An Exploratory Clinical Trial of Autologous Humanized Anti-cluster of Differentiation Antigen 19/20(CD19/CD20) Dual Specific CAR-T Cells Injection

NCT04486872 | Unknown Phase 1

• 1 other identifier: A-02 POC-01
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-arm, open-label, dose escalation, phase I study, aiming to evaluate the safety and efficacy of Autologous Humanized Anti-CD19 and Anti-CD20 Dual Specific Chimeric Antigen Receptor (CAR) T-cells in patient with relapsed or refractory diffuse B cell lymphoma.

Conditions

Diffuse Large B Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• The types and Incidence of adverse events

  Adverse events at each visit with the NCI CTCAE v5.0 used as a guide for the grading of severity.

  Up to 12 months

Secondary Outcomes (5)

• Duration of overall response

  Up to 12 months

• Overall survival

  Up to 12 months

• Progression-free survival

  Up to 12 months

• Objective response rate

  Up to 12 months

• Duration of response

  Up to 12 months

Study Arms (1)

anti-CD19 and anti-CD20 dual specific CAR-T Cells

EXPERIMENTAL

Biological: Autologous humanized anti-CD19 and anti-CD20 dual specific CAR-T Cells

Interventions

Autologous humanized anti-CD19 and anti-CD20 dual specific CAR-T Cells BIOLOGICAL

Autologous Humanized Anti-CD19 and Anti-CD20 Dual Specific CAR-T Cells injection. Within 3 to 5 days after the pretreatment, the subjects received a single A-02 reinfusion, the infusion dose of each group of subjects 1.00 × 10\^6/kg, 3.00 × 10\^6/kg or 5.00 × 10\^6/kg (if applicable), it is recommended to complete the infusion within 30 min after cell recovery.

anti-CD19 and anti-CD20 dual specific CAR-T Cells

Eligibility Criteria

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

You may qualify if:

• The subject or her/his legally guardian(s) must sign the informed consent form approved by the Institutional Ethics Committee (IEC) prior to any screening procedures;
• Subjects aged 18 years or older with relapsed or refractory DLBCL (including primary mediastinal large B-cell lymphoma and transformed follicular lymphoma), of which refractory is defined as:
• Have no response to the recent treatment including:
• The best response to the treatment regimen is progressive disease (PD) ,or;
• stable disease(SD) which maintained less than 6 months after the last treatment, or;
• not suitable for autologous hematopoietic stem cell transplantation (ASCT), or ASCT refractory, including:
• progressive disease after ASCT or relapse within 12 months (relapse must be confirmed by biopsy), or;
• If remedial treatment is given after ASCT, the subject must have no response or relapse after the last treatment.
• Subjects who have previously received ≥2 lines treatment, and at least including:
• Anti-CD20 monoclonal antibody(rituximab), unless the CD20 negative;
• A chemotherapy regimen containing anthracyclines;
• The DLBCL patients who transformed from follicular lymphoma must have previously received chemotherapy for follicular lymphoma and have developed chemotherapy-refractory diseases after transform to DLBCL.
• Confirmation for either CD19 or CD20 positivity using immunohistochemistry or flow cytometry(accepting the previous results from the a third-level grade A hospitals before the collection of peripheral blood mononuclear cells or peripheral blood. For CD20 positive only, the investigator needs to determine whether the treatment benefit);
• According to the preliminary assessment of Hodgkin's lymphoma and non-Hodgkin's lymphoma, staging and response assessment recommendations (2014 version), there is at least one measurable lesion at baseline;
• If the subject has received a single target in the past, such as CD19-CAR cell therapy, it must be confirmed that the disease has progressed or relapsed after treatment and is at least 1 month from the planned single collection period

You may not qualify if:

• Subjects who meet any of the following criteria will not be enrolled:
• Subjects who have received any CD19/CD20 dual-target cell therapy products before signing the informed consent form;
• Subjects with detectable cerebrospinal fluid malignant cells or brain metastases, or with a history of central nervous system (CNS) lymphoma or primary CNS lymphoma;
• Subjects with current or previous history of central nervous system disease, such as seizures, cerebral ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease involving the central nervous system;
• Subjects who have previously received allogeneic hematopoietic stem cell transplantation (HSCT); or suitable and consenting to Autologous hematopoietic stem cell transplantation (ASCT);
• Chemotherapy other than lymphodepleting chemotherapy within 2 weeks of A-02 infusion;
• Investigational medicinal product within the last 30 days prior to sign the informed consent form;
• Subjects with active hepatitis B（defined as hepatitis B surface antigen positive, or hepatitis B core antibody positive with hepatitis B virus DNA detection value \> 1000 copies/ml）or hepatitis C(HCV RNA positive);
• Subjects positive for HIV antibody or treponema pallidum antibody;
• Uncontrolled acute life threatening bacterial, viral or fungal infection (e.g. blood culture positive ≤ 72 hours prior to A-02 infusion);
• Unstable angina and/or myocardial infarction within 6 months prior to sign the informed consent form;
• Previous or concurrent malignancy with the following exceptions:
• Adequately treated basal cell or squamous cell carcinoma (adequate wound healing is required prior to sign the informed consent form);
• In situ carcinoma of the cervix or breast, treated curatively and without evidence of recurrence for at least 3 years prior to sign the informed consent form;
• A primary malignancy which has been completely resected and in complete remission for ≥ 5 years;

Sponsors & Collaborators

• First Affiliated Hospital of Zhejiang University: lead

Study Sites (1)

First Affiliated Hospital of Zhejiang University

Hangzhou, Zhejiang, 310009, China

RECRUITING

Related Publications (1)

• Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.

  PMID: 34515338 DERIVED

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

Central Study Contacts

Jie Jin, Prof

CONTACT

13505716779; jiej0503@163.com

Jianzhong Shentu, Prof

CONTACT

13957111817; stjz@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof

Study Record Dates

• First Submitted: July 17, 2020
• First Posted: July 27, 2020
• Study Start: July 25, 2020
• Primary Completion: May 11, 2022
• Study Completion: June 25, 2022
• Last Updated: August 26, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)