A Single-center Clinical Study to Evaluate the Safety, Tolerability, and Efficacy of LCAR-L10D Cell Formulations Targeting CD19 and CD22 in Patients With CD19- and/or CD22-Positive Relapsed/Refractory B-cell Lymphoma

NCT03593109 | Terminated Phase 1

• 1 other identifier: Legend-CART-201803-Ⅱ
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, single-arm, single-center, open-label, single-dose dose finding and expansion study to evaluate the safety, tolerability, pharmacokinetics, and anti-tumor efficacy profile of LCAR-L10D in subjects with CD19- and/or CD22-positive relapsed/refractory B-cell lymphoma after prior adequate standard of care.

Conditions

Lymphoma, B-Cell

Keywords

Chimeric Antigen Receptor T cells; CD19 and CD22

Outcome Measures

Primary Outcomes (2)

• Type, incidence and severity of dose-limiting toxicities (DLTs) and treatment-emergent adverse events (TEAEs)

  Dose-limiting toxicity (DLT) refers to a drug-related toxicity during treatment with the drug, the severity of which is clinically unacceptable, limiting the further escalation of drug dose. An adverse event refers to any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product (investigational or non-investigational), which does not necessarily have a causal relationship with the treatment

  Day 1-90 days after injection

• Chimeric Antigen Receptor T（CAR-T）Positive Cell Concentration

  Venous blood samples will be collected for measurement of CAR-T positive cellular concentration

  Day 1-90 days after injection

Secondary Outcomes (7)

• Recommended phase 2 dose (RP2D) of this cell therapy

  Day 1-90 days after injection

• Overall response rate (ORR) after administration

  2 years post infusion

• Duration of remission (DOR) after administration

  2 years post infusion

• Progress Free Survival (PFS) after administration

  2 years post infusion

• Overall Survival (OS) after administration

  2 years post infusion

Study Arms (1)

LCAR-L10D treatment group

EXPERIMENTAL

In LCAR-L10D treatment group, patients will be treated with dual specificity CD19 and CD22 CAR-T cells with a escalation approach, 3 CAR-T dosage will be tested in this study: 0.5×10\^6, 1.5×10\^6, 5.0×10\^6 CAR-T cells/kg.

Drug: Dual Specificity CD19 and CD22 CAR-T Cell Immunotherapy

Interventions

Dual Specificity CD19 and CD22 CAR-T Cell Immunotherapy DRUG

Patients will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) for the production of CAR-T cells. After a pre-treatment lymphodepletion therapy, patients will receive the Dual Specificity CD19 and CD22 CAR-T Cell Immunotherapy by intravenous injection.

LCAR-L10D treatment group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Volunteer to participate in the clinical study; fully understand and be informed of the information on this study, and sign the written Informed Consent Form (ICF); willing to follow and able to complete all trial procedures.
• According to the criteria for B-cell lymphoma defined in the National Comprehensive Cancer Network (NCCN) Guidelines for Lymphoma (5th edition 2018), and with CD19- and/or CD22-positive lymphoma cells detected by flow cytometry or immunohistochemistry;
• Must have at least 1 evaluable or measurable lesion meeting Lugano 2014 criteria \[Evaluable lesions: Fluorodeoxyglucose/positron emission tomography (FDG/PET) showed increased local uptake in lymph nodes or extranodal sites (higher than the liver), and PET and/or computed tomography (CT) findings are consistent with lymphoma manifestations. Measurable lesions: defined as nodule lesions with a long diameter greater than 15 or extranodal lesions with a long diameter greater than 10 mm (if the only measurable lesion has been previously treated with radiation therapy, the evidence of radiographic progression after radiation therapy is required), with increased FDG uptake). Absence of measurable lesion and diffuse increase of hepatic FDG uptake should be excluded.
• Relapsed/refractory BCL (meet one of the following conditions):
• Subjects in this category had received at least two cycles of two or more lines of standard of care and had been evaluated for best clinical response per Lugano 2014 at the time of enrollment: (one of the following conditions are met)
• The subject had a best clinical response of PD after the most recent standard chemotherapy;
• The subject had a best clinical response of SD after the most recent standard chemotherapy, but PD occurred when SD persisted for less than 6 months;
• Recurrence or progression within ≤ 12 months after autologous hematopoietic stem cell transplantation;
• In one of the following situations, the benefit of the subject may outweigh the risk as judged jointly by the investigator and the partner:
• The subject had received at least two lines of standard of care, and the best response after the most recent standard chemotherapy was SD, which persisted for less than 6 months, and the evaluable or measurable disease was larger than before but did not achieve PD;
• The subject had received at least two lines of standard of care, and the best response after the most recent standard chemotherapy was partial response (PR) or higher, but persisted for less than 6 months before progression;
• The subject had received at least two lines of standard of care and was intolerant to the most recent chemotherapy.
• All subjects must have received standardized treatment regimens with anti-CD20 monoclonal antibodies (except for those with CD20-negative tumors as determined by the investigator) and anthracyclines. For standardized treatment regimens, please refer to the criteria in the NCCN Guidelines for B-cell Lymphoma (version 5, 2018);
• Male or female, aged 18-75 years at the time of signing the ICF;
• Primary laboratory test values met the following criteria to demonstrate adequate organ and bone marrow function without severe hematopoietic abnormalities and heart, lung, liver, renal dysfunction and immunodeficiency:

You may not qualify if:

• Subjects who have received any CART cell therapy or other genetically modified T cell therapy;
• Previous allogeneic stem cell transplantation.
• Have been diagnosed or treated with other aggressive malignancies other than B-cell lymphoma, with the following exceptions:
• Malignant tumors that have been treated radically, and no known active disease within ≥ 2 years prior to enrollment; or
• Non-melanoma skin cancers have been adequately treated without symptom of disease.
• Previous anti-tumor therapy (prior to apheresis) as follows:
• Targeted therapy, epigenetic therapy, or investigational drug within 14 days or at least 5 half-lives (whichever is shorter), or has used an invasive investigational medical device.
• Cytotoxic drugs within 14 days.
• Immunomodulator within 7 days.
• Monoclonal antibodies to treat BCL within 21 days.
• Radiation therapy within 14 days.
• Positive for any one of hepatitis B surface antigen (HBsAg), hepatitis B virus deoxyribonucleic acid (HBV DNA), hepatitis C antibody (HCV-Ab), hepatitis C virus ribonucleic acid (HCV RNA), or human immunodeficiency virus antibody (HIV-Ab)
• The following cardiac disorders occurred:
• New York Heart Association (NYHA) phase III or IV congestive heart failure;
• Myocardial infarction or coronary artery bypass graft (CABG) ≤ 6 months prior to enrollment;

Sponsors & Collaborators

• Second Affiliated Hospital of Xi'an Jiaotong University: lead
• Nanjing Legend Biotech Co.: collaborator

Study Sites (1)

Second Affiliated Hospital of Xi'an Jiaotong University

Xi'an, Shaanxi, 710000, China

Location

MeSH Terms

Conditions

Lymphoma, B-Cell

Condition Hierarchy (Ancestors)

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

Study Officials

• Aili He, MD, PhD

  Second Affiliated Hospital of Xi'an Jiaotong University

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: July 7, 2018
• First Posted: July 19, 2018
• Study Start: May 30, 2019
• Primary Completion: May 1, 2021
• Study Completion: May 1, 2021
• Last Updated: November 1, 2021

Record last verified: 2020-11

Locations

CN (1)