CD19-directed CAR T Cells Therapy in Relapsed/Refractory B Cell Malignancy

Phase 1

• Conditions: Leukemia; Lymphoma
• Interventions: Biological: CD19-directed CAR-T cells

• Registration Number: NCT02537977
• Lead Sponsor: Shanghai Tongji Hospital, Tongji University School of Medicine

Brief Summary

Relapsed/refractory leukemia and lymphoma lack effective treatment. The cancer immunotherapy with chimeric antigen receptor (CAR) T cells provides a potent new approach for them. In this clinical trial, the investigators aim to assess the safety and efficacy of administering T cell expressing an anti-CD19 CARs to patients with chemotherapy resistant or refractory CD19 positive B cell malignancy including leukemia and lymphoma.

Detailed Description

Tongji Hospital of Tongji University has developed an investigational approach for treating patients with CD19 positive B cell malignancy that involves taking white blood cells from the patient, growing them in the laboratory in large numbers, genetically modifying these specific cells with lentivirus to attack CD19 positive cells, and then giving the cells back to the patients.The main purpose of the study is to assess the safety and efficacy of the treatment with anti-CD19 CAR-T cells in the patients with chemotherapy resistant or refractory CD19 positive B cell malignancy including leukemia and lymphoma.

Study Timeline

• Study Start: 2015-07
• Study First Submitted: 2015-08-26
• Study First Submitted QC: 2015-08-28
• Study First Posted: 2015-09-02
• Status Verified: 2018-11
• Last Update Submitted: 2018-11-29
• Last Update Posted: 2018-12-03
• Primary Completion: 2020-06
• Study Completion: 2020-06

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

• Patients with CD19+ leukemia or lymphoma, meeting the following criteria:

  • At least 2 prior combination chemotherapy regimens (not including single agent monoclonal antibody (Rituximab) therapy)
  • Less than 1 year between last chemotherapy and progression
  • Not eligible or appropriate for allo-HSCT

• To be aged 6 to 85 years

• Estimated survival of ≥ 6 months, but ≤ 2 years

• ECOG score ≤2

• Relapse after auto-HSCT

• Women of childbearing potential must have a urine pregnancy test taken and proven negative prior to the treatment. All patients agree to use reliable methods of contraception during the trial period and until follow-up for the last time

• Voluntary participation in the clinical trials and sign the informed consent

Exclusion Criteria

• History of epilepsy or other CNS disease
• Patients have GVHD, which needs treatment with immunosuppressive agents
• Patients with prolonged QT interval or severe heart disease
• Patients in pregnancy or breast-feeding period
• Uncontrolled active infection
• Active hepatitis B or hepatitis C infection
• Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary
• Previously treatment with any gene therapy products
• Feasibility assessment during screening demonstrates <20% transduction of target lymphocytes, or insufficient expansion (<5-fold) in response to CD3/CD28 costimulation
• ALT /AST>3 x normal value; Creatinine> 2.5 mg/dl; Bilirubin >2.0 mg/dl
• Any uncontrolled medical disorders that the researchers consider are not eligible to participate the clinical trial
• HIV infection
• Any situation that would increase dangerousness of subjects or disturb the outcome of the clinical study according to the researcher's evaluation

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CAR-T cells	CD19-directed CAR-T cells	Autologous 2nd generation CD19-directed CAR-T cells

Primary Outcome Measures

Name	Time	Method
Occurrence of study related adverse events	2 years	defined as \>= Grade 3 signs/symptoms, laboratory toxicities, and clinical events) that are possibly，likely，or definitely related to the study.

Secondary Outcome Measures

Name	Time	Method
Response rates to CAR-T cells	2 years	Describe the response rates of patients treated with CAR-T cells, including complete remission, partial remission,stable disease and progression disease
Overall survival(OS) of patients treated with CAR-T cells	2 years
Progression free survival(PFS)	2 years
Duration of remission(DOR)	2 years

Trial Locations

Locations (1)

Shanghai Tongji Hospital, Tongji University School of Medicine; 🇨🇳 Shanghai, China