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.

Study Overview

• Status: Not yet recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Biological: PD1-BCMA-CART

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 9
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: wei Li, PhD; Phone Number: +8618621670308; Email: adamweili@126.com

Study Locations

• China
  • Henan
    • Zhengzhou, Henan, China, 450052
      • First Affliated Hospital of Zhengzhou University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

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: PD1-BCMA-CART; Each subject will accept one of the following dosages of PD1-BCMA-CART cells intravenously (IV) on day 0: 0.5-2*10^6/KgBW.	Biological: PD1-BCMA-CART; Single infusion of PD1-BCMA-CART administered intravenously (i.v.)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	Proportion of patients in whom a response among complete response or partial response, as defined by International Myeloma Working group(IMWG) response criteria , will be observed.	Up to 90 days after T cell infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and Severity of Adverse Events as a Measure of Safety and Tolerability	Adverse events assessed according to NCI-CTCAE v5.0 criteria	Up to 35 days after T cell infusion
Duration of persistence of PD1-BCMA-CART	Detect the duration of PD1-BCMA-CART after injection using FACS or Q-PCR	Baseline up to 2 year

Collaborators and Investigators

• Sponsor: Bioray Laboratories
• Collaborators: The First Affiliated Hospital of Zhengzhou University
• Investigators: Principal Investigator: Yi Zhang, Professor, First Affliated Hospital of Zhengzhou University

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2024
• Primary Completion (Estimated): January 1, 2025
• Study Completion (Estimated): October 1, 2025

Study Registration Dates

• First Submitted: January 27, 2022
• First Submitted That Met QC Criteria: March 24, 2022
• First Posted (Actual): April 4, 2022

Study Record Updates

• Last Update Posted (Actual): January 5, 2024
• Last Update Submitted That Met QC Criteria: January 4, 2024
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: 2021-BRL-202

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