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In the conventional treatment options, B cell leukemia could be treated with chemotherapy drugs or HSCT. But chemotherapy could barely cured leukemia. And HSCT is often limited by lacking of HLA-matched donors, even if those patients who received HSCT still could be relapsed. And now, chimeric antigen receptor modified T cell infusion maybe an effective treatment to solve these problems. The investigators use a 2nd CAR- T with the optimized hinge and transmembrane domain to treat patients with relapsed or refractory B cell leukemia, including relapsed cases after HSCT. The purpose of this study is to assess the safety and efficacy of this 2nd CAR-T cells. At the same time, evaluating the possible and clinical responses of using donor-derived T cells engineered CAR-T cells.
Detailed Description: This study is being conducted to assess anti-CD19-CAR-T cells safety and efficacy in treating patients with B cell leukemia. The investigators constructed a 2nd CAR, CD19 as target protein, 4-1BB as co-stimulator. And optimized the spatial conformation by a suitable hinge & transmembrane domain sequences. The source of T cells for CAR-T is from two aspects, one is autologous, the other is donor-derived (only suitable for patients received HSCT before and relapsed). The infusion dose is (1-5)×106 CAR positive T cells/kg, and the specific cells numbers depend on the situation of individual CAR-T cells preparation.
This study is being conducted to assess anti-CD19-CAR-T cells safety and efficacy in treating patients with B cell leukemia. The investigators constructed a 2nd CAR, using CD19 as target, using 4-1BB as co-stimulator, and optimized the spatial conformation by a suitable hinge and transmembrane domain sequences. The source of T cells used to prepare CAR-T could be either autologous, or donor-derived (only suitable for patients received HSCT before and relapsed). The infusion dose is (1-5)×106 CAR positive T cells/kg, and the specific cells numbers depends on the situation of individual CAR-T cells preparation.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| anti-CD19-CAR-T cells | Experimental | patients receive chemotherapy(CF, cyclophosphamide and Fludarabine) on day -6 to day -1, then infusied with anti-CD19-CAR-T cells transduced with lentivirus on day 0 in the absence of disease progression or unacceptable toxicity. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| anti-CD19-CAR-T cells | Drug | a 2nd CAR, CD19 as target protein, 4-1BB as co- stimulator, and optimized the spatial conformation by a suitable hinge & transmembrane domain sequences |
| Measure | Description | Time Frame |
|---|---|---|
| Number of patients with adverse event | asverse event is evaluated with CTCAE, version 4.0 | 6 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Number of patients with tumor response | summarize tumor response by overal response rates | 8 weeks |
| Detection of transferred T cells in the circulation using quantitative -PCR | 6 weeks |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Jianmin Yang, Doctor | Contact | 86-18317172636 | yangjianmin@csco.org.cn | |
| Xuejun Yu, Master | Contact | 86-18616108610 | yuxuejun@genechem.com.cn |
| Name | Affiliation | Role |
|---|---|---|
| Jianmin Yang, Doctor | Shanghai Changhai Hospital,The Second Military Medical University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Shanghai Changhai Hospital,The Second Military Medical University | Recruiting | Shanghai | Shanghai Municipality | 200090 | China |
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| ID | Term |
|---|---|
| D015448 | Leukemia, B-Cell |
| D007938 | Leukemia |
| ID | Term |
|---|---|
| D007945 | Leukemia, Lymphoid |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
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|
| D006425 |
| Hemic and Lymphatic Diseases |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |