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

NCT ID: NCT04007978

Last Updated: 2019-08-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE1

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-08-05

Study Completion Date

2022-12-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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B Cell Lymphoma Acute Lymphoblastic Leukemia

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Third generation CAR-T cells

Intervention Type GENETIC

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

Interventions

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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.

Intervention Type GENETIC

Eligibility Criteria

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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.
Minimum Eligible Age

14 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Wuhan Bio-Raid Biotechnology Co., Ltd.

UNKNOWN

Sponsor Role collaborator

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

OTHER

Sponsor Role lead

Responsible Party

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MEI HENG

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Heng Mei, M.D., Ph.D

Role: PRINCIPAL_INVESTIGATOR

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Locations

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Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Yu Hu, M.D., Ph.D

Role: CONTACT

86-13986183871

Heng Mei, M.D., Ph.D

Role: CONTACT

86-13886160811

Facility Contacts

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Yu Hu, M.D., Ph.D

Role: primary

86-13986183871

Heng Mei, M.D., Ph.D

Role: backup

86-13886160811

Other Identifiers

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WHUH-CART-CD22-01

Identifier Type: -

Identifier Source: org_study_id

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