Clinical trial NCT02349698: A Clinical Research of CAR T Cells Targeting CD19 Positive Malignant B-cell Derived Leukemia and Lymphoma
Official title: A Clinical Research of Chimeric Antigen Receptor (CAR) T Cells Targeting CD19 Positive Malignant B-cell Derived Leukemia and Lymphoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Leukemia
Lymphoma
Keywords: CAR T
Leukemia
Lymphoma
Lead sponsor: Southwest Hospital, China
Sponsor class: OTHER
First posted: 2015-01-29
Enrollment: 45
Sex: ALL
Minimum age (years): 4
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The main purpose of this research is to verify the safety of CD19 targeted chimeric antigen receptor T cells and to determine the proper dosage of CAR T cells infused.

Detailed description: Nowadays refractory or relapsed leukemia/lymphoma lacks effective treatment. Innovative therapy is urgently required. Chimeric antigen receptor (CAR)-modified T cells have demonstrated great successes in treating even late stage cluster of differentiation antigen 19 (CD19) positive B cell malignancies. To design better CAR T cells, we have developed new CD19 CARs. Preclinical studies have demonstrated effective killing of CD19 target cells. In this study, the CD19 CARs, will be evaluated in CD19 positive leukemia/lymphoma patients. The primary goal is to confirm its adverse effects including cytokine storm response and any other adverse effects. In addition, tumor targeting and disease status after treatment will also be evaluated.

Eligibility criteria: Inclusion Criteria:

1. Relapsed or refractory B cell derived acute lymphoblastic leukemia(ALL), chronic lymphocytic leukemia(CLL) and non-hodgkin lymphoma.
2. KPS\>60.
3. Life expectancy\>3 months.
4. Gender unlimited, age from 4 years to 75 years.
5. Disease progresses but reserves reaction to recent treatments.
6. Patients who have failed at least one line of a standard treatment.
7. No serious mental disorder.
8. Patients must have adequate cardiac function(no cardiac disease, LVEF≥40% ), adequate pulmonary function as indicated by room air oxygen saturation of \>94%, and adequate renal function(Cr≤133umol/L).
9. No other serious diseases(autoimmune disease, immunodeficiency etc.).
10. No other tumors.
11. Patients volunteer to participate in the research.

Exclusion Criteria:

1. HIV affected.
2. Patients are allergic to cytokines.
3. Central nervous system leukemia within 28 days.
4. Uncontrolled active infection.
5. Acute or chronic GVHD.
6. Treated with T cell inhibitor.
7. Pregnancy and nursing females.
8. Other situations we think improper for the research.

Primary outcomes:
measure: Adverse events of each patient.
timeFrame: 3 years
Secondary outcomes:
measure: Survival time of Anti-CD19 CAR T cells in vivo.
timeFrame: 3 years
measure: Efficacy of anti-CD19 CAR T cells assessed by the ability of CAR T cells to kill leukemia/lymphoma cells
timeFrame: 12 weeks
measure: Maximum tolerated dose (MTD) of CD19 targeted CAR T cells.
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Chongqing
country: China
facility: Southwest Hospital of Third Millitary Medical University
state: Chongqing
Study officials:
affiliation: Biotherapy Center of Southwest Hospital
name: Cheng Qian, MD, PhD
role: STUDY_CHAIR
References:
citation: Htun KT, Gong Q, Ma L, Wang P, Tan Y, Wu G, Chen J. Successful Treatment of Refractory and Relapsed CNS Acute Lymphoblastic Leukemia With CD-19 CAR-T Immunotherapy: A Case Report. Front Oncol. 2021 Aug 26;11:699946. doi: 10.3389/fonc.2021.699946. eCollection 2021.
citation: Heng G, Jia J, Li S, Fu G, Wang M, Qin D, Li Y, Pei L, Tian X, Zhang J, Wu Y, Xiang S, Wan J, Zhu W, Zhang P, Zhang Q, Peng X, Wang L, Wang P, Wei Z, Zhang Y, Wang G, Chen X, Zhang C, Sun Y, Zhao W, Fan Y, Yang Z, Chen J, Qian C. Sustained Therapeutic Efficacy of Humanized Anti-CD19 Chimeric Antigen Receptor T Cells in Relapsed/Refractory Acute Lymphoblastic Leukemia. Clin Cancer Res. 2020 Apr 1;26(7):1606-1615. doi: 10.1158/1078-0432.CCR-19-1339. Epub 2019 Nov 15.