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

September 9, 2022 updated by: Mingzhi Zhang, Zhengzhou University

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

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
15

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Jun Li, Ph.D.
  • Phone Number: +86 18662604088
  • Email: jli@ctigen.com

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Dose limited toxicity(DLT) observation in patient with NHL during dose escalation stage
Time Frame: 28 days
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
Time Frame: 12 months
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
Time Frame: Up to 2 years after ThisCART19A infusion
Incidence of treatment-emergent adverse events (TEAEs) and ≥3 grade TEAEs
Up to 2 years after ThisCART19A infusion

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
OS(overall survival) during dose escalation stage and expansion stage
Time Frame: 12 months
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
Time Frame: 6 months
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
Time Frame: 3 months
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
Time Frame: 3 months
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)
Time Frame: 3 months
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
Time Frame: 12 months
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
Time Frame: 12 months
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

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Zhengzhou University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Fundamenta Therapeutics, Ltd.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 2, 2022

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2025

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 30, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 9, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 10, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 10, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 9, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2022

More Information

Terms related to this study

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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