Safety and Efficacy of iPD1 CD19 eCAR T Cells in Relapsed or Refractory B-cell Lymphoma
|ClinicalTrials.gov Identifier: NCT03208556|
Recruitment Status : Unknown
Verified July 2017 by Jun Zhu, Peking University.
Recruitment status was: Recruiting
First Posted : July 5, 2017
Last Update Posted : September 14, 2017
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.
|Condition or disease||Intervention/treatment||Phase|
|Relapsed or Refractory B-cell Lymphoma||Biological: iPD1 CD19 eCAR T cells Drug: Fludarabine and cyclophosphamide||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Pilot Study of Autologous Anti-CD19 4-1BB CAR T Cells With Cell-intrinsic PD1 Inhibition in Relapsed or Refractory B-cell Lymphoma|
|Actual Study Start Date :||June 21, 2017|
|Estimated Primary Completion Date :||June 1, 2019|
|Estimated Study Completion Date :||June 1, 2020|
Experimental: iPD1 CD19 eCAR T cells
patients will receive a lymphodepletion chemotherapy prior to CAR T cell infusion
Biological: iPD1 CD19 eCAR T cells
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
Drug: Fludarabine and cyclophosphamide
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
- safety of infusion of iPD1 CD19 eCAR T cells as assessed by the incidents of treatment related adverse events per NCI CTCAE V4.0 [ Time Frame: 2 years ]incidents of treatment related adverse events per NCI CTCAE V4.0
- treatment response [ Time Frame: 6 months ]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).
- overall survival [ Time Frame: 3 years ]Overall survival is defined as the time from receiving iPD1 CD19 eCAR T cells infusion to death for any cause.
- progression-free survival [ Time Frame: 2 years ]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.
- Persistence of iPD1 CD19 eCAR T cells in patients [ Time Frame: 2 years ]measured by quantitative PCR
- proliferation of iPD1 CD19 eCAR T cells in patients [ Time Frame: 6 months ]measured by flow cytometry
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03208556
|Contact: Jun Zhu, MDfirstname.lastname@example.org|
|Contact: Zhitao Ying, MDemail@example.com|
|Beijing Cancer Hosptical||Recruiting|
|Contact: Zhitao Ying, MD firstname.lastname@example.org|
|Principal Investigator: Jun Zhu, MD|
|Sub-Investigator: Zhitao Ying, MD|
|Sub-Investigator: Xiaoyu Xiang, PhD|
|Principal Investigator:||Jun Zhu, MD||Beijing Cancer Hospital|
|Study Director:||Zhitao Ying, MD||Beijing Cancer Hospital|
|Study Director:||Xiaoyu Xiang, PhD||Marino Biotechnology Co., Ltd.|