Anti-CD22 Chimeric Antigen Receptor (CAR)-Modified T Cell Therapy for Relapsed Refractory B-cell Malignancies

August 5, 2019 updated by: MEI HENG, Wuhan Union Hospital, China

Efficacy and Safety of Anti-CD22 CAR-T Therapy in Patients With Relapsed/Refractory B-cell Malignancies: a Single-center, Open-label, Single-arm Clinical Study

This is a single-center, open-label, single-arm study to evaluate the safety and efficacy of anti-CD22 CAR-T cells in patients with relapsed or refractory B-cell Malignancies.

Study Overview

Detailed Description

Chimeric antigen receptor (CAR)-modified T cells (CAR-T cells) have the capabilities to recognize tumor associated antigen and kill tumor cells specifically. CAR-T therapy showed great effect on patients with relapsed or refractory B-cell malignancies. CAR consists of single chain variable fragment (scFv) and activation domain of T cell. In preclinical study, the researchers constructed a third generation CAR containing CD137 and CD28 costimulatory domains.

This study aims to evaluate the safety and effectiveness of anti-CD22 CAR-T cells in patients with relapsed or refractory B-cell Malignancies.

Study Type

Interventional

Enrollment (Anticipated)

50

Phase

  • 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

    • Hubei
      • Wuhan, Hubei, China, 430022
        • Recruiting
        • Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

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

14 years to 70 years (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Patient or his or her legal guardian voluntarily participates in and signs an informed consent form.
  2. Male or female patients aged 14 to 70 years (including 14 and 70 years old).
  3. Pathological and histological examination confirmed CD22+ B-cell malignancies, and patients met the following criteria for refractory or relapsed B-cell malignancies.

    A.Refractory/relapsed B-cell lymphoblastic leukemia (Meeting one of the following)

    i. Recurrence within 6 months after first remission.

    ii. Primary refractory disease which cannnot achieve complete remission (CR) after 2 cycles of standardized chemotherapy regimen.

    iii. Failure to achieve CR or relapse after one line or multiple lines of salvage chemotherapy.

    iv. Not suitable for hematopoietic stem cell transplantation (HSCT), or abandon HSCT due to various restrictions, or relapse after HSCT.

    B.Refractory/relapsed B-cell lymphoma (Meeting 1 of the first 4 items plus item 5)

    i. Tumor shrinkage less than 50% or disease progression after 4 cycles of standard chemotherapy.

    ii. Achieved CR after standard chemotherapy, but relapsed within 6 months.

    iii. 2 or more relapses after CR.

    iv. Not suitable for HSCT, or abandon HSCT due to various restrictions, or relapse after HSCT.

    v. Subjects must have received adequate treatment in the past, including anti-CD20 monoclonal antibody and combination chemotherapy with anthracyclines.

  4. B-cell malignancies include the following three types

    A. B-cell acute lymphoblastic leukemia (B-ALL)

    B. Indolent B-cell lymphoma (CLL, FL, MZL, LPL, HCL)

    C. Invasive B-cell lymphoma (DLBCL, BL, MCL)

  5. Having a measurable or evaluable lesion

    A. Patients with lymphoma require a single lesion≥15mm or 2 or more lesions≥10mm.

    B. Patients with leukemia require persistent positive or positive relapse of bone marrow MRD.

  6. Patient's main organs functioning well

    A. Liver function: ALT/AST < 3 times the upper limit of normal (ULN) and total bilirubin≤34.2μmol/L

    B. Renal function: Creatinine < 220μmol/L.

    C. Pulmonary function: Indoor oxygen saturation≥95%.

    D. Cardiac Function: Left ventricular ejection fraction (LVEF) ≥40%.

  7. The patients did not receive any antitumor treatments such as chemotherapy, radiotherapy and immunotherapy (such as immunosuppressive drugs) within 4 weeks before enrollment, and the toxicity related to previous treatments had returned to < 1 level at enrollment (except for low grade toxicity such as alopecia).
  8. The patient's peripheral superficial venous blood flow smoothly, which can meet the needs of intravenous drip.
  9. Patient ECOG score≤ 2, estimated survival time≥3 months.

Exclusion Criteria:

  1. Have a history of epilepsy or other central nervous system diseases.
  2. Women who are pregnant (urine/blood pregnancy test positive) or lactating.
  3. Male or female with a pregnancy plan in the next 1 year.
  4. Patients cannot guarantee effective contraception (condom or contraceptives, etc.) within 1 year after enrollment.
  5. Uncontrolled infectious disease within 4 weeks prior to enrollment.
  6. Active hepatitis B/C virus infection.
  7. HIV infected patients.
  8. Suffering from a serious autoimmune disease or immunodeficiency disease.
  9. The patient is allergic to macromolecular biopharmaceuticals such as antibodies or cytokines.
  10. The patient participated in other clinical trials within 6 weeks prior to enrollment.
  11. Systemic use of corticosteroids within 4 weeks prior to enrollment (except for patients with inhaled corticosteroids).
  12. Suffering from mental diseases.
  13. Patient has drug abuse/addiction.
  14. According to the researcher's judgment, the patient has other unsuitable enrollment conditions.

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: Third generation CAR-T cells
Patients receive CD22 CAR-T cells transduced with a lentiviral vector on day 0 in the absence of disease progression or unacceptable toxicity.
Patients receive CD22 CAR-T cells transduced with a lentiviral vector on day 0 in the absence of disease progression or unacceptable toxicity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants with adverse events
Time Frame: 3 years
Therapy-related adverse events were recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0).
3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
One-month remission rate
Time Frame: 1 month
Response of B-ALL to CAR-T therapy was assessed on day 30 (±2), against the National Comprehensive Cancer Network (NCCN, Version 1.2015).
1 month
Overall survival
Time Frame: 3 years
OS was calculated from the first CAR-T cell infusion to death or last follow-up (censored).
3 years
Event-free survival
Time Frame: 3 years
EFS was calculated from the first CAR-T cell infusion to death, progression of the disease, relapse or gene recurrence, whichever came first, or last visit (censored).
3 years
Relapse-free survival
Time Frame: 3 years
RFS was calculated from the first CAR-T cell infusion to relapse or last visit (censored).
3 years
Rate of anti-CD22 CAR-T cells in bone marrow cells and peripheral blood cells
Time Frame: 3 years
In vivo (bone marrow and peripheral blood) rate of CAR-T cells were determined by means of flow cytometry.
3 years
Quantity of anti-CD22 CAR-T cells in bone marrow cells and peripheral blood cells
Time Frame: 3 years
In vivo (bone marrow and peripheral blood) quantity of CAR-T cells were determined by means of flow cytometry.
3 years
Quantity of anti-CD22 CAR copies in bone marrow cells and peripheral blood cells
Time Frame: 3 years
In vivo (bone marrow and peripheral blood) quantity of anti-CD22 CAR copies were determined by means of qPCR.
3 years

Collaborators and Investigators

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

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)

August 5, 2019

Primary Completion (ANTICIPATED)

June 30, 2022

Study Completion (ANTICIPATED)

December 30, 2022

Study Registration Dates

First Submitted

June 28, 2019

First Submitted That Met QC Criteria

July 2, 2019

First Posted (ACTUAL)

July 5, 2019

Study Record Updates

Last Update Posted (ACTUAL)

August 7, 2019

Last Update Submitted That Met QC Criteria

August 5, 2019

Last Verified

August 1, 2019

More Information

Terms related to this study

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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