Anti-CD19/BCMA Bispecific CAR-T Cell Therapy for R/R POMES

Phase 1

• Conditions: POMES Syndrome; Relapsed and Refractory POMES Syndrome
• Interventions: Biological: anti-CD19/BCMA CAR-T cells; Drug: Fludarabine; Drug: Cyclophosphamide

• Registration Number: NCT03879382
• Lead Sponsor: Hrain Biotechnology Co., Ltd.

Brief Summary

The goal of this clinical trial is to study the feasibility and efficacy of anti-CD19/BCMA bispecific chimeric antigen receptors (CARs) T cell therapy for relapsed and refractory POMES Syndrome.

Detailed Description

Primary Objectives

1. To determine the feasibility ad safety of anti-CD19/BCMA CAR-T cells in treating patients with relapsed and refractory POMES Syndrome.

Secondary Objectives

1. To access the efficacy of anti-CD19/BCMA CAR-T cells in patients with POMES Syndrome.

2. To determine in vivo dynamics and persistency of anti-CD19/BCMA CAR-T cells.

Study Timeline

• Study Start: 2019-02-27
• Study First Submitted: 2019-03-15
• Study First Submitted QC: 2019-03-15
• Study First Posted: 2019-03-18
• Primary Completion: 2020-08-30
• Status Verified: 2021-08
• Last Update Submitted: 2021-08-05
• Last Update Posted: 2021-08-06
• Study Completion: 2022-05-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

• Expected survival > 12 weeks;
• Diagnosis of POMES Syndrome;
• The criteria for relapsed and refractory POMES Syndrome: patients previously received at least 3 different prior treatment regimens for multiple myeloma, including Alkylating agent and other protein inhibitors (eg: Bortezomib), and have disease progression in the past 60 days;
• At least 90 days after stem cell transplantation;
• Creatinine≤2.0 mg/dl;
• Bilirubin≤2.0 mg/dl;
• The ALT/AST value is lower than 2.5-fold of normal value;
• Accessible to intravenous injection, and no white blood cell collection contraindications;
• Sexually active patients must be willing to utilize one of the more effective birth control methods for 30 days after the CTL infusion. Male partner should use a condom;
• 5mg/day dose of Prednisone or other equivalent steroid hormone drugs (eg: Dexamethasone) were not used for two weeks before apheresis and CAR-T infusion;
• Able to understand and sign the Informed Consent Document.

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Exclusion Criteria

• • In the first 5 years before screening, there are malignant tumors other than POMES Syndrome, except for fully treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, local prostate cancer after radical surgery，and catheter carcinoma in situ after radical surgery;

  • Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive and peripheral blood HBV DNA titer higher than the upper limit of detection; hepatitis C virus (HCV) antibody positive and peripheral blood HCV RNA positive; human immunodeficiency Viral (HIV) antibody positive; Positive syphilis test;
  • Any unstable systemic disease including, but not limited to, active infection (except for local infection), unstable angina pectoris, cerebrovascular accident or transient cerebral ischemia (within 6 months prior to screening), myocardial infarction (within 6 months prior to screening), congestive heart failure (New York Heart Association [NYHA] classification ≥ III), severe arrhythmia, liver, kidney or metabolic disease requiring medication;
  • Any other diseases could affect the outcome of this trial;
  • Any affairs could affect the safety of the subjects or outcome of this trial;
  • Pregnant or lactating women, or planned pregnancy during treatment or within 1 year after treatment, or a male subject whose partner plans pregnancy within 1 year of their cell transfusion;
  • Active or uncontrollable infection requiring systemic therapy within 14 days prior to enrollment;
  • Subjects who are receiving systemic steroid treatment and requiring long-term systemic steroid treatment during the treatment as determined by the investigator before screening (except inhalation or topical use); And subjects treated with systemic steroids (except inhalation or topical use) within 72h prior to cell transfusion;
  • Received CAR-T treatment or other gene therapies before enrollment;
  • Patients with symptoms of central nervous system or brain metastasis or have received treatment for central nervous system or brain metastasis (radiotherapy, surgery or other treatment) within 3 months before enrollment;
  • Subject suffering disease affects the understanding of informed consent or comply with study protocol;
  • The investigators consider other conditions unsuitable for enrollment.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
anti-CD19/BCMA CAR-T cells	anti-CD19/BCMA CAR-T cells	Administration with anti-CD19/BCMA CAR-T cells in the relapsed and refractory POMES Syndrome patients
anti-CD19/BCMA CAR-T cells	Cyclophosphamide	Administration with anti-CD19/BCMA CAR-T cells in the relapsed and refractory POMES Syndrome patients
anti-CD19/BCMA CAR-T cells	Fludarabine	Administration with anti-CD19/BCMA CAR-T cells in the relapsed and refractory POMES Syndrome patients

Primary Outcome Measures

Name	Time	Method
Safety measured by occurrence of study related adverse effects defined by NCI CTCAE 4.0	6 months	Safety measured by occurrence of study related adverse effects defined by NCI CTCAE 4.0

Secondary Outcome Measures

Name	Time	Method
Duration of CAR-positive T cells in circulation	6 months	Duration of CAR-positive T cells in circulation
Overall complete remission rate defined by the standard response criteria for POMES Syndrome	8 weeks	Overall complete remission rate defined by the standard response criteria for POMES Syndrome

Trial Locations

Locations (1)

Shanghai Changzheng Hospital; 🇨🇳 Shanghai, Shanghai, China