BCMA-CD19 CCAR T Cell Treatment of Refractory Immune Thrombocytopenia Associated with Autoimmune Diseases

Treatment of Refractory Immune Thrombocytopenia

This is a phase I, interventional, single arm, open label, treatment study to evaluate the safety and tolerability of BCMA-CD19 cCAR T cells in patients with refractory ITP associated with autoimmune disease.

Study Overview

• Status: Recruiting
• Conditions: Refractory Immune Cytopenia
• Intervention / Treatment: Biological: BCMA-CD19 cCAR T cells

Detailed Description

Immune thrombocytopenia (ITP) Can be associated with various autoimmune diseases, including SLE, and SS. Patients with refractory thrombocytopenia often have long hospital stays, high medical costs, high demand for blood products, and are prone to complications of other systemic injuries. Such patients require active treatment to reduce the risk of life-threatening bleeding, delay the progression of the disease prognosis Glucocorticoids combined with immunosuppressive agents are still the main treatment strategies. Recently, biological agents targeting abnormal immune cells, such as rituximab and belimumab, which deplete B cells have also achieved some success in the treatment of ITP. However, these agents cannot permanently reverse the production of abnormal antibodies as they are unable to eliminate pathogenic long-lived plasma cells because these agents cannot penetrate lymph nodes and soft tissue. The BCMA-CD19 cCAR T-cells are designed to deplete antibody-producing 'root", B cells and plasma cells.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Qibing Xie, MD; Phone Number: 0118618980601299; Email: xieqibing1971@163.com
• Study Contact Backup: Name: Min Yang, MD; Phone Number: 13618028207; Email: yangmin7911@126.com

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Recruiting
      • West China Hospital
      • Contact: Min Yang, MD; Phone Number: 13618028207; Email: yangmin7911@126.com
      • Contact: Qibing Xie, MD; Phone Number: 011-86-18980601299; Email: xieqibing1971@163.com
      • Contact: Qibing Xie, MD
      • Contact: Min Yang, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1. Age: 18~60 years old; 2. Diagnosed with immune thrombocytopenia associated with autoimmune diseases including systemic lupus erythematosus (according to the 1997 or 2009 ACR classification criteria), primary Sjogren's syndrome (according to the 2002 ACR/EULAR international classification criteria), undifferentiated connective tissue disease (according to the 1999 international classification criteria). Or patient without clinical manifestations related to connective tissue disease, but with positive anti nuclear antibodies (≥ 1:100) and/or without positive anti SSA/Ro-52 antibodies;Serum creatinine <221.0μmol/L (2.5mg/dl); 3. platelet count<30 × 10 ⁹/L or platelet count ≥ 20 × 10 ⁹/L, accompanied by bleeding symptoms (bleeding symptom score ≥ 2 points). No obvious active infection; 4. Voluntary participation and informed consent signed by the patient or his/her legal/authorized representative.

Exclusion Criteria:

- 1. Serious accompanying diseases that researchers consider clinically significant due to poor control, such as (but not limited to) neurological, cardiovascular, renal, liver, endocrine, or gastrointestinal diseases CNS disease: Active central nervous system (CNS) lupus (including epilepsy, psychosis, organic encephalopathy syndrome, cerebrovascular accident [CVA], encephalitis or CNS vasculitis), visual Disorders, cranial neuropathy requiring intervention 2. Abnormal liver function: aspartate transaminase (AST) or alanine transaminase (ALT) or glutamyl transpeptidase (GGT) detection value is greater than 1.5 times the upper limit of normal (ULN);; urinary protein quantification>1g/24h.

3. History of malignant tumors 4. Active hepatitis B or C.，and HIV positive 5. Individuals with a history of drug allergies or allergies. 6. Have any other clinically significant disease history or current disease that, in the judgment of the research physician, may pose a risk to the safety of the subjects, or interfere with the completion of the research procedure and the evaluation of safety and efficacy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BCMA-CD19 cCAR T cells; Dose escalation phase: patient's T cells will be transduced with a retroviral vector to express a BCMA-CD19 cCAR. with an escalation approach.	Biological: BCMA-CD19 cCAR T cells; • BCMA-CD19 cCAR T cells are used to treat patients. Patient will be administered either fresh or thawed CAR T cells by IV injection after receiving lymphodepleting chemotherapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The number and incidence of adverse events after BCMA-CD19 cCAR T cell infusion	Evaluation all possible adverse reactions, including the number, incidence, and severity of symptoms such as cytokine release syndromes and neurotoxicity within 3 months after BCMA-CD19 cCAR infusion.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall remission rate 12 weeks after BCMA-CD19 cCAR	Complete response (CR): Platelet count ≥ 100 × 109/L and no bleeding;; Partial response (PR): platelet count<100 × 109/L, but increased by at least 2 times compared to baseline platelet count, with no bleeding symptoms; Disease control: Disease control monitored up to 2 years after BCMA-CD19 cCAR T cells infusion)	24 months

Collaborators and Investigators

• Sponsor: iCell Gene Therapeutics
• Collaborators: iCell ImmunityX（Hangzhou）Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): August 31, 2024
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: January 8, 2025
• First Submitted That Met QC Criteria: January 16, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 16, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: CAR T cells; immune thrombocytopenia; BCMA-CD19 cCAR; autoimmune diseaases
• Additional Relevant MeSH Terms: Pathologic Processes; Autoimmune Diseases; Immune System Diseases; Hemorrhage; Skin Manifestations; Hematologic Diseases; Blood Coagulation Disorders; Hemorrhagic Disorders; Blood Platelet Disorders; Thrombotic Microangiopathies; Purpura, Thrombocytopenic; Purpura; Cytopenia; Thrombocytopenia; Purpura, Thrombocytopenic, Idiopathic
• Other Study ID Numbers: ICG318-ITP-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No