Clinical trial NCT02537977: CD19-directed CAR T Cells Therapy in Relapsed/Refractory B Cell Malignancy
Official title: CD19-directed Chimeric Antigen Receptor T Cells Therapy in Relapsed/Refractory B Cell Malignancy
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Leukemia
Lymphoma
Lead sponsor: Shanghai Tongji Hospital, Tongji University School of Medicine
Sponsor class: OTHER
First posted: 2015-09-02
Enrollment: 60
Sex: ALL
Minimum age (years): 6
Maximum age (years): 85
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Occurrence of study related adverse events
timeFrame: 2 years
Secondary outcomes:
measure: Response rates to CAR-T cells
timeFrame: 2 years
measure: Progression free survival(PFS)
timeFrame: 2 years
measure: Duration of remission(DOR)
timeFrame: 2 years
measure: Overall survival(OS) of patients treated with CAR-T cells
timeFrame: 2 years
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Tongji Hospital, Tongji University School of Medicine
Study officials:
affiliation: Shanghai Tongji Hospital, Tongji University School of Medicine
name: Aibin Liang, MD,Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: