4SCAR-T Therapy Post CD19-targeted Immunotherapy

4SCAR-T Therapy After Anti-CD19 Immunotherapy Targeting B Cell Acute Lymphoblastic Leukemia

This study will evaluate safety and efficacy of a combination of 4th generation chimeric antigen receptor gene-modified T cells (4SCAR-T) targeting CD19-negative B-ALL that express alternative surface antigens such as CD22, CD10, CD20, CD38, and CD123, as many patients relapse after anti-CD19 immunotherapy. Clinical response and optiminzation 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: Recruiting
• Conditions: CD19 Negative B-cell Malignancies
• Intervention / Treatment: Biological: Infusion of 4SCAR-T specific to CD22/CD123/CD38/ CD10/CD20

Detailed Description

Anti-CD19 immunotherapy based on antibody conjugated drugs or CD19-CAR-T cells has demonstrated unprecedented positive response in relapsing/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL). However, many patients still relapse and up to 30-50% of those relapses are characterized by the loss of CD19 surface antigen. Patients with CD19-negative relapse usually have a poor prognosis. The mechanisms underlying CD19-negative relapses are not fully understood and it is important to develop solutions to supplement post-CD19 immunotherapies.

Potential markers for recurrent leukemic blasts in an emerging CD19-negative blast population include many known B-cell lineage antigens. To prevent further target escape and improve the therapeutic effects, the 4th generation CAR gene-modified T cells targeting CD22, CD10, CD20, CD38, or CD123 have been considered in post anti-CD19 treatment. This study aims to evaluate safety and efficacy of administrating one or multiple non-CD19 targeting CAR-T cells to patients with CD19-escaped B cell malignancies.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Lung-Ji Chang, phD; Phone Number: +86-0755-8672-5195; Email: c@szgimi.org

Study Locations

• China
  • Guangdong
    • Shenzhen, Guangdong, China, 518000
      • Recruiting
      • Shenzhen Children's Hospital
      • Contact: Lichun Xie, MD; Phone Number: 86-19925192721; Email: xielichunst@sina.com
    • Shenzhen, Guangdong, China, 518107
      • Recruiting
      • The Seventh Affilliated Hospital, Sun Yat-Sen University
  • Hebei
    • Shijiazhuang, Hebei, China
      • Recruiting
      • Shijiazhuang Zhongxi Children Hospital
      • Contact: Guangming Qiao, MD; Phone Number: +86-13731113069

Participation Criteria

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. B cell malignancies relapsed after anti-CD19 immunotherapy.
3. Malignant B cells expressing one or more of the following surface molecules: CD22/CD123/CD38/CD10/CD20.
4. The KPS score over 80 points, and survival time is more than 1 month.
5. Greater than Hgb 80 g/L.
6. No contraindications to blood cell collection.

Exclusion Criteria:

1. Complications with other active diseases, and difficult to assess patient response.
2. Bacterial, fungal, or viral infection unable to control.
3. Living with HIV.
4. Active HBV and HCV infection.
5. Pregnant and nursing mothers.
6. Under systemic steroid use within a week of the treatment.
7. Judged difficult to cooporate for continued evaluation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 4SCAR-CD22/CD123/CD38/CD10/CD20 infusion; Patients who have relapsed after anti-CD19 immunotherapy or have CD19 negative B cell malignancies	Biological: Infusion of 4SCAR-T specific to CD22/CD123/CD38/ CD10/CD20; Patients who have relapsed after anti-CD19 immunotherapy or have CD19 negative B cell malignancies

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of fourth generation anti-CD22/CD123/CD38/CD10/CD20 CAR-T cells	Treatment-related adverse events are assessed by NCI CTCAE V4.0 criteria.	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-tumor activity of fourth generation anti-CD22/CD123/CD38/CD10/CD20 CAR-T cells	Scale of CAR copies are detected by qPCR and leukemic cell burden are assessed by flow cytometry	1 year

Collaborators and Investigators

• Sponsor: Shenzhen Geno-Immune Medical Institute
• Collaborators: The Seventh Affiliated Hospital of Sun Yat-sen University; Shenzhen Children's Hospital; ShiJiaZhuang Zhongxi Children Hospital

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): June 1, 2020
• Primary Completion (ANTICIPATED): May 31, 2023
• Study Completion (ANTICIPATED): December 31, 2023

Study Registration Dates

• First Submitted: June 9, 2020
• First Submitted That Met QC Criteria: June 10, 2020
• First Posted (ACTUAL): June 12, 2020

Study Record Updates

• Last Update Posted (ACTUAL): June 12, 2020
• Last Update Submitted That Met QC Criteria: June 10, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: 4S CAR-T CD22; 4S CAR-T CD123; 4S CAR-T CD38; 4S CAR-T CD10; 4S CAR-T CD20; CD19 Negative B cell leukemiaB-ALL
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: GIMI-IRB-20008

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