Efficacy and Safety Evaluation of PD1-BCMA-CART

Clinical Study of the Safety and Efficacy of Non-viral Site-directed Integrated PD1-BCMA-CART in Adult Treatment of Relapsed or Refractory Multiple Myeloma

This trial aims to evaluate the safety and efficacy of PD1-BCMA-CART in treating patients with relapsed or refractory multiple myeloma.

Using gene editing, chimeric antigen receptors recognizing BCMA were integrated into subject self-derived T cells to obtain a large number of BCMA-CART by in vitro amplification, and BCMA-CART back into the subjects could identify and kill myeloma cells in the subjects.This open-label, dose-escalation study was designed to evaluate the safety and antitumor efficacy of PD1-BCMA-CART in the treatment of relapsed or refractory multiple myeloma.

Inclusion Criteria:

• Have the capacity to give informed consent;

• Confirmed diagnosis of active MM as defined by NCCN and IMWG criteria;

• Have a diagnosis of BCMA+ multiple myeloma (MM), (≥ 5% BCMA+ in CD138+ plasma cells by flow cytometry obtained within 45 days of study enrollment);

• Refractory and relapsed MM patients after > 2 cycles of induction therapy,or,have relapsed or treatment refractory disease following autologous stem cell transplant (ASCT);

• ECOG score=0-2.

• Subjects according with any of the following options:

  • Age≥50;
  • Failure with separation of T cells during autologous CART processing; or,
  • Failure with expansion of autologous CART; or,
  • The proportion of T cells in PBMC <10%; or,
  • Won't benefit from autologous CART therapy because of disease progress.

Exclusion Criteria:

• Pregnant or nursing women; Women of reproductive potential must have a negative serum pregnancy test performed within 48 hours of starting conditioning chemotherapy
• Active infection, HIV infection, syphilis serology reaction positive;
• Active hepatitis B, hepatitis C at the time of screening
• Significant hepatic dysfunction as following, SGOT(serum glutamic-oxaloacetic transaminase)> 5 x upper limit of normal; bilirubin > 3.0 mg/dL;
• Lymphotoxic chemotherapeutic agents within 2 weeks of leukapheresis
• serious mental disorder;
• With severe cardiac, liver, renal insufficiency, diabetes and other diseases;
• Participate in other clinical research in the past three months; previously treatment with any gene therapy products
• Contraindication to cyclophosphamide or fludarabine chemotherapy