Safety, Efficacy and Pharmacokinetics of ThisCART19A in Patients With Refractory or Relapsed B Cell Lymphoma

A Single Dose-escalation Study to Evaluate the Safety, Efficacy and Pharmacokinetics of Allogeneic CAR-T Targeting CD19 in Patients With Refractory or Relapsed B Cell Lymphoma

This is a single dose escalation study to evaluate the safety, efficacy and pharmacokinetics of ThisCART19A (Allogeneic CAR-T targeting CD19) in patients with refractory or relapsed CD19 positive B cell Lymphoma.

Study Overview

• Status: Not yet recruiting
• Conditions: Allogeneic, CAR-T, Protein Sequestration, Non-gene Edited, r/r B-NHL
• Intervention / Treatment: Drug: ThisCART19A

Detailed Description

This is a single-center, nonrandomized, open-label, dose-escalation study to evaluate the safety, efficacy and pharmacokinetics of ThisCART19A in patients with refractory or relapsed CD19 positive B cell Lymphoma, such as Diffuse large B-cell lymphoma (DLBCL) , follicular lymphoma and etc.

• Study Type: Interventional
• Enrollment (Anticipated): 15
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Jun Li, Ph.D.; Phone Number: +86 18662604088; Email: jli@ctigen.com
• Study Contact Backup: Name: Mingzhi Zhang, Ph.D.; Phone Number: +86 13838565629; Email: mingzhi_zhang1@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female aged ≥ 18 years old;
2. Histologically confirmed diagnosis per WHO Classification Criteria for Lymphocytic Tumors 2017, including follicular lymphoma (FL), marginal zone lymphoma (MZL, including SMZL, NMZL and extranodal MZL), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), etc;
3. Relapsed or refractory B-cell NHL.

4. Adequate treatment :

   1. Follicular lymphoma should be treated with at least two prior treatment including alkylating agents and anti-CD20 mAbs;
   2. Marginal zone lymphoma should be treated with at least two prior treatment including anti-CD20 mAbs;
   3. mantle cell lymphoma should be treated with a first-line therapy including anthracyclines/bendamoxetine+anti-CD20 mAbs;
   4. Diffuse large B lymphoma, not otherwise specified (DLBCL, NOS), high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (double/triple hit lymphoma, DHL/THL), diffuse large B-cell lymphoma (DLBCL) transformed from follicular lymphoma (FL), histological grade 3b follicular lymphoma. relapsed or primary refractory lymphoma within 12 months after first-line treatment, first-line therapy including anthracycline and anti-CD20 mAbs.
5. Failing to autologous CAR-T therapy.
6. Estimated life expectancy > 12 weeks deemed by investigator；
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
8. At least one measurable lesion, with any nodal lesion > 15mm in the longest diameter and any extranodal lesion > 10mm in the longest diameter.
9. Adequate bone marrow, renal, hepatic, pulmonary and cardiac function;
10. Should be confirmed Cluster of differentiation(CD)19 positive by biopsy for the patient who received target CD19 therapy before.

Exclusion Criteria:

1. Allergic to preconditioning measures.
2. HP-positive MALT;
3. Patients with risks of deep gastrointestinal ulcers, perforation or gastrointestinal bleeding
4. Patients with other malignancies other than B-cell malignancies within 5 years prior to screening. Patients with cured skin squamous carcinoma, basal carcinoma, non-primary invasive bladder cancer, localized low-risk prostate cancer, in situ cervical/breast cancer can be recruited.
5. Uncontrollable bacterial, fungal and viral infection during screening.
6. Patients had pulmonary embolism (PE) and/or deep vein thrombosis (DVT) within 3 months prior to enrollment.
7. Had intolerant severe cardiovascular and cerebrovascular diseases and hereditary diseases prior to enrollment.
8. Imaging confirmed the presence of central nervous system involvement (both primary and secondary) and obvious symptoms at the time of screening.
9. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) or Human immunodeficiency virus (HIV) or Syphilis infection. HBV-DNA < 2000 IU/mL can be enrolled, but should admitted to use anti-virus drugs such as entecavir, tenofovir, etc, and supervisory the relative indication during the treatment.
10. Had big lesion(single lesion diameter ≥7.5 cm).
11. Receive allogeneic hematopoietic stem cell transplantation less than 100 days.
12. Vaccinated with influenza vaccine within 2 weeks prior to lymphodepleting chemotherapy (Severe Acute Respiratory Syndrome-Corona virus disease 19 can be included, inactivated, live/non-live adjuvant vaccinations allowed to be included) .
13. Patients who are receiving Graft versus host disease Hepatitis(GvHD) treatment; Patients without GvHD and who had stopped immunosuppressive drugs for at least 1 month were eligible for inclusion.
14. Women who are in pregnant or lactating, and female subjects or partners who plan to be pregnant within 1 year after cell infusion. Male subjects who plan pregnancy within 1 year after infusion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ThisCART19A cell injection; In this study, allogeneic anti-CD19 CART cell (This CART19A) injection is used to treat patients with refractory or relapsed CD19 positive B cell Lymphoma.	Drug: ThisCART19A; In this study, allogeneic anti-CD19 CAR-T cell (ThisCART19A) injection is used to treat patients with refractory or relapsed CD19 positive B cell Lymphoma.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose limited toxicity(DLT) observation in patient with NHL during dose escalation stage	DLT is defined as the incidence of severe adverse events related to ThisCART19A more than 33% in each dose level.	28 days
Objective Response Rate in patient with NHL during dose expansion stage	the incidence of complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), or unevaluable (UE) as best response to treatment	12 months
The incidence of all grade TEAEs and ≥3 grade TEAEs during dose escalation stage	Incidence of treatment-emergent adverse events (TEAEs) and ≥3 grade TEAEs	Up to 2 years after ThisCART19A infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS(overall survival) during dose escalation stage and expansion stage	Overall survival (OS) is defined as the time from the date of lymphodepletion until death from any cause.	12 months
Analysis the change characteristics of CART cell number and copy number during dose escalation and expansion stages	Track CAR T cells expansion in patients after infusion	6 months
Analysis the severity and Incidence of Adverse Events in each dose level during dose escalation and dose expansion stage	Including more than or equal to grade 3 adverse events graded according to the NCI CTCAE v5.0, or the adverse events with special attention	3 months
the change characteristics of immune effect cells number during dose escalation and expansion stages	Analysis the effect cells (such as CD19+ B cells、T cells、NK cells)	3 months
Analysis the change characteristics of cytokines during dose escalation and expansion stages (IL-1β/IL-2/IL-4/IL-5/IL-6/IL-8/IL-10/IL-12p70/IL-17A/IL-17F/IL-22/TNF-α/TNF-β)	cytokines including IL-1β/IL-2/IL-4/IL-5/IL-6/IL-8/IL-10/IL-12p70/IL-17A/IL-17F/IL-22/TNF-α/TNF-β	3 months
Duration of response (DOR) during dose escalation stage and expansion stage	The duration of overall response is measured from the time measurement criteria are met for complete response (CR) or partial response (PR)	12 months
Progress-free survival (PFS) during dose escalation stage and expansion stage	Progress-free survival (PFS) is defined as time from the first CAR-T cell infusion date to first documentation of PD, or death from any cause.	12 months

Collaborators and Investigators

• Sponsor: Zhengzhou University
• Collaborators: Fundamenta Therapeutics, Ltd.

Study record dates

Study Major Dates

• Study Start (Anticipated): September 2, 2022
• Primary Completion (Anticipated): July 1, 2025
• Study Completion (Anticipated): July 1, 2025

Study Registration Dates

• First Submitted: August 30, 2022
• First Submitted That Met QC Criteria: September 9, 2022
• First Posted (Actual): September 10, 2022

Study Record Updates

• Last Update Posted (Actual): September 10, 2022
• Last Update Submitted That Met QC Criteria: September 9, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: FT400-010

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