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| Name | Class |
|---|---|
| Marino Biotechnology Co., Ltd. | INDUSTRY |
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PD1 pathway is critical in determining the response to CAR T cell therapy. Emerging data suggested that Inhibition of PD1 could enhance the efficacy of CAR T cell therapy. iPD1 CD19 eCAR T cells is an enhanced version of the classical 2nd generation anti-CD19 4-1BB-costimulatory chimeric antigen receptor engineered T cells with cell-intrinsic PD1 inhibition by incorporation of a PD1 shRNA-expressing cassette in the CAR lentivector. This design will enhance the anti-tumor activities of CAR T cells by inhibiting PD1 induction after CAR T cell activation. This pilot, single arm, one center, dose-escalation, open label study is to determine the safety and efficacy of iPD1 CD19 eCAR T cells in relapsed or refractory CD19 positive lymphoma.
Subjects will be given a lymphodepletion chemotherapy comprised of Fludarabine and cyclophosphamide prior to CAR T cell infusion. The chemotherapy is completed 1 to 4 days before the first dost of iPD1 CD19 eCAR T cells.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| iPD1 CD19 eCAR T cells | Experimental | patients will receive a lymphodepletion chemotherapy prior to CAR T cell infusion |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| iPD1 CD19 eCAR T cells | Biological | iPD1 CD19 eCAR T cells are administrated in a 3-day split-dose regimen (d0, 30%; d1, 30%; d2, 40%). CAR T cell dose escalation: 1×10^5 /kg,1×10^6 /kg,3×10^6 /kg,and 6×10^6 CAR T cells/kg |
| Measure | Description | Time Frame |
|---|---|---|
| safety of infusion of iPD1 CD19 eCAR T cells as assessed by the incidents of treatment related adverse events per NCI CTCAE V4.0 | incidents of treatment related adverse events per NCI CTCAE V4.0 | 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| treatment response | The efficacy of infusion of iPD1 CD19 eCAR T cells is assessed according to the standardized response criteria for malignant lymphoma (Cheson BD, JCO, 2007), which is defined as complete remission (CR), partial remission (PR), stable disease (SD), or progressive disease (PD). | 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Persistence of iPD1 CD19 eCAR T cells in patients | measured by quantitative PCR | 2 years |
| proliferation of iPD1 CD19 eCAR T cells in patients | measured by flow cytometry |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Jun Zhu, MD | Contact | +86-10-88196596 | zj@bjcancer.org | |
| Zhitao Ying, MD | Contact | yingzhitao001@163.com |
| Name | Affiliation | Role |
|---|---|---|
| Jun Zhu, MD | Peking University Cancer Hospital & Institute | Principal Investigator |
| Zhitao Ying, MD | Peking University Cancer Hospital & Institute | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Beijing Cancer Hosptical | Recruiting | Beijing | China |
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| ID | Term |
|---|---|
| D012008 | Recurrence |
| D016393 | Lymphoma, B-Cell |
| ID | Term |
|---|---|
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D008228 | Lymphoma, Non-Hodgkin |
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| ID | Term |
|---|---|
| C024352 | fludarabine |
| D003520 | Cyclophosphamide |
| ID | Term |
|---|---|
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
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| Fludarabine and cyclophosphamide | Drug | Fludarabine 25 mg/m2 d1-3; cyclophosphamide 250 mg/m2 d1-3. Lymphodepletion chemotherapy is completed 1 to 4 days before CAR T cell infusion |
|
| overall survival |
Overall survival is defined as the time from receiving iPD1 CD19 eCAR T cells infusion to death for any cause. |
| 3 years |
| progression-free survival | Progression-free survival (PFS) is defined as the time from receiving iPD1 CD19 eCAR T cell infusion to disease progression or death from any cause. | 2 years |
| 6 months |
| Xiaoyu Xiang, PhD |
| Marino Biotechnology Co., Ltd. |
| Study Director |
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |