Clinical trial NCT03208556: Safety and Efficacy of iPD1 CD19 eCAR T Cells in Relapsed or Refractory B-cell Lymphoma
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Relapsed or Refractory B-cell Lymphoma
Lead sponsor: Peking University
Sponsor class: OTHER
Collaborators: name: Marino Biotechnology Co., Ltd.
First posted: 2017-07-05
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: safety of infusion of iPD1 CD19 eCAR T cells as assessed by the incidents of treatment related adverse events per NCI CTCAE V4.0
timeFrame: 2 years
Secondary outcomes:
measure: treatment response
timeFrame: 6 months
measure: overall survival
timeFrame: 3 years
measure: progression-free survival
timeFrame: 2 years
Other outcomes:
measure: Persistence of iPD1 CD19 eCAR T cells in patients
timeFrame: 2 years
measure: proliferation of iPD1 CD19 eCAR T cells in patients
timeFrame: 6 months
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hosptical
Study officials:
affiliation: Peking University Cancer Hospital & Institute
name: Jun Zhu, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Peking University Cancer Hospital & Institute
name: Zhitao Ying, MD
role: STUDY_DIRECTOR
affiliation: Marino Biotechnology Co., Ltd.
name: Xiaoyu Xiang, PhD
role: STUDY_DIRECTOR
References: