Anti-CD22 Chimeric Antigen Receptor (CAR)-Modified T Cell Therapy for Relapsed Refractory B-cell Malignancies
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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 Design
Arms and Interventions
| 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. |
Genetic: 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.
|
Outcome Measures
Primary Outcome Measures
- Number of participants with adverse events [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).
Secondary Outcome Measures
- One-month remission rate [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).
- Overall survival [3 years]
OS was calculated from the first CAR-T cell infusion to death or last follow-up (censored).
- Event-free survival [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).
- Relapse-free survival [3 years]
RFS was calculated from the first CAR-T cell infusion to relapse or last visit (censored).
- Rate of anti-CD22 CAR-T cells in bone marrow cells and peripheral blood cells [3 years]
In vivo (bone marrow and peripheral blood) rate of CAR-T cells were determined by means of flow cytometry.
- Quantity of anti-CD22 CAR-T cells in bone marrow cells and peripheral blood cells [3 years]
In vivo (bone marrow and peripheral blood) quantity of CAR-T cells were determined by means of flow cytometry.
- Quantity of anti-CD22 CAR copies in bone marrow cells and peripheral blood cells [3 years]
In vivo (bone marrow and peripheral blood) quantity of anti-CD22 CAR copies were determined by means of qPCR.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Patient or his or her legal guardian voluntarily participates in and signs an informed consent form.
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Male or female patients aged 14 to 70 years (including 14 and 70 years old).
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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)
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Recurrence within 6 months after first remission.
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Primary refractory disease which cannnot achieve complete remission (CR) after 2 cycles of standardized chemotherapy regimen.
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Failure to achieve CR or relapse after one line or multiple lines of salvage chemotherapy.
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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)
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Tumor shrinkage less than 50% or disease progression after 4 cycles of standard chemotherapy.
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Achieved CR after standard chemotherapy, but relapsed within 6 months.
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2 or more relapses after CR.
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Not suitable for HSCT, or abandon HSCT due to various restrictions, or relapse after HSCT.
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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
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B-cell acute lymphoblastic leukemia (B-ALL)
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Indolent B-cell lymphoma (CLL, FL, MZL, LPL, HCL)
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Invasive B-cell lymphoma (DLBCL, BL, MCL)
- Having a measurable or evaluable lesion
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Patients with lymphoma require a single lesion≥15mm or 2 or more lesions≥10mm.
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Patients with leukemia require persistent positive or positive relapse of bone marrow MRD.
- Patient's main organs functioning well
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Liver function: ALT/AST < 3 times the upper limit of normal (ULN) and total bilirubin≤34.2μmol/L
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Renal function: Creatinine < 220μmol/L.
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Pulmonary function: Indoor oxygen saturation≥95%.
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Cardiac Function: Left ventricular ejection fraction (LVEF) ≥40%.
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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).
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The patient's peripheral superficial venous blood flow smoothly, which can meet the needs of intravenous drip.
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Patient ECOG score≤ 2, estimated survival time≥3 months.
Exclusion Criteria:
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Have a history of epilepsy or other central nervous system diseases.
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Women who are pregnant (urine/blood pregnancy test positive) or lactating.
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Male or female with a pregnancy plan in the next 1 year.
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Patients cannot guarantee effective contraception (condom or contraceptives, etc.) within 1 year after enrollment.
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Uncontrolled infectious disease within 4 weeks prior to enrollment.
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Active hepatitis B/C virus infection.
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HIV infected patients.
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Suffering from a serious autoimmune disease or immunodeficiency disease.
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The patient is allergic to macromolecular biopharmaceuticals such as antibodies or cytokines.
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The patient participated in other clinical trials within 6 weeks prior to enrollment.
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Systemic use of corticosteroids within 4 weeks prior to enrollment (except for patients with inhaled corticosteroids).
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Suffering from mental diseases.
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Patient has drug abuse/addiction.
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According to the researcher's judgment, the patient has other unsuitable enrollment conditions.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Union Hospital, Tongji Medical College, Huazhong University of Science and Technology | Wuhan | Hubei | China | 430022 |
Sponsors and Collaborators
- Wuhan Union Hospital, China
- Wuhan Bio-Raid Biotechnology Co., Ltd.
Investigators
- Principal Investigator: Heng Mei, M.D., Ph.D, Wuhan Union Hospital, China
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- WHUH-CART-CD22-01