Study Evaluating the Efficacy and Safety of PCAR-019 in CD19 Positive Relapsed or Refractory Leukemia and Lymphoma

The purpose of this study is to evaluate the safety and effectiveness of CAR-T cell immunotherapy in patients with CD19 positive relapsed or refractory Leukemia and Lymphoma.

Study Overview

• Status: Unknown
• Conditions: Follicular Lymphoma; Mantle Cell Lymphoma; Chronic Lymphocytic Leukemia; Acute Lymphocytic Leukemia; Diffuse Large Cell Lymphoma; B-cell Prolymphocytic Leukemia
• Intervention / Treatment: Biological: PCAR-019 (anti-CD19 CAR-T cells)

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China, 215123
      • Recruiting
      • PersonGen BioTherapeutics (Suzhou) Co., Ltd.

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

Male and female subjects with CD19+ B cell malignancies in patients with no available curative treatment options (such as autologous or allogeneic SCT) who have limited prognosis (several months to < 2 year survival) with currently available therapies will be enrolled:

1. Eligible diseases: Acute lymphocytic leukemia (ALL), Chronic lymphocytic leukemia (CLL), Follicular lymphoma, Mantle cell lymphoma, B-cell prolymphocytic leukemia, and diffuse large cell lymphoma, previously identified as CD19+.
2. Patients 14 years of age or older, and must have a life expectancy > 12 weeks.
3. Eastern cooperative oncology group (ECOG) performance status of 0-2 or karnofsky performance status (KPS) score is higher than 60.
4. Adequate venous access for apheresis or venous sampling, and no other contraindications for leukapheresis.
5. Females of child-bearing potential must have a negative pregnancy test and all subjects must agree to use an effective method of contraception for up to two weeks after the last infusion of CAR T cells.
6. Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements: White blood cell count (WBC) ≥ 2500c/ml, Platelets ≥ 50×10^9/L, Hb ≥ 6.0g/dL, lymphocyte (LY) ≥ 0.7×10^9/L, LY% ≥ 15%, Alb ≥ 2.8g/dL, serum lipase and amylase < 1.5×upper limit of normal, serum creatinine ≤ 2.5mg/dL, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5×upper limit of normal, serum total bilirubin ≤ 2.0mg/dL. These tests must be conducted within 7 days prior to registration.
7. Ability to give informed consent.

Exclusion Criteria:

1. The transduction efficiency of the T cells is less than 30% or the amplification of the T cells via artificial antigen presenting cell (aAPC) stimulation is less than 5 times.
2. Pregnant or nursing women may not participate.
3. Active HIV, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
4. Serious illness or medical condition which would not permit the patient to be managed according to the protocol, including active uncontrolled infection, major cardiovascular, coagulation disorders, respiratory or immune system, myocardial infarction, cardiac arrhythmias, obstructive/restrictive pulmonary disