Fourth-gen CAR T Cells Targeting BCMA/CD19 for Refractory Systemic Lupus Erythematosus (SLE) (BAH242)

October 11, 2024 updated by: Essen Biotech

T-cell Infusion Targeting BCMA and CD19 for Refractory/Relapsed Systemic Lupus Erythematosus (SLE) Patients With or Without Organs Involvement

This study is a preliminary investigation, with a single-group design, not randomized and transparent, focusing on treatment. Its purpose is to identify the highest dose of BH002 injection (CD19-BCMA CAR-T cells) that patients suffering from resistant systemic lupus erythematosus can tolerate.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Systemic lupus erythematosus (SLE) is a type of autoimmune disorder characterized by the creation of autoantibody-generating immune complexes, affecting various systems and organs.

In SLE, autoreactive B cells can self-activate and morph into plasma cells that produce a high volume of autoantibodies. These cells can also expose their own antigens to autoimmune T cells, thereby stimulating T cells and leading to the release of inflammatory substances.

Conventional treatment for SLE focuses on achieving prolonged remission. In contrast, CD19-BCMA CAR-T cells offer a potential solution by eradicating the abnormal B cells responsible for antibody production. This allows for the rebuilding of the immune system and the restoration of normal immune function in patients, potentially leading to a life free from medication. This highlights the promising potential of CAR-T therapy in treating SLE.

Study Type

Interventional

Enrollment (Estimated)

75

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 086-373

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 18-90 years old;
  • Total score ≥ 10 on the EULAR/ACR 2019 SLE classification criteria.
  • SELENA-SLEDAI≥8.
  • Patients with CD19+ B-cell.
  • Hemoglobin≥85 g/L.
  • WBC≥2.5×10^9/L.
  • NEUT≥1×10^9/L.
  • BPC≥50×10^9/L.
  • AST/ALT below 2 times the upper limit of normal; Creatinine clearance ≥30 mL/min; blood bilirubin ≤2.0 mg/dl; echocardiography indicates that the ejection fraction is ≥50%.
  • Adequate venous access for apheresis, and no other contraindications for leukapheresis.
  • Women of childbearing age should have a negative serum or urine pregnancy test at screening and baseline.
  • Subjects agree to take effective contraceptive measures during the trial until at least 1 year after CAR-T cells infusion.
  • Agree to attend follow-up visits as required.
  • Voluntary participation and informed consent signed by the patient or his/her legal/authorized representative.

Exclusion Criteria:

  • Renal disease: severe lupus nephritis (serum creatinine > 2.5 mg/dL or 221 μmol/L) within 8 weeks --Prior to leukapheresis, or subjects who need hemodialysis.
  • CNS disease: including epilepsy, psychosis, organic encephalopathy syndrome, cerebrovascular accident [CVA], encephalitis or CNS vasculitis, psychiatric patients with depression or suicidal thoughts.
  • Patients with serious lesions and a history of present illness of vital organs such as the heart, liver,kidney blood and endocrine system.
  • Patients with immunodeficiency, uncontrolled active infections and active or recurrent peptic ulcers;
  • Received immunosuppressive therapy within 1 week prior to leukapheresis.
  • Patients with HIV infection; Active infection of hepatitis B virus or hepatitis C virus.
  • Patients with syphilis infection.
  • The presence or suspicion of an active fungal, bacterial, viral or other infection that cannot be controlled during screening.
  • Received live vaccine treatment within 4 weeks prior to screening.
  • Severe allergies or hypersensitivity.
  • Contraindication to cyclophosphamide in combination with fludarabine.
  • Subjects who have undergone major surgery within 2 weeks prior to signing the informed consent form, or who are scheduled to have surgery (other than local anesthetic surgery) during the trial or within 2 weeks of the infusion.
  • Cannula or drainage tubes other than central venous catheters.
  • Pregnant or lactating women, or subjects who plan to have children within 1 year of treatment;
  • Subjects with prior CD19 or BCMA-targeted therapy.
  • Participated in any clinical study within 3 months prior to enrollment.
  • Subjects with malignant tumour, except for Non-melanoma Skin Cancer with PFS>5yr; Cervical Cancer in situ; Bladder Cancer; Breast Cancer.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Experimental: Treatment (CD19/BCMA-CAR T cells, chemotherapy)

Treatment (CD19/BCMA-CAR T cells, chemotherapy)

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 CD19/BCMA-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 CD19/BCMA-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 CD19/BCMA-CAR T cells.
Biological: CD19- BCMA CAR-T cells

The intervention in this clinical trial involves a novel approach using CD19/BCMA-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.

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

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

Other Names:
  • EB-BH2024-2

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
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.
28 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of successful manufacture and expansion of the CD19/BCMA chimeric antigen receptor (CAR) T cells
Time Frame: 10-14 days after apheresis or thawing of cryopreserved peripheral blood mononuclear cell
satisfy the targeted dose level and meet the required release specifications outlined in the Certificate of Analysis (COA)
10-14 days after apheresis or thawing of cryopreserved peripheral blood mononuclear cell

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Essen Biotech

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 10, 2024

Primary Completion (Estimated)

December 10, 2025

Study Completion (Estimated)

December 28, 2025

Study Registration Dates

First Submitted

April 1, 2024

First Submitted That Met QC Criteria

April 1, 2024

First Posted (Actual)

April 5, 2024

Study Record Updates

Last Update Posted (Actual)

October 15, 2024

Last Update Submitted That Met QC Criteria

October 11, 2024

Last Verified

October 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ESBI202492

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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