Safety of Autologous Humanized Anti-CD19 and Anti-CD20 Dual Specific CAR-T Cells in Adult Patients With Diffuse Large B-cell Lymphoma

NCT04215016 | Unknown Phase 1

• 1 other identifier: CART-19-05
• 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

Relapsed or Refractory DLBCL Patients With Either CD19 or CD20 Positive

Outcome Measures

Primary Outcomes (1)

• The types and Incidence of adverse events

  Up to 12 months

Secondary Outcomes (3)

• Overall response rate

  Up to 12 months

• Progression-free survival (PFS)

  Up to 12 months

• Response duration

  Up to 12 months

Study Arms (1)

Humanized 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

Humanized anti-CD19 and CD20 bispecific autologous CAR-T cells injection: the first dose is 1.0×106 /kg, the second dose is 3.0×106 /kg, and the third dose is 8.0×106 /kg. Patients will receive lymphodepleting chemotherapy at least 1 week before CAR-T cell infusion.

Humanized 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 (primary mediastinal large B-cell lymphoma and transformed follicular lymphoma included), 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;
• According to the initial evaluation, staging and response assessment of Hodgkin's and non-Hodgkin's lymphoma -the Lugano Classification (2014), there is at least one measurable lesion at baseline;
• Life expectancy ≥12 weeks;

You may not qualify if:

• Prior treatment with any cell therapy before signing the informed consent form, including CAR-T therapy;
• 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 testicular invasion, including those who have had testicular resection;
• 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;
• Patients on oral anticoagulation therapy within 1 week of A-02 infusion;
• Prior radiation therapy 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);

Sponsors & Collaborators

• Fujian Medical University: lead

Study Sites (1)

Fujian Medical University Union Hospital

Fuzhou, Fujian, 350001, China

RECRUITING

MeSH Terms

Conditions

Recurrence

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Jianda Hu, Prof.M.D.Ph.D

CONTACT

86-13959169016; drjiandahu@163.com

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: Director of the department of Hematology

Study Record Dates

• First Submitted: December 29, 2019
• First Posted: January 2, 2020
• Study Start: December 1, 2019
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2024
• Last Updated: January 2, 2020

Record last verified: 2019-12

Locations

CN (1)