## Protocol Section
### Identification Module
**NCT ID:** NCT06428188

**Acronym:** BAH247

**Brief Title:** Sequential CAR-T Cells Targeting BCMA/CD19 in Patients With Relapsed/ Refractory Autoimmune Diseases

**Official Title:** Sequential CAR-T Cells Targeting BCMA/CD19 in Patients With Relapsed/ Refractory Autoimmune Diseases

#### Organization Study ID Info
**ID:** ESBI202497
#### Organization
**Class:** OTHER
**Full Name:** Essen Biotech
### Status Module
#### Completion Date
**Date:** 2026-12-28

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-31

**Type:** ESTIMATED

**Last Update Submit Date:** 2024-05-29

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2025-12-10

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-05-29

**Type:** ACTUAL

**Status Verified Date:** 2024-05

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

#### Lead Sponsor

**Class:** OTHER

**Name:** Essen Biotech

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** This is an open, single-arm, clinical study to evaluate the efficacy and safety of chimeric antigen receptor T cell immunotherapy (CAR-T) targeting BCMA or CD19 or both sequentially in the treatment of Relapsed/ Refractory Autoimmune Disease such as Sjogren's Syndrome or Systemic Lupus Erythematosus and other Autoimmune Disease.

**Detailed Description:** Chimeric antigen receptor (CAR)-modified T cells targeted against CD19 have demonstrated unprecedented successes in treating patients with hematopoietic and lymphoid malignancies. Besides CD19, many other molecules such as CD22, CD30,BCMA,CD123, etc. may have the potential to develop the corresponding CAR-T cells to treat patients whose tumors express those markers. In this study, investigators will evaluate the safety and efficacy of CAR-T targeting CD19/BCMA in patients with Autoimmune Disease. The primary goal is safety assessment including cytokine storm response and any other adverse effects. In addition, disease status after treatment will also be evaluated.

The purpose of this clinical trial is to assess the feasibility, safety, and efficacy of multiple CAR T-cell therapy that combines CAR T cells against Autoimmune Disease B Cells with CAR T cells targeting BCMA or CD19 or both in patients with relapsed and refractory Autoimmune Disease. The study also aims to learn more about the function of CAR T cells and their persistence in Autoimmune Disease patients.

### Conditions Module

**Conditions:**

- Autoimmune Diseases

- Systemic Lupus Erythematosus

- Systemic Lupus Erythematosus Acute

- Sjogren's Syndrome

**Keywords:**

- Sjogren's Syndrome

- Systemic Lupus Erythematosus

- Autoimmune Diseases

- CAR-T

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

**Intervention Model Description:** Patients enrolled in this clinical trial will receive a carefully designed treatment regimen. Before the infusion of BCMA and CD19 CAR-T cells, participants will undergo preconditioning chemotherapy. This chemotherapy serves to create an optimal environment for CAR-T cell therapy to effectively target and eliminate B cells. Following chemotherapy, participants will receive the infusion of CD19 and BCMA CAR-T cells.

##### Masking Info

**Masking:** NONE

**Masking Description:** Open-label clinical trials are a category of clinical research where the masking is minimal or nonexistent. In such trials, both the participants and the researchers are fully aware of the treatment assignments, which means participants know the treatment they are receiving, and researchers are aware of each participant's treatment group.

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 60

**Type:** ESTIMATED

**Phases:**

- PHASE1

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Patients will be administered fludarabine phosphate intravenously (IV) over a 30-minute period on days -4 to -2. Additionally, cyclophosphamide will be administered intravenously (IV) over 60 minutes on day -2. Subsequently, patients will receive BCMA/CD19 CAR T cells intravenously (IV) over a duration of 10-20 minutes on day 0. Patients who exhibit positive responses to the initial dose of BCMA/CD19 CAR T cells, do not experience unacceptable side effects, and have a sufficient quantity of cells available may be eligible to receive 2 or 3 additional doses of BCMA/CD19 CAR T cells.

**Intervention Names:**

- Biological: BCMA/CD19 CAR-T cells

**Label:** CD19/BCMA-CAR T cells, chemotherapy

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- CD19/BCMA-CAR T cells, chemotherapy

**Description:** The intervention in this clinical trial involves a novel approach using BCMA/CD19 Chimeric Antigen Receptor T (CAR T) cells combined with chemotherapy. The goal is to assess safety and efficacy in patients with specific hematologic malignancies.

