Interleukin-2 Following 4SCAR19/22 T Cells Targeting Refractory and/or Recurrent B Cell Malignancies

March 14, 2024 updated by: Zhujiang Hospital

Anti-CD19/CD22 4th Generation CAR-T Cells (4SCAR19/22) Followed by Interleukin-2 Treating Pediatric Relapsed and Refractory B Cell Malignancies

Clinical studies of CD19 CAR-T cells in the treatment of blood and lymphatic system tumors have achieved unprecedented successes. Because of the heterogeneity of the tumor, patients often carry CD19-negative tumor cell clones that express alternative target antigens (such as CD22, CD20 and CD123). In order to effectively eradicate all tumor clones and prevent recurrence, alternative tumor antigens besides CD19 are considered for CAR-T cell targeting. In this tudy, autologous T cells are genetically modified with 4th generation anti-CD19 and anti-CD22 CARs (4SCAR19/22) using lentiviral vectors. For safety consideration, the 4SCAR is engineered with an inducible caspase 9 self-withdrawal genetic design that allows for rapid elimination of the infused CAR-T cells. Interleukin-2 has been shown to boost immune response against leukemia cells. The serum interleukin-6 level will be monitored and when it returns to normal range by day 28 after CAR-T cell infusion, patients will receive subcutaneous injection of interleukin-2, and evaluated for 24 months for safety, efficacy and persistence of CAR T cells.

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Withdrawn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

Objectives:

  1. Primary Outcome Measures:

    1. Evaluate the frequency and severity of adverse events, including, but not limited to, cytokine release syndrome (CRS) [ Time Frame: From date of dosing ( day 1 ) up to 50 weeks ]
    2. Evaluate grade 3 and higher toxicity rate of patients (toxicity possibly attributed to 4SCAR19/22 T cells)
    3. Evaluate the safety and effect of administration of 4SCAR19/22 T cells followed by interleukin-2 in treating pediatric patients with relapsed and refractory B cell malignancies.

  2. Secondary:

    1. Evaluate Overall Complete Remission Rate (ORR).
    2. Evaluate overall response rate including complete remission (CR) and complete remission with incomplete blood count recovery (CRi) .
    3. Evaluate duration of remission (DOR).
    4. To evaluate the incidence and the treatment effect of cytokine release syndrome (CRS).
    5. To determine the expansion and functional persistence of 4SCAR19/22 T cells in the peripheral blood of patients and the correlation with antitumor effects;

Design:

  1. In this single-center, open-label, nonrandomized, no control, prospective clinical trial, a total of 30 patients with resistant or refractory B cell acute lymphoblastic leukemia (ALL) or non-hodgkin's lymphoma (NHL) will be enrolled. Patients with ALL will be diagnosed according to bone marrow morphology, immunophenotype, cytogenetic and molecular examination. Patients with NHL will be diagnosed according to bone marrow morphology, biopsy pathology and imaging examination.
  2. Peripheral blood mononuclear cells (PBMC) will be obtained by apheresis, and T cells will be activated and modified to express the 4SCAR-CD19/22 gene.
  3. On Day -2 to -7, PBMC will be activated and enriched for T cells, which will be followed by 4SCAR-CD19/22 lentiviral transduction. The total culture time is approximately 5-7 days.
  4. Patients will receive lymphodepleting chemotherapy composed of cyclophosphamide and fludarabine prior to cell infusion,
  5. Participants will receive the CAR-T cells at a total dose of 0.5-5x10^6/kg.
  6. Participants will receive regular subcutaneous injection of interleukin-2 of 250,000iu/m^2 every other day for 2 weeks and then rest for 2 weeks for up to 6 months after their serum interleukin-6 levels returned to normal range from day 28 after CAR-T cell infusion.
  7. Patients will be monitored for toxicity including cytokine release syndrome, hematologic toxicities and B-cell aplasia, for response of their underlying malignancy and for CAR-T cell persistence in the blood, marrow and cerebral spinal fluid (CSF).

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 Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510282
        • 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

1 year to 14 years (Child)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Relapsed or refractory CD19+ B-cell lymphoma or leukemia.
  2. Measurable disease.
  3. Karnofsky/jansky score of 60% or greater.
  4. ≥1 years old and ≤14 years.
  5. Fertile females/males.
  6. Expected survival>12 weeks.

  7. Histologically confirmed as CD19/20-positive ALL/NHL and who meet one of the following conditions:

    1. Patients receive at least 2-4 prior combination chemotherapy regimens (not including single agent monoclonal antibody therapy) and fail to achieve CR.
    2. Recurrent disease and not eligible for allogeneic stem cell transplantation, and stable disease after therapy but refused further treatment.
    3. Disease recurrence after stem cell transplantation.
    4. Diagnosis as lymphoma, and refuse conventional treatment such as chemotherapy, radiation, stem cell transplantation and monoclonal antibody therapy.
  8. Creatinine < 2.5 mg/dl.
  9. Alanine transaminase (ALT) <3x upper limit of normal (ULN), aspartate aminotransferase (AST) <3x ULN.
  10. Bilirubin < 2.0 mg/dl.
  11. Adequate venous access for apheresis, and no other contraindications for leukapheresis.
  12. Take contraceptive measures before recruit to this trial.
  13. Written voluntary informed consent is given.

Exclusion Criteria:

  1. A history of mental illness and poorly controlled.
  2. Patients with symptoms of central nervous system.
  3. Suffering severe cardiovascular or respiratory disease.
  4. Accompanied by other malignant tumor.
  5. Known human immunodeficiency virus (HIV) infection.
  6. Active and/or severe infection (e.g. tuberculosis, sepsis and opportunistic infections, active hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection).
  7. Other serious underlying medical conditions, which, in the Investigator's judgment, could impair the ability of the patient.
  8. Taking immunosuppressive agents within 1 week due to organ transplantation or other disease which need long-lasting administration.
  9. Patients that do not consent to tissue and blood sample collection and storage in a biobank.
  10. Female study participants of reproductive potential must have a negative serum or urine pregnancy test performed 48 hours before infusion.
  11. Pregnancy and nursing females.

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: 4SCAR19/22 T cells and interleukin-2
Patients with resistant or refractory B cell acute lymphoblastic leukemia (ALL) or non-hodgkin's lymphoma (NHL) will receive CAR-T cells at a total dose of 0.5-5x10^6/kg and regular subcutaneous injection of interleukin-2 every other day for 2 weeks and then rest for 2 weeks for up to 6 months after their serum interleukin-6 levels returned to normal range from day 28 after CAR-T cell infusion.
Biological: 4SCAR19/22 T cells
CD19/CD22-targeted 4th Generation CAR-T Cell (4SCAR19/22)
Drug: Interleukin-2
Interleukin-2 of 250,000iu/m^2 every other day for 2 weeks and then rest for 2 weeks for up to 6 months.
Other Names:
  • IL-2

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
Evaluate the frequency and severity of adverse events including, but not limited to, cytokine release syndrome (CRS)
Time Frame: From date of dosing ( day 1 ) up to 50 weeks
b)Evaluate grade 3 and higher toxicity rate of patients (toxicity possibly attributed to 4SCAR19/22 T cells)
From date of dosing ( day 1 ) up to 50 weeks

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.
Shenzhen Geno-Immune Medical Institute

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: Li-hua Yang, Ph.D., Southern Medical University, China
  • Study Director: Lung-Ji Chang, Ph.D., Shenzhen Geno-immune Medical Institute

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 (Actual)

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 30, 2017

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 15, 2022

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 31, 2023

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).
March 26, 2017

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.
March 26, 2017

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.
March 31, 2017

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.
September 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.
  • anti-CD19/22 CART Cells

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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