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

NCT ID: NCT03208556

Last Updated: 2017-09-14

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-06-21
• Study Completion Date: 2020-06-01

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.

Conditions

Relapsed or Refractory B-cell Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

iPD1 CD19 eCAR T cells

patients will receive a lymphodepletion chemotherapy prior to CAR T cell infusion

Group Type: EXPERIMENTAL

iPD1 CD19 eCAR T cells

Intervention Type: 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

Fludarabine and cyclophosphamide

Intervention Type: 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

Interventions

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

Intervention Type: BIOLOGICAL

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

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Marino Biotechnology Co., Ltd.

INDUSTRY

Sponsor Role: collaborator

Peking University

OTHER

Sponsor Role: lead

Responsible Party

Jun Zhu

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jun Zhu, MD

Role: PRINCIPAL_INVESTIGATOR

Peking University Cancer Hospital & Institute

Zhitao Ying, MD

Role: STUDY_DIRECTOR

Peking University Cancer Hospital & Institute

Xiaoyu Xiang, PhD

Role: STUDY_DIRECTOR

Marino Biotechnology Co., Ltd.

Locations

Beijing Cancer Hosptical

Beijing, , China

Site Status: RECRUITING

Countries

China

Central Contacts

Jun Zhu, MD

Role: CONTACT

zj@bjcancer.org

+86-10-88196596

Zhitao Ying, MD

Role: CONTACT

yingzhitao001@163.com

Facility Contacts

Zhitao Ying, MD

Role: primary

yingzhitao001@163.com

Other Identifiers

2017YJZ13

Identifier Type: -

Identifier Source: org_study_id