Treatment Regimen:

Patients in the trial will undergo the following regimen:

Fludarabine Phosphate (Days -4 to -2): IV administration of fludarabine phosphate over 30 minutes on days -4 to -2. It's part of the preparatory regimen to enhance the body's response to CAR T-cell therapy.

Cyclophosphamide (Day -2): IV cyclophosphamide over 60 minutes on day -2.

BCMA/CD19 Chimeric Antigen Receptor T Cells (Day 0): IV administration of investigational therapy, BCMA/CD19 CAR T cells, over 10-20 minutes on day 0.

Additional Doses: Eligible patients responding well to the initial BCMA/CD19 CAR-T cell infusion without unacceptable side effects and sufficient CAR-T cell availability may receive 2 or 3 additional doses.

**Name:** BCMA/CD19 CAR-T cells

**Type:** BIOLOGICAL

### Outcomes Module

#### Primary Outcomes

**Description:** Will be recorded and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 at three dose levels until the maximum tolerated dose (MTD) is determined.

**Measure:** Incidence and severity of dose-limiting toxicities (DLTs) following chemotherapy preparative regimen and infusion of CD19/BCMA chimeric antigen receptor (CAR) T cells

**Time Frame:** 28 days

#### Secondary Outcomes

**Description:** satisfy the targeted dose level and meet the required release specifications outlined in the Certificate of Analysis (COA)

**Measure:** Rate of successful manufacture and expansion of the CD19/BCMA chimeric antigen receptor (CAR) T cells

**Time Frame:** 60 days

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Expected survival time ≥3 months;
* Subjects with recurrent/refractory autoimmune diseases who have failed standard treatment or lack effective treatment, Including but not limited to systemic lupus erythematosus, idiopathic inflammatory myopathy, systemic sclerosis, IGG4-associated diseases, primary Sjogren's syndrome, rheumatoid arthritis, connective tissue disease-associated interstitial lung disease, immune thrombocytopenia, primary biliary cholangitis, etc.
* Histological evidence of non-suppurative destructive cholangitis and small bile duct destruction.
* Liver and kidney function, cardiopulmonary function meet the following requirements:
* Creatinine ≤1.5×ULN; (2) Electrocardiogram showed no clinically significant abnormal bands;
* Blood oxygen saturation \>91% in non-oxygen state;
* Total bilirubin ≤2×ULN; ALT and AST≤2.5 x ULN; ALT and AST abnormalities due to disease, such as liver infiltration or bile duct obstruction, were determined to be less than 5×ULN. If Gilbert syndrome is diagnosed, the total bilirubin index can be relaxed to ≤3.0×ULN and the direct bilirubin ≤1.5×ULN.
* No serious mental disorders;
* Can understand this test and have signed the informed consent.

Exclusion Criteria:

* Malignant tumors other than R/R AID disease in the 5 years prior to screening, except for adequately treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, local prostate cancer after radical surgery, and breast ductal carcinoma in situ after radical surgery;
* Hepatitis B surface antigen (HBsAg) positive; Hepatitis B core antibody (HBcAb) positive and peripheral blood hepatitis B virus (HBV) DNA titer detection is not within the normal reference value range; Hepatitis C virus (HCV) Antibody positive and peripheral blood hepatitis C virus (HCV) RNA positive; Human immunodeficiency virus (HIV) Antibody positive; Syphilis positive;
* Serious heart disease, including but not limited to unstable angina, myocardial infarction or bypass or stent surgery (within 6 months prior to screening), congestive heart failure (NYHA classification ≥III), and severe arrhythmia;
* Systemic diseases that are deemed unstable by researchers: including but not limited to severe liver, kidney, or metabolic diseases that require drug treatment;
* Active or uncontrollable infections (except mild genitourinary and upper respiratory tract infections) that require systemic treatment within 7 days prior to administration;
* Pregnant or lactating women, and female subjects who plan pregnancy within 2 years after cell transfusion or male subjects whose partners plan pregnancy within 2 years after cell transfusion;
* Patients who received CAR-T therapy or other gene-modified cell therapy before screening;
* Participated in other clinical studies 1 month before screening;
* Evidence of central nervous system invasion during subject screening;
* Mental patients with depression or suicidal thoughts;
* Situations considered unsuitable for inclusion by other researchers.

**Maximum Age:** 90 Years

**Minimum Age:** 21 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** ceo@essen-biotech.com

**Name:** JAMAL ALKHAYER

**Phone:** +97333799773

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Beijing

**Contacts:**

***Contact 1:***

- **Email:** SFM@districtonehospital.com

- **Name:** SAMI XI, dr

- **Phone:** +14012275001

- **Role:** CONTACT

**Country:** China

**Facility:** District One Hospital

**State:** Beijing

**Status:** RECRUITING

**Zip:** 086-373

**Location 2:**

**City:** Shanghai

**Contacts:**

***Contact 1:***

- **Name:** Sami Madsion

- **Role:** CONTACT

***Contact 2:***

- **Email:** SFM@districtonehospital.com

- **Phone:** +97336386689

- **Role:** CONTACT

**Country:** China

**Facility:** District one hospital

**Status:** RECRUITING

### IPD Sharing Statement Module

**IPD Sharing:** UNDECIDED

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000003240

- Term: Connective Tissue Diseases

- ID: D000007154

- Term: Immune System Diseases

- ID: D000001172

- Term: Arthritis, Rheumatoid

- ID: D000001168

- Term: Arthritis

- ID: D000007592

- Term: Joint Diseases

- ID: D000009140

- Term: Musculoskeletal Diseases

- ID: D000012216

- Term: Rheumatic Diseases

- ID: D000014987

- Term: Xerostomia

- ID: D000012466

- Term: Salivary Gland Diseases

- ID: D000009059

- Term: Mouth Diseases

- ID: D000009057

- Term: Stomatognathic Diseases

- ID: D000015352

- Term: Dry Eye Syndromes

- ID: D000007766

- Term: Lacrimal Apparatus Diseases

- ID: D000005128

- Term: Eye Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: BC05

- Name: Musculoskeletal Diseases

- Abbrev: BC07

- Name: Mouth and Tooth Diseases

- Abbrev: BC11

- Name: Eye Diseases

- Abbrev: BC17

- Name: Skin and Connective Tissue Diseases

- Abbrev: BC20

- Name: Immune System Diseases

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M16355

- Name: Syndrome

- Relevance: LOW

- As Found: Unknown

- ID: M15664

- Name: Sjogren's Syndrome

- Relevance: HIGH

- As Found: Sjogren's Syndrome

- ID: M4629

- Name: Autoimmune Diseases

- Relevance: HIGH

- As Found: Autoimmune Diseases

- ID: M11177

- Name: Lupus Erythematosus, Systemic

- Relevance: HIGH

- As Found: Systemic Lupus Erythematosus

- ID: M6464

- Name: Connective Tissue Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M10200

- Name: Immune System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M4476

- Name: Arthritis

- Relevance: LOW

- As Found: Unknown

- ID: M4480

- Name: Arthritis, Rheumatoid

- Relevance: LOW

- As Found: Unknown

- ID: M10621

- Name: Joint Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M12097

- Name: Musculoskeletal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M15045

- Name: Rheumatic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M6323

- Name: Collagen Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M17724

- Name: Xerostomia

- Relevance: LOW

- As Found: Unknown

- ID: M15285

- Name: Salivary Gland Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M12019

- Name: Mouth Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M12017

- Name: Stomatognathic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M18040

- Name: Dry Eye Syndromes

- Relevance: LOW

- As Found: Unknown

- ID: M10664

- Name: Keratoconjunctivitis Sicca

- Relevance: LOW

- As Found: Unknown

- ID: M10786

- Name: Lacrimal Apparatus Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M8271

- Name: Eye Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T170

- Name: Acute Graft Versus Host Disease

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000012859

- Term: Sjogren's Syndrome

- ID: D000008180

- Term: Lupus Erythematosus, Systemic

- ID: D000001327

- Term: Autoimmune Diseases

### Intervention Browse Module - Browse Branches

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: ARhu

- Name: Antirheumatic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M6727

- Name: Cyclophosphamide

- Relevance: LOW

- As Found: Unknown

- ID: M283230

- Name: Fludarabine

- Relevance: LOW

- As Found: Unknown

- ID: M225513

- Name: Fludarabine phosphate

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-31
