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The overall purpose of this study is to explore the therapeutic effect of CD22-targeted chimeric antigen receptor T(CAR-T) cells in the treatment of Malignant B-cell Derived Leukemia and Lymphoma.
CD22 is a type I transmembrane protein expressed on most mature B lymphocyte in the B cell malignancies,and plays a significant role in signal transduction pathways.Despite of the fact that CD19-targeted CAR-T can re-induce remissions for many patients with relapsed and refractory B cell malignancies, a part of those patients will relapse with CD19-negative malignancies. To explore a rescue for those with CD19-negative B cell malignancies, we design and conduct this trial to test the safety and effectiveness of CD22-targeted CAR-T.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| B Cell Malignancies | Experimental | Experimental: B Cell Malignancies The trial will be conducted in a manner of simon two-stage design with Anti-CD22-CAR-transduced T cells, beginning in the first stage with the aim of over 30% reaction rate among 15 patients with B cell malignancies. Only when the expected reaction rate is achieved the 30 patients left can be recruited. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Anti-CD22-CAR-transduced T cells | Biological | The first 3 enrolled patients will receive autologous-derived CD22-targeted CAR-T cells on day 1, 2 and 3 with respective 10%, 30% and 60% of the total expected dosage after receiving lymphodepleting chemotherapy. If the 3 patients don't display severe toxicity, the next patients enrolled will get infused in 2 days with respective 40% and 60% total dosage. |
| Measure | Description | Time Frame |
|---|---|---|
| Adverse Events That Are Related to Treatment | Determine the toxicity profile of the CD22 targeted CAR T cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0. | 3 years |
| Measure | Description | Time Frame |
|---|---|---|
| In vivo existence of Anti-CD22 CAR-T cells | 3 years | |
| Reaction Rate of Treatment | 3 years |
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Inclusion Criteria:
CD22-expressing B cell malignancy must be assured and must be relapsed or refractory disease. According to current traditional therapies, there must be no available alternative curative therapies and subjects must be either ineligible for allogeneic stem cell transplant (SCT), have refused SCT, or have disease activity that prohibits SCT at this time.
Patients enrolled must have an evaluated score above 60 with KPS.
CD22 expression of the malignant cells must be detected by immunohistochemistry or by flow cytometry. In general immunohistochemistry will be used for lymph node biopsies, flow cytometry will be used for peripheral blood and bone marrow samples.
Gender is not limited, age from 14 years to 75 years.
Patients must have measurable or evaluable disease at the time of enrollment, which may include any evidence of disease including minimal residual disease detected by flow cytometry, cytogenetics, or polymerase chain reaction (PCR) analysis.
Patients are expected to survive for more than 3 months by their physicians at the time of enrollment.
Adequate absolute CD3 count estimated need to be assured for obtaining target cell dose based on dosage cohorts.
Subjects with the following CNS status are eligible only in the absence of neurologic symptoms suggestive of CNS leukemia, such as cranial nerve palsy:
CNS 1, defined as absence of blasts in cerebral spinal fluid (CSF) on cytospin preparation, regardless of the number of WBCs; CNS 2, defined as presence of < 5/uL WBCs in CSF and cytospin positive for blasts, or > 5/uL WBCs but negative by Steinherz/Bleyer algorithm CNS3 with marrow disease who has failed salvage systemic and intensive IT chemotherapy (and therefore not eligible for radiation)
Ability to give informed consent.
Cardiac function: Left ventricular ejection fraction greater than or equal to 40% by MUGA or cardiac MRI, or fractional shortening greater than or equal to 28% by ECHO or left ventricular ejection fraction greater than or equal to 50% by ECHO.
Renal function: Creatinine level of peripheral blood is required no greater than 133umol/L.
Females of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects on the fetus.
Patients with history of allogeneic stem cell transplantation are eligible if there is no evidence of active GVHD and no longer taking immunosuppressive agents for at least 30 days prior to enrollment.
Patients volunteer to participate in the research.
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Cheng Qian, MD, PhD | Contact | 0086-023-68765461 | cqian3184@163.com | |
| Zhi Yang, PhD | Contact | 0086-13206140093 | Lystch@qq.com |
| Name | Affiliation | Role |
|---|---|---|
| Cheng Qian, MD, PhD | Biotherapy Center of Southwest Hospital | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Southwest Hospital of Third Millitary Medical University | Recruiting | Chongqing | Chongqing Municipality | 400000 | China |
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| ID | Term |
|---|---|
| D007938 | Leukemia |
| D008223 | Lymphoma |
| ID | Term |
|---|---|
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |