CD19 CAR T-cell Target Relapsed/Refractory Acute B Cell Leukemia/Lymphoma (CAR19T2)

March 14, 2024 updated by: Zhujiang Hospital

Humanized CAR19T2 T Cell in Children With Refractory/Relapsed B-cell Leukemia/Lymphoma

This study aims to evaluate the safety and efficacy of humanized Anti-CD19 Chimeric Antigen Receptor-T cell (CAR19T2 T cell) in children with refractory/relapsed B-cell acute lymphoblastic leukemia/lymphoma.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

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

CD19 CAR-T cells treating B-cell hematological malignancies have achieved unprecedented success. In this study, we investigated new third-generation autologous T cells (CAR19T2 T cells) genetically modified with humanized anti-CD19 construct incorporating CD28 and Toll-like receptor 2 (TLR2) costimulatory domains. CAR19T2 T cells will be modified before the infusion to those which could identify and kill the tumor cells (CD19+ cells). This study aims to evaluate the safety and efficacy of humanized Anti-CD19 Chimeric Antigen Receptor T cell (CAR19T2 T Cell) in children with refractory/relapsed B-cell acute lymphoblastic leukemia/lymphoma.

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

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 2
  • 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.

Study Contact Backup

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China
        • Guangdong Zhaotai Cell Bio-tech Co., LTD
      • Guanzhou, Guangdong, China
        • Zhujiang Hospital of Southern Medical University

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

2 years to 14 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. ≥1 year old and ≤18 years.
  2. Patients with relapsed and/or refractory CD19-positive B-cell acute leukemia/lymphoma.
  3. Leukemia/lymphoma relapsed after allogeneic hematopoietic stem cell transplantation within four weeks, all immunosuppressive agents were stopped for at least four weeks, and no active graft-versus-host disease(GVHD) was detonated.
  4. Lansky play (≤16 years old) scale ≥60% or Karnofsky (>16 years old) score ≥60% and Eastern Cooperative Oncology Group (ECOG) performance status ≤1. Patients who are unable to walk because of paralysis, but who are up in a wheelchair will be considered ambulatory to assess the performance score.
  5. Adequate vascular access leukapheresis procedure. Absolute Lymphocyte count (ALC) greater than or equal to 100 cells/μL.

  6. Adequate renal, hepatic, pulmonary, and cardiac function is defined as the following:

    • Serum alanine aminotransferase/aspartate aminotransferase (ALT/AST) ≤ 5 upper limit of normal (ULN), Total bilirubin ≤2 x ULN.
    • A serum creatinine based on age/gender as follows: 1 to < 2 years: maximum serum creatinine 0.6 mg/dL (both male and female);2 to < 6 years: maximum serum creatinine 0.8 mg/dL (both male and female); 6 to < 10 years: maximum serum creatinine 1 mg/dL (both male and female); 10 to < 13 years: maximum serum creatinine 1.2 mg/dL (both male and female); 13 to < 16 years: maximum serum creatinine 1.5 mg/dL (male), 1.4 mg/dL (female); >=16 years: maximum serum creatinine 1.7 mg/dL (male), 1.4 mg/dL (female).
    • Baseline oxygen saturation > 92% on room air.
    • Echocardiogram or left ventricular ejection fraction (LVEF) greater than or equal to 45% confirmed by echocardiogram, no evidence of pericardial effusion (except trace or physiological), and no clinically significant arrhythmias.
  7. Life expectancy of greater than or equal to 3 months.
  8. Patients or legal guardians must sign an informed consent.

Exclusion Criteria:

  1. Prior received any other CAR T cell and tumor vaccine treatment.
  2. Patient with a previous history of active hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection.
  3. Patient with uncontrolled systemic fungal, bacterial, viral, or other infection (including tuberculosis) despite appropriate antibiotics or other treatment.
  4. Acute GVHD grade II-IV (Glucksberg criteria) or chronic GVHD requiring systemic treatment within 4 weeks before enrollment.
  5. History or presence of any CNS disorder such as a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, etc. (Except for CNS involvement of underlying hematological malignancy)
  6. Severe psychological disorder or psychiatric illness.
  7. Combined with life-threatening severe organ failure.
  8. Major non-medicinal surgery within four weeks.
  9. Received other clinical trials within four weeks. 10. Women who are pregnant or breastfeeding.

11. The following drugs patients must be stopped prior to leukapheresis:

  • Tyrosine Kinase Inhibitor (TKI) must be discontinued more than or equal to 3 days before collection.
  • Salvage chemotherapy must be stopped > 2 weeks and intrathecal chemotherapy in the 7 days prior to collection.
  • Systemic steroid therapy exceeding the equivalent of 0.5 mg/kg/day of methylprednisolone in the 7 days before collection.
  • Donor lymphocyte infusions (DLI) and Immunosuppressive therapies within 4 weeks before collection.
  • Received clofarabine or cladribine within 3 months prior to collection.

  • Receive blinatumomab within 4 weeks, inotuzumab ozogamicin, and rituximab within 4 months, and alemtuzumab within 6 months before collection.

    12. Tyrosine Kinase Inhibitor within 1 week and asparaginase within 4 weeks prior to CAR T-cell infusion.

    13. In the opinion of the PI, patients are present for any condition, not for enrollment.

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: humanized CAR19T2 T cell to B-cell acute lymphoblastic leukemia/lymphoma
Patients received fludarabine and cyclophosphamide (Flu/Cy) for lymphodepletion (Cy at 300-500 mg/m2/dose for four days and Flu at 20-30 mg/m2/dose for two days) before CAR19T2 T cells administration. This CAR19T2 T cell will be infused over 30 minutes on days Day 0.
Biological: CD19 CAR T-Cell(CAT19T2)
Drug: Fludarabine， Administered intravenously Drug: Cyclophosphamide， Administered intravenously

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
Overall response rate
Time Frame: 3 months
A total number of patients achieved a Complete response (CR) or CR with incomplete blood count recovery (CRi) on Day 28 and three months by an independent review committee(IRC) assessment, as evaluated by peripheral blood, bone marrow, central nervous system (CNS) symptoms, physical exam (PE), and cerebrospinal fluid(CSF).
3 months
The maximum tolerated dose(MTD) of CAR19T2 T cells
Time Frame: 24 weeks
The maximum tolerated dose(MTD) of CD19-positive relapsed/ refractory acute leukemia/lymphoma treated with CAR19T2 T cells.
24 weeks
Adverse Events (AEs)
Time Frame: 3 years
Type, frequency and severity of adverse events (AEs), serious adverse events (SAE), and laboratory abnormalities (overall and in clinical, histological and molecular subgroups).
3 years

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
Minimal residual disease (MRD) negative response rate
Time Frame: Up to 12 months after infusion
Patients achieving CR or CRi and a negative MRD bone marrow.
Up to 12 months after infusion
Event-free survival (EFS)
Time Frame: Up to 3 years after infusion
Time from CAR19T2 T cell infusion to progressive disease (PD), disease relapse, start of a new anticancer therapy, or death from any cause, whichever occurs first.
Up to 3 years after infusion
Overall survival (OS)
Time Frame: Up to 3 years after infusion
Time from CAR19T2 T cell infusion to time of death due to any cause.
Up to 3 years after infusion
CAR-T cell expansion level
Time Frame: 24 months
Copies numbers of CAR in peripheral blood (PB) and/or bone marrow (BM), CSF and lymph nodes, etc.
24 months
The duration of CAR T cell persistence
Time Frame: 24 months
The duration of CAR T cell persistence in peripheral blood(PB) and/or bone marrow(BM), CSF and lymph nodes, etc.
24 months
Rate of hematopoietic stem cell transplant (HSCT) after CAR19T2 T cell infusion
Time Frame: Up to 3 years after CAR19T2 T infusion
Percentage of subjects who achieve a response after CAR19T2 T cell infusion and then proceed to HSCT.
Up to 3 years after CAR19T2 T infusion
Maximum concentration of CAR19T2 T cell and cytokines.
Time Frame: 12 months
Pharmacokinetics of CAR19T2 T cell in Maximum concentration.
12 months
Time to peak concentration of CAR19T2 T cell and cytokines.
Time Frame: 12 months
Pharmacokinetics of CAR19T2 T cell in Time to peak concentration.
12 months
Area under the curve of CAR19T2 T cell and cytokines.
Time Frame: 12 months
Pharmacokinetics of CAR19T2 T cell in Area under the curve.
12 months
Incidence of hypogammaglobulinaemia
Time Frame: 12 months
Incidence and duration of hypogammaglobulinaemia.
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.
Zhujiang Hospital

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.
Guangdong Zhaotai Cell Bio-tech Co., LTD

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Lihua Yang, Zhujiang Hospital

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 (Estimated)

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.
December 1, 2022

Primary Completion (Estimated)

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.
December 1, 2025

Study Completion (Estimated)

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.
December 1, 2028

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).
October 13, 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.
November 4, 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.
November 14, 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.
March 18, 2024

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.
March 14, 2024

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.
October 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

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.
  • 2022-KY-094

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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