health

**Status:** RECRUITING

**Zip:** 690105

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000009370

- Term: Neoplasms by Histologic Type

- ID: D000009369

- Term: Neoplasms

- ID: D000020141

- Term: Hemostatic Disorders

- ID: D000014652

- Term: Vascular Diseases

- ID: D000002318

- Term: Cardiovascular Diseases

- ID: D000010265

- Term: Paraproteinemias

- ID: D000001796

- Term: Blood Protein Disorders

- ID: D000006402

- Term: Hematologic Diseases

- ID: D000006474

- Term: Hemorrhagic Disorders

- ID: D000008232

- Term: Lymphoproliferative Disorders

- ID: D000007160

- Term: Immunoproliferative Disorders

- ID: D000007154

- Term: Immune System Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BC14

- Name: Heart and Blood Diseases

- Abbrev: BC15

- Name: Blood and Lymph Conditions

- Abbrev: BC20

- Name: Immune System Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M12058

- Name: Multiple Myeloma

- Relevance: HIGH

- As Found: Multiple Myeloma

- ID: M27588

- Name: Neoplasms, Plasma Cell

- Relevance: HIGH

- As Found: Multiple Myeloma

- ID: M13844

- Name: Plasmacytoma

- Relevance: HIGH

- As Found: Plasmacytoma

- ID: M12315

- Name: Neoplasms by Histologic Type

- Relevance: LOW

- As Found: Unknown

- ID: M21977

- Name: Hemostatic Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M5059

- Name: Blood Coagulation Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M17400

- Name: Vascular Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M13178

- Name: Paraproteinemias

- Relevance: LOW

- As Found: Unknown

- ID: M5077

- Name: Blood Protein Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M9490

- Name: Hematologic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M9560

- Name: Hemorrhagic Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M11225

- Name: Lymphoproliferative Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M10206

- Name: Immunoproliferative Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M10200

- Name: Immune System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T3947

- Name: Multiple Myeloma

- Relevance: HIGH

- As Found: Multiple Myeloma

- ID: T4587

- Name: Plasmacytoma

- Relevance: HIGH

- As Found: Plasmacytoma

### Condition Browse Module - Meshes

- ID: D000009101

- Term: Multiple Myeloma

- ID: D000054219

- Term: Neoplasms, Plasma Cell

- ID: D000010954

- Term: Plasmacytoma

### Misc Info Module

- Version Holder: 2024-05-31
