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

• ClinicalTrials.gov Identifier: NCT02842138
• Recruitment Status: Unknown
• First Posted: July 22, 2016
• Last Update Posted: February 25, 2019
• Sponsor: Peking University
• Collaborator: Marino Biotechnology Co., Ltd.
• Information provided by (Responsible Party): Jun Zhu, Peking University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
B-cell Lymphoma	Biological: autologous anti-CD19 CAR T cells	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 25 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: June 2016
• Actual Primary Completion Date: February 28, 2018
• Estimated Study Completion Date: August 2019

Arms and Interventions

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%).

Outcome Measures

Primary Outcome Measures :

1. Number of patients with adverse events [ Time Frame: 2 years ]

Secondary Outcome Measures :

1. Treatment response rate of anti-CD19 CAR T cell infusion [ Time Frame: 4 weeks ]
   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).
2. overall survival rate of patients treated with anti-CD19 CAR T cells [ Time Frame: 2 years ]
3. progression-free survival of patients treated with anti-CD19 CAR T cells [ Time Frame: 2 years ]

Other Outcome Measures:

1. Persistence of CAR T cells in patients [ Time Frame: 2 years ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

China

Peking University Cancer Hospital

Beijing, China, 100142

Sponsors and Collaborators

Peking University

Marino Biotechnology Co., Ltd.

Investigators

• Principal Investigator: Jun Zhu, MD; Peking University Cancer Hospital & Institute

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Jun Zhu, Principal Investigator, Peking University
• ClinicalTrials.gov Identifier: NCT02842138
• Other Study ID Numbers: 2016YJZ12
• First Posted: July 22, 2016
• Last Update Posted: February 25, 2019
• Last Verified: February 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

Additional relevant MeSH terms:

Lymphoma; Lymphoma, B-Cell; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin