Safety and Efficacy of iPD1 CD19 eCAR T Cells in Relapsed or Refractory B-cell Lymphoma

Phase 1

• Conditions: Relapsed or Refractory B-cell Lymphoma
• Interventions: Biological: iPD1 CD19 eCAR T cells; Drug: Fludarabine and cyclophosphamide

• Registration Number: NCT03208556
• Lead Sponsor: Peking University

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2017-06-21
• Study First Submitted: 2017-06-27
• Status Verified: 2017-07
• Study First Submitted QC: 2017-07-03
• Study First Posted: 2017-07-05
• Last Update Submitted: 2017-09-12
• Last Update Posted: 2017-09-14
• Primary Completion: 2019-06-01
• Study Completion: 2020-06-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

1. CD19+ B cell lymphoma,verified by IHC or flow cytometry.
2. a prior history of at least one standard care of medication.
3. ineligible for allogeneic transplantation or relapsed after transplantation.
4. patients are 18 years older.
5. life expectancy > 3months.
6. ECOG ≤ 2.
7. satisfactory major organ functions: adequate heart function with LVEF≥50%; pulse oximetry of ≥ 90%; cockcroft-gault creatinine clearance≥40 ml/min; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3ULN; Bilirubin ≤2.0 mg/dl .
8. Blood: Hgb ≥ 80 g/L, ANC ≥ 1×10^9/L, PLT ≥ 50×10^9/L.
9. women of reproductive potential must have a negative pregnancy test. Male and female of reproductive potential must agree to use birth control during the study and one year post study.
10. measurable tumors.

Exclusion Criteria

1. using immunosuppressive drugs or systemic steroids within one week of enrollment.
2. active infection.
3. HIV positive.
4. active hepatitis B virus infection or hepatitis C virus infection.
5. breastfeeding or pregnant women.
6. patients refuse to practice birth control during study and one year post study.
7. patients with a prior history of other malignances will be excluded from this study, but patients who have been cured from skin basal cell carcinoma or cervical cancer, or who have had their tumors removed by surgical resection but without further therapies and have more than 5 years of progression-free survival, can be included into the study.
8. currently enrolled in other study.
9. patients, in the opinion of investigators, may not be eligible or are not able to comply with the study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
iPD1 CD19 eCAR T cells	iPD1 CD19 eCAR T cells	patients will receive a lymphodepletion chemotherapy prior to CAR T cell infusion
iPD1 CD19 eCAR T cells	Fludarabine and cyclophosphamide	patients will receive a lymphodepletion chemotherapy prior to CAR T cell infusion

Primary Outcome Measures

Name	Time	Method
safety of infusion of iPD1 CD19 eCAR T cells as assessed by the incidents of treatment related adverse events per NCI CTCAE V4.0	2 years	incidents of treatment related adverse events per NCI CTCAE V4.0

Secondary Outcome Measures

Name	Time	Method
treatment response	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	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	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.

Trial Locations

Locations (1)

Beijing Cancer Hosptical; 🇨🇳 Beijing, China