Back to results

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

Primary Purpose

Relapsed or Refractory B-cell Lymphoma

Status

Unknown status

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

iPD1 CD19 eCAR T cells

Fludarabine and cyclophosphamide

About this trial

This is an interventional treatment trial for Relapsed or Refractory B-cell Lymphoma

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

CD19+ B cell lymphoma,verified by IHC or flow cytometry.
a prior history of at least one standard care of medication.
ineligible for allogeneic transplantation or relapsed after transplantation.
patients are 18 years older.
life expectancy > 3months.
ECOG ≤ 2.
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 .
Blood: Hgb ≥ 80 g/L, ANC ≥ 1×10^9/L, PLT ≥ 50×10^9/L.
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.
measurable tumors.

Exclusion Criteria:

using immunosuppressive drugs or systemic steroids within one week of enrollment.
active infection.
HIV positive.
active hepatitis B virus infection or hepatitis C virus infection.
breastfeeding or pregnant women.
patients refuse to practice birth control during study and one year post study.
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.
currently enrolled in other study.
patients, in the opinion of investigators, may not be eligible or are not able to comply with the study.

Sites / Locations

Beijing Cancer HospticalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

iPD1 CD19 eCAR T cells

Arm Description

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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).

overall survival

Overall survival is defined as the time from receiving iPD1 CD19 eCAR T cells infusion to death for any cause.

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.

Full Information

NCT ID

NCT03208556

First Posted

June 27, 2017

Last Updated

September 12, 2017

Sponsor

Peking University

Collaborators

Marino Biotechnology Co., Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT03208556

Brief Title

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

2. Study Status

Record Verification Date

July 2017

Overall Recruitment Status

Unknown status

Study Start Date

June 21, 2017 (Actual)

Primary Completion Date

June 1, 2019 (Anticipated)

Study Completion Date

June 1, 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Peking University

Collaborators

Marino Biotechnology Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Relapsed or Refractory B-cell Lymphoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

iPD1 CD19 eCAR T cells

Arm Type

Experimental

Arm Description

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

Intervention Type

Biological

Intervention Name(s)

iPD1 CD19 eCAR T cells

Intervention Description

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

Drug

Intervention Name(s)

Fludarabine and cyclophosphamide

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Description

incidents of treatment related adverse events per NCI CTCAE V4.0

Time Frame

2 years

Secondary Outcome Measure Information:

Title

treatment response

Description

Time Frame

6 months

Title

overall survival

Description

Overall survival is defined as the time from receiving iPD1 CD19 eCAR T cells infusion to death for any cause.

Time Frame

3 years

Title

progression-free survival

Description

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.

Time Frame

2 years

Other Pre-specified Outcome Measures:

Title

Persistence of iPD1 CD19 eCAR T cells in patients

Description

measured by quantitative PCR

Time Frame

2 years

Title

proliferation of iPD1 CD19 eCAR T cells in patients

Description

measured by flow cytometry

Time Frame

6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: CD19+ B cell lymphoma,verified by IHC or flow cytometry. a prior history of at least one standard care of medication. ineligible for allogeneic transplantation or relapsed after transplantation. patients are 18 years older. life expectancy > 3months. ECOG ≤ 2. 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 . Blood: Hgb ≥ 80 g/L, ANC ≥ 1×10^9/L, PLT ≥ 50×10^9/L. 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. measurable tumors. Exclusion Criteria: using immunosuppressive drugs or systemic steroids within one week of enrollment. active infection. HIV positive. active hepatitis B virus infection or hepatitis C virus infection. breastfeeding or pregnant women. patients refuse to practice birth control during study and one year post study. 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. currently enrolled in other study. patients, in the opinion of investigators, may not be eligible or are not able to comply with the study.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Jun Zhu, MD

Phone

+86-10-88196596

zj@bjcancer.org

First Name & Middle Initial & Last Name or Official Title & Degree

Zhitao Ying, MD

yingzhitao001@163.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jun Zhu, MD

Organizational Affiliation

Peking University Cancer Hospital & Institute

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Zhitao Ying, MD

Organizational Affiliation

Peking University Cancer Hospital & Institute

Official's Role

Study Director

First Name & Middle Initial & Last Name & Degree

Xiaoyu Xiang, PhD

Organizational Affiliation

Marino Biotechnology Co., Ltd.

Official's Role

Study Director

Facility Information:

Facility Name

Beijing Cancer Hosptical

City

Beijing

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Zhitao Ying, MD

yingzhitao001@163.com

First Name & Middle Initial & Last Name & Degree

Jun Zhu, MD

First Name & Middle Initial & Last Name & Degree

Zhitao Ying, MD

First Name & Middle Initial & Last Name & Degree

Xiaoyu Xiang, PhD

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs