Immunotherapy With CD19 CART-cells for B Cell Acute Lymphoblastic Leukemia

Safety and Clinical Activity of CD19 Chimeric Antigen Receptor T Cells in Treating Patients With Recurrent or Refractory CD19 Positive B Cell Acute Lymphoblastic Leukemia

This study aims to evaluate the safety and clinical activity of CD19 Chimeric Antigen Receptor (CAR) redirected autologous T-cells in treating patients with recurrent or refractory CD19 positive B cell ccute lymphoblastic leukemia,and dynamically observe the changes of CAR-T in patients and the residual tumor.

Study Overview

• Status: Unknown
• Conditions: Leukemia, B-Cell
• Intervention / Treatment: Biological: CD19-targeted CART cells

Detailed Description

In this single-center, open-label, single-arm, prospective clinical trial, a total of 20 recurrent or refractory CD19+ B cell acute lymphoblastic leukemia patients will be enrolled.After recruiting eligible patients,autologous peripheral blood mononuclear cells(PBMCs) will be purified from whole blood.The CD3+ T cells were subsequently selected and re-stimulated by anti-CD3 and anti-CD28 monoclonal antibodies.T cells will be transduced with lentiviral vector for the generation of the CD19 CART cell and administered by i.v. injection.The purpose of current study is to determine the safety and clinical efficacy of CD19 CAR T cells therapy in patients with recurrent or refractory CD19+ ALL.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Recurrent or refractory B cell derived acute lymphoblastic leukemia (ALL)
• Patients who have failed at least one line of a standard treatment without effective treatment measures at present
• CD19 expression on the surface of B-ALL cells must be detected
• KPS>80
• Life expectancy >3 months
• Patients must have adequate cardiac function (no electrocardiogram with obvious abnormality, LVEF≥50%),adequate pulmonary function as indicated by room air oxygen saturation of > 90%, and adequate renal function (Cr≤2.5 times of the normal range)
• The alanine aminotransferase (ALT) and the aspartate aminotransferase (AST)≤ 3 times of the normal range, and the total bilirubin (TBIL)≤2.0mg/dl(34.2umol/L)
• Hemoglobin(Hgb)≥80g/L
• Without contraindication of apheresis and cell isolation
• Patients and their families volunteer to participate in the research with signed written informed consent

Exclusion Criteria:

.Other concurrent severe and/or uncontrolled medical conditions: patients with another primary malignant disease; another severe and/or life-threatening medical disease.

• Evidence of uncontrolled current serious active infection
• HIV/HBV/HCV infection
• Pregnancy and nursing females
• Systemic glucocorticoid therapy within one week

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: B-ALL treated with CD19 CART cell; The qualified CD19-targeted CART cells will be transferred to patient for 3 days as follow:D1,10% fraction;D2,30%;D3 60%. The number of CART cells for each course will be about 1×106/kg. If complete response (CR) or complete response with incomplete hemogram recovery (CRi) in hemogram is achieved after the first course of treatment, further treatment will be decided according to the clinical assessment and the wishes of the patient.If partial response (PR) is achieved after the first course, 1 or 2 courses of treatment will be continued. If there is no response (NR) after the first course, the treatment will be ceased or restarted based on the clinical assessment or patients' wishes. Treatent may be discontinued due to any severe toxicity, such as cytokine release syndrom.

Biological: CD19-targeted CART cells; CD19 CAR T cells was transduced with a lentiviral vector to express anti-CD19 scFv.This is a second generation CRAT.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall response rate(ORR)	ORR is defined as the proportion of partial responses plus complete responses.	Participants will be followed for the duration of the treatment, with an expected average of 3 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival(PFS)	Progression-free survival is defined as the time from enrollment to first observation of progression or date of death (from any cause).	15 years
Overall survival(OS)	Overall survival, defined as the time from enrollment until death due to any cause. For patients who do not die, time to death will be censored at the time of last contact.	15 years

Collaborators and Investigators

• Sponsor: jiuwei cui

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2019
• Primary Completion (Anticipated): December 30, 2020
• Study Completion (Anticipated): December 30, 2021

Study Registration Dates

• First Submitted: July 15, 2018
• First Submitted That Met QC Criteria: July 15, 2018
• First Posted (Actual): July 26, 2018

Study Record Updates

• Last Update Posted (Actual): February 26, 2019
• Last Update Submitted That Met QC Criteria: February 24, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: ALL; CART; Chimeric Antigen Receptor-Modified T Cells; Recurrent B Cell Acute Lymphoblastic Leukemia; refractory B Cell Acute Lymphoblastic Leukemia
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leukemia, B-Cell
• Other Study ID Numbers: FJLU-002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No