Combination CAR-T Cell Therapy Targeting Hematological Malignancies

September 18, 2019 updated by: Lung-Ji Chang, Shenzhen Geno-Immune Medical Institute

Combination CAR-T Therapy of 4SCAR19 Plus 4SCAR20, 22, 38, 70 and 123 Targeting Hematological Malignancies

The study will evaluate safety and efficacy of a combination of 4th generation chimeric antigen receptor gene-modified T cells targeting CD19 (4SCAR19) and CD20 (4SCAR20), CD22 (4SCAR22), CD30 (4SCAR30), CD38 (4SCAR38), CD70 (4SCAR70) or CD123 (4SCAR123) for patients with B cell malignancies. Clinical response and development of a standardized lentiviral vector and cell production protocol will be investigated. This is a phase I/II trial enrolling patients from multiple clinical centers.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Background:

T cells modified with lentiviral chimeric antigen receptor (CAR) gene have been studied in different clinical settings. Recent successes suggest that increased costimulatory signaling in the CAR design is critical for long term efficacy. Several clinical reports indicate that many patients still relapse and developed CD19-negative cancer cells after CD19 targeted therapy. Thus, to prevent the target escapes and improve the therapeutic effects, CAR gene-modified T cells targeting CD20, CD22, CD30, CD38, CD70 or CD123 are considered to apply together with CD19 CAR-T cells.

Activation of T cell response to high tumor burden may induce a severe response. To increase safety, a novel design using an inducible caspase 9 fusion gene has been incorporated in the CAR gene. A 4th generation CAR lentiviral vector (4SCAR) carrying multiple costimulatory signals for CD28/CD137/CD27 plus an inducible apoptotic caspase 9 gene has been established. This study aims to evaluate the activities of a combination of CAR gene-modified T cells to target cancer cells based on specific CD19/CD20/CD22/CD30/CD38/CD70/CD123 single chain antibody gene designs (4SCAR19/20/22/30/38/70/123).

Objective:

To evaluate safety and efficacy of administrating 4SCAR19, 4SCAR20, 4SCAR22, 4SCAR30, 4SCAR38, 4SCAR70 and 4SCAR123 T cells to patients with mixed CD19 positive and negative B cell malignancies following a cyclophosphamide/fludarabine based conditioning regimen.

Eligibility:

Patients older than 6-month-old with CD19 positive or negative B cell malignancies that have recurred after or refractory to standard therapy and is deemed incurable using standard treatment.

Design:

Participants will be screened based on cancer cell phenotype analyzed using flow cytometry or immunohistochemical staining methods. Peripheral blood mononuclear cells (PBMC) will be obtained through apheresis. On Day -5 to -7, T cells from PBMC will be activated and enriched, which will be followed by 4SCAR19, 4SCAR20, 4SCAR22, 4SCAR30, 4SCAR38, 4SCAR70 and 4SCAR123 lentiviral transduction. The total cell preparation time is approximately 5-7 days. Participants will receive a preparative conditioning regimen comprising cyclophosphamide/fludarabine to prepare their immune system to accommodate the modified CAR T cells. The preparative regimen will depend on the immune condition of patients, which is consistent with standard chemotherapy conditioning regimen. Participants will receive an infusion of the modified 4SCAR19 and 4SCAR20/22/30/38/70/123 T cells and closely followed up for treatment-related responses. Participants will be continuously monitored for CAR T cells and clinical responses in a preset timeline.

Study Type

Interventional

Enrollment (Anticipated)

100

Phase

  • 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
        • Recruiting
        • Zhujiang Hospital of Southern Medical University
        • Contact:
      • Shenzhen, Guangdong, China, 518000
        • Recruiting
        • Shenzhen Geno-Immune Medical Institute
    • Yunnan
      • Kunming, Yunnan, China, 650000
        • Recruiting
        • Yunnan Cancer Hospital & The Third Affiliated Hospital of Kunming Medical University & Yunnan Cancer Center
        • Contact:

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

Ages Eligible for Study

6 months to 75 years (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. age older than 6 months.
  2. malignant B cell surface expression of CD19/CD20/CD22/CD30/CD38/CD70/CD123 molecules.
  3. the KPS score over 80 points, and survival time is more than 1 month.
  4. greater than Hgb 80 g/L.
  5. no contraindications to blood cell collection.

Exclusion Criteria:

  1. accompanied with other active diseases, the treatment is difficult to assess patient response.
  2. bacteria, fungus, or virus infection, unable to control.
  3. living with HIV.
  4. active HBV and HCV infection.
  5. pregnant and nursing mothers.
  6. under systemic steroid treatment within a week of the treatment.
  7. prior failed CAR-T treatment.

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: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: 4SCAR19 and 4SCAR20/CD22/CD30/CD38/CD70/CD123
Patients who have relapsed and refractory B cell malignancies after chemotherapy will be treated with CD19 and CD20/CD22/CD30/CD38/CD70/CD123-specific gene-engineered T cells.
Biological: 4SCAR19 and 4SCAR22
4SCAR19 and 4SCAR22
Biological: 4SCAR19 and 4SCAR38
4SCAR19 and 4SCAR38
Biological: 4SCAR19 and 4SCAR20
4SCAR19 and 4SCAR20
Biological: 4SCAR19 and 4SCAR123
4SCAR19 and 4SCAR123
Biological: 4SCAR19 and 4SCAR70
4SCAR19 and 4SCAR70
Biological: 4SCAR19 and 4SCAR30
4SCAR19 and 4SCAR30

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety of fourth generation anti CD19 and CD20/CD22/CD30/CD38/CD70/CD123 CAR-T cells in patients with relapsed B cell malignancies using CTCAE 4 standard to evaluate the level of adverse events standard to evaluate the level of adverse events
Time Frame: 24 weeks
physiological parameter (for safety, measuring cytokine response, fever, symptoms)
24 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Anti tumor activity of fourth generation anti CD19 and CD20/CD22/CD30/CD38/CD70/CD123 CAR-T cells in patients with relapsed or refractory B cell malignancies
Time Frame: 1 year
scale of CAR copies and leukemic cell burden (for efficacy)
1 year

Collaborators and Investigators

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

Sponsor

Shenzhen Geno-Immune Medical Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

July 15, 2017

Primary Completion (ACTUAL)

July 31, 2019

Study Completion (ANTICIPATED)

December 1, 2021

Study Registration Dates

First Submitted

April 19, 2017

First Submitted That Met QC Criteria

April 19, 2017

First Posted (ACTUAL)

April 24, 2017

Study Record Updates

Last Update Posted (ACTUAL)

September 19, 2019

Last Update Submitted That Met QC Criteria

September 18, 2019

Last Verified

September 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GIMI-IRB-17005

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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