- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04007978
Anti-CD22 Chimeric Antigen Receptor (CAR)-Modified T Cell Therapy for Relapsed Refractory B-cell Malignancies
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
Study Overview
Status
Conditions
Intervention / Treatment
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
Enrollment (Anticipated)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Hubei
-
Wuhan, Hubei, China, 430022
- Recruiting
- Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Patient or his or her legal guardian voluntarily participates in and signs an informed consent form.
- Male or female patients aged 14 to 70 years (including 14 and 70 years old).
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.
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)
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.
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%.
- 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).
- The patient's peripheral superficial venous blood flow smoothly, which can meet the needs of intravenous drip.
- Patient ECOG score≤ 2, estimated survival time≥3 months.
Exclusion Criteria:
- Have a history of epilepsy or other central nervous system diseases.
- Women who are pregnant (urine/blood pregnancy test positive) or lactating.
- Male or female with a pregnancy plan in the next 1 year.
- Patients cannot guarantee effective contraception (condom or contraceptives, etc.) within 1 year after enrollment.
- Uncontrolled infectious disease within 4 weeks prior to enrollment.
- Active hepatitis B/C virus infection.
- HIV infected patients.
- Suffering from a serious autoimmune disease or immunodeficiency disease.
- The patient is allergic to macromolecular biopharmaceuticals such as antibodies or cytokines.
- The patient participated in other clinical trials within 6 weeks prior to enrollment.
- Systemic use of corticosteroids within 4 weeks prior to enrollment (except for patients with inhaled corticosteroids).
- Suffering from mental diseases.
- Patient has drug abuse/addiction.
- According to the researcher's judgment, the patient has other unsuitable enrollment conditions.
Study Plan
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
Sponsor
Collaborators
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ANTICIPATED)
Study Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- WHUH-CART-CD22-01
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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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