Exploratory Study of CD19-targeted Chimeric Antigen Receptor T Cells(BZ019) for Relapsed and Refractory B-cell Lymphoma

NCT04067414 | Completed Phase 1 DMC

• 1 other identifier: QT2018002
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, multicenter, dose-escalation phase 1 study to determine the safety and efficacy of BZ019 in relapsed or refractory CD19+ B-cell Lymphoma.

Conditions

Diffuse Large B Cell Lymphoma; High-grade B-cell Lymphoma; Transformed Lymphoma; Primary Mediastinal Large B Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Number of adverse events

  Number of BZ019 therapy associated adverse events, such as cytokine release syndrome(CRS), chimeric antigen receptor (CAR)-T cell related encephalopathy syndrome(CRES) or other adverse events.

  up to 1 year after BZ019 infusion.

Secondary Outcomes (2)

• proliferation of BZ019 in vivo

  up to 1 year after BZ019 infusion.

• Overall response rate

  up to 1 year after BZ019 infusion.

Study Arms (1)

BZ019 treatment

EXPERIMENTAL

Subjects will receive lymphodepleting chemotherapy of fludarabine and cyclophosphamide (flu/cy) followed by single-dose of BZ019 infusion. A 3×3 dose escalation design of BZ019 will be adopted.

Biological: BZ019

Interventions

BZ019 BIOLOGICAL

Subjects will be enrolled in three dose-groups: Dose 1: 1×10\^6/kg CAR+ cells; Dose 2: 3×10\^6/kg CAR+ cells; Dose 3: 6×10\^6/kg CAR+ cells.

BZ019 treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent must be obtained prior to any screening procedures
• Age ≥ 18 years subjects with Relapsed or refractory large B-cell lymphoma, including: DLBCL,NOS, high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, transformed B-cell lymphoma, primary mediastinal B-cell lymphoma (PMBCL).
• No response for the last chemotherapy:
• Progressive disease after the last chemotherapy or
• Stable disease after the last chemotherapy, and the maintenance time for stable disease was no longer than 6 month after last dose.
• Either having failed autologous Hematopoietic stem cell transplantation (ASCT), or being ineligible for or not consenting to ASCT
• Refractory disease after ASCT or relapsed disease within 12 months after last ASCT (histologically confirmed) or
• No response or relapsed disease for the last therapy after ASCT.
• Subjects must be accepted adequate treatment, including at least:
• Treated by CD20 monoclonal antibody (Rituximab) except for CD20 negative.
• Chemotherapy including anthracycline
• Measurable disease at time of enrollment according to the revised international working group response criteria for malignant lymphoma.
• Life expectancy ≥12 weeks
• Eastern Cooperative Oncology Group (ECOG) performance status that is either 0 or 1 at screening.
• Adequate organ function:

You may not qualify if:

• Prior treatment with any prior anti-CD19/anti-CD3 therapy, or any other anti-CD19 therapy
• Treatment with any prior gene therapy product, include CAR-T cell therapy.
• Active Central Nervous System (CNS) involvement by malignancy or secondary CNS involvement
• History or presence of clinically relevant CNS pathology such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or self-immune disease with CNS involvement.
• Prior allogeneic HSCT
• Eligible for and consenting to ASCT
• Chemotherapy other than lymphodepleting chemotherapy within 2 weeks of infusion
• Investigational medicinal product within the last 30 days prior to screening
• Prior radiation therapy within 2 weeks of infusion
• Active replication of or prior infection with hepatitis B or active hepatitis C( HCV RNA positive )
• HIV positive patients
• Uncontrolled acute life threatening bacterial, viral or fungal infection (e.g. blood culture positive ≤ 72 hours prior to infusion)
• Unstable angina and/or myocardial infarction within 6 months prior to screening
• Previous or concurrent malignancy with the following exceptions:
• Adequately treated basal cell or squamous cell carcinoma (adequate wound healing is required prior to study entry)

Sponsors & Collaborators

• Institute of Hematology & Blood Diseases Hospital, China: lead
• Shanghai Cell Therapy Engineering Technology Research Center Group Co., Ltd.: collaborator

Study Sites (1)

Institute of Hematology & Blood Diseases Hospital

Tianjin, 300020, China

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Lugui Qiu, MD

  Institute of Hematology & Blood Diseases Hospital, China

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A treatment program will include lymphodepleting chemotherapy with fludarabine and cyclophosphamide (flu/cy) followed by single-dose of BZ019 administered intravenously (IV). A 3×3 dose escalation design of BZ019 will be adopted.

Study Record Dates

• First Submitted: January 7, 2019
• First Posted: August 26, 2019
• Study Start: June 8, 2018
• Primary Completion: June 4, 2021
• Study Completion: June 4, 2021
• Last Updated: February 11, 2026

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)