Autologous CD19 CAR T Cells in Relapsed or Refractory B-cell Lymphoma

A Safety and Efficacy Study of Autologous T Cells Engineered to Express Chimeric Antigen Receptor Targeting CD19 in Patients With Relapsed or Refractory B-cell Lymphoma

This is a single arm, open-label, one center, dose escalation clinical study to determine the safety and efficacy of infusion of autologous T cells expressing CD19-redirected Chimeric Antigen Receptor (CD19 CAR T) in adult patients with relapsed or refractory CD19 positive B-cell lymphoma.

Study Overview

• Status: Unknown
• Conditions: B-cell Lymphoma
• Intervention / Treatment: Biological: autologous anti-CD19 CAR T cells

• Study Type: Interventional
• Enrollment (Anticipated): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100142
    • Peking university cancer hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. CD19+ B cell lymphoma,verified by IHC or flow cytometry.
2. a prior history of at least two 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 Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: CD19 CAR T cells; A standard dose escalation approach aimed to assess the safety and efficacy of autologous anti-CD19 CAR T cells will be applied.

Biological: autologous anti-CD19 CAR T cells; Patients will receive a three-day regimen of chemotherapy consisting of fludarabine and cyclophosphamide aimed to deplete the lymphocytes. Four days after lymphodepletion, patients are intravenously infused autologous anti-CD19 CAR T cells. A prescribed CAR T cell dose will be intravenously infused to patient in a three-day split-dose regimen (day0,30%; day1, 30%; day2, 40%).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of patients with adverse events	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment response rate of anti-CD19 CAR T cell infusion	Defined as the proportion of patients who achieved complete remission (CR), partial remission (PR), stable disease (SD), or progressive disease (PD) based on standardized response criteria for malignant lymphoma (Cheson BD, JCO, 2007).	4 weeks
overall survival rate of patients treated with anti-CD19 CAR T cells		2 years
progression-free survival of patients treated with anti-CD19 CAR T cells		2 years

Other Outcome Measures

Outcome Measure	Time Frame
Persistence of CAR T cells in patients	2 years

Collaborators and Investigators

• Sponsor: Peking University
• Collaborators: Marino Biotechnology Co., Ltd.

Publications and helpful links

General Publications

• Ying Z, Huang XF, Xiang X, Liu Y, Kang X, Song Y, Guo X, Liu H, Ding N, Zhang T, Duan P, Lin Y, Zheng W, Wang X, Lin N, Tu M, Xie Y, Zhang C, Liu W, Deng L, Gao S, Ping L, Wang X, Zhou N, Zhang J, Wang Y, Lin S, Mamuti M, Yu X, Fang L, Wang S, Song H, Wang G, Jones L, Zhu J, Chen SY. A safe and potent anti-CD19 CAR T cell therapy. Nat Med. 2019 Jun;25(6):947-953. doi: 10.1038/s41591-019-0421-7. Epub 2019 Apr 22.

Study record dates

Study Major Dates

• Study Start: June 1, 2016
• Primary Completion (ACTUAL): February 28, 2018
• Study Completion (ANTICIPATED): August 1, 2019

Study Registration Dates

• First Submitted: July 13, 2016
• First Submitted That Met QC Criteria: July 19, 2016
• First Posted (ESTIMATE): July 22, 2016

Study Record Updates

• Last Update Posted (ACTUAL): February 25, 2019
• Last Update Submitted That Met QC Criteria: February 21, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell
• Other Study ID Numbers: 2016YJZ12

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES