Safety and Efficiency Study of CD19-PD1-CART Cell in Relapsed/Refractory B Cell Lymphoma

November 14, 2019 updated by: Quanshun Wang, Chinese PLA General Hospital
This is a single center, non-randomized, open-label, phase 2 study to evaluate the efficacy and safety of CD19-PD1-CART cells therapy for patients with relapsed/refractory B Cell Lymphoma.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Lymphoma is a malignant tumor originating from lymph nodes or other lymphoid tissues. It can be divided into B cells, T cells, and NK cell lymphomas depending on the origin of different lymphocytes. Among them, B cell lymphoma accounts for about 90% of lymphoma.

Chimeric antigen receptor T (CART) cells is a promising treatment for lymphoma. T lymphocytes from patients are separated and engineered with CD19-CAR, to specifically recognize and eliminate CD19-positive tumor cells. At present, many CD19CART cells therapy studies are in the stage of clinical research and have achieved significant clinical effects.

Although there are some CD9CART cells clinical trials, the therapeutic effect on lymphoma is significantly lower than that of acute leukemia. One of the reasons is that lymphoma has the nature of solid tumors, whichi has a certain immunosuppressive microenvironment. The clinical trials of anti-PD-1 antibody drugs against lymphoma also show good therapeutic efficacy. Therefore, the combination of anti-PD-1 or PD-L1 antibody and CD19CART is one of the ways to improve the therapeutic effect of CART cells.

The investigators screened PD-1 mutants that have high bind with the PD-L1 ligand, and prepared CD19CART which secretes the mutant PD-1Fc fusion protein. Preclinical studies have shown that CD19CART cells secreting mutant PD-1Fc fusion protein have a superior killing effect to CD19CART cells which does not express PD-1 fusion protein.

The trial was conducted to explore the safety and efficacy of CD19-PD1-CART cells in Relapsed/Refractory B Cell Lymphoma.

Study Type

Interventional

Enrollment (Anticipated)

30

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Hainan
      • Sanya, Hainan, China, 572000
        • Recruiting
        • Hai Nan Hospital of Chinese PLA General Hospital
        • Contact:
        • Principal Investigator:
          • Quanshun Wang
        • Principal Investigator:
          • Lixun Guan
        • Principal Investigator:
          • Wenshuai Zheng
        • Principal Investigator:
          • Zhenyang Gu
        • Principal Investigator:
          • Lu Wang
        • Principal Investigator:
          • Yuanyuan Xu
        • Principal Investigator:
          • Yalei Hu
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 80 years (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Male or female, aged 14 to 80 years (including 14 and 80 years old).

  2. The diagnosis was Refractory/relapsed B-cell lymphoma.(Meeting 1 of the first 4 items plus item 5)

    A.Tumor shrinkage less than 50% or disease progression after 4 cycles of standard chemotherapy.

    B.Achieved CR after standard chemotherapy, but relapsed within 6 months.

    C.2 or more relapses after CR.

    D.Not suitable for HSCT, or relapse after HSCT.

    E.Subjects must have received adequate treatment in the past and the predicted survival is more than three months.

  3. Patient or his or her legal guardian voluntarily participates in this stuy and signs an informed consent form.
  4. Flow cytometry or immunohistochemistry showed CD19 positive in tumor cells.
  5. No serious concomitant disease and major organ function is not serious abnormal.
  6. ECOG physical condition score 0-3 or KPS score > 80.
  7. the test meets the following indicators:

A.ALT/AST < 2.5 times the upper limit of normal (ULN) and total bilirubin≤34.2μmol/L.

B.Creatinine < 176.8 μmol/L.

C.WBC≥2.5×109/L ，LY≥0.7×109/L，LY%≥15%.

D.PT/INR < 1.7 or PT was extended by less than 4 seconds.

Exclusion Criteria:

  1. Women who are pregnant or breastfeeding.
  2. Patients whose tumor cell don't have positive CD19 antigen.
  3. Active hepatitis B or hepatitis C, HIV/AIDS infection, any uncontrolled active infection.
  4. Patients who are using steroid drugs throughout the body currently.
  5. Patients who have received any gene therapy in the past.
  6. Patients who are allergy to immunotherapy and related drugs.
  7. Patients with heavy heart disease or poorly controlled high blood pressure.
  8. Patients who received chemotherapy or radiation 4 weeks before the study began.
  9. Patients who are participating in other clinical trials.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: CD19+ Lymphoma
This study is to evaluate the efficacy and safety of CD19-PD1-CART cells therapy for patients with Relapsed/Refractory B Cell Lymphoma.
Biological: CD19-PD1-CART Cell
This study was a single-center, open-label, single-arm, non-randomized clinical trial, which has 3 groups by infusion dose level. Firstly, each dose group has 3 patients. The pretreatment regimen of cyclophosphamide (25mg/m2 for 3 consecutive days) and fludarabine (10mg/kg for 3 consecutive days) was given before CART cells were reinfused. CART cells were reinfused on the third day after the pretreatment. If no serious side effects emerges in the group, then the next group uses the subsequent higher dose. If serious side effects emerges in a single patients in any dose level, 3 more patients will be enrolled to the same dose level. After 9 or more patients, the investigators select the safest dose and recruit more patients for CART test to explore its effectiveness.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of Treatment-related Adverse Events
Time Frame: 3 years
Therapy-related adverse events will be recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0).
3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Remission Rate(ORR) of CD19-PD1-CART cells in Lymphoma
Time Frame: 3 years
ORR will be assessed from the first CAR-T cell infusion to death or last follow-up
3 years
Overall survival(OS) of CD19-PD1-CART cells in Lymphoma
Time Frame: 3 years
OS will be assessed from the first CAR-T cell infusion to death or last follow-up
3 years
Progress-free survival(PFS) of CD19-PD1-CART cells in Lymphoma
Time Frame: 3 years
PFS will be assessed from the first CAR-T cell infusion to death or last follow-up
3 years
Rate of CD19-PD1-CARTcells in peripheral blood cells
Time Frame: 3 years
In vivo (peripheral blood) rate of CD19-PD1-CART cells were determined by means of flow cytometry.
3 years
Quantity of CD19-PD1-CART cells copies in peripheral blood cells.
Time Frame: 3 years
In vivo (peripheral blood) quantity of CD19-PD1-CART cells copies copies were determined by means of qPCR.
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Chinese PLA General Hospital

Investigators

  • Study Chair: Quanshun Wang, Hainan hospital of Chinese PLA General Hospital
  • Principal Investigator: Lu Wang, Hainan hospital of Chinese PLA General Hospital
  • Principal Investigator: Yuanyuan Xu, Hainan hospital of Chinese PLA General Hospital
  • Study Director: Wengshuai Zheng, Hainan hospital of Chinese PLA General Hospital
  • Principal Investigator: Lixun Guan, Hainan hospital of Chinese PLA General Hospital
  • Principal Investigator: Yalei Hu, Hainan hospital of Chinese PLA General Hospital
  • Principal Investigator: Zhengyang Gu, Hainan hospital of Chinese PLA General Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

July 7, 2019

Primary Completion (ANTICIPATED)

July 1, 2021

Study Completion (ANTICIPATED)

July 1, 2022

Study Registration Dates

First Submitted

November 12, 2019

First Submitted That Met QC Criteria

November 12, 2019

First Posted (ACTUAL)

November 14, 2019

Study Record Updates

Last Update Posted (ACTUAL)

November 15, 2019

Last Update Submitted That Met QC Criteria

November 14, 2019

Last Verified

November 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HNYY-XYK-02

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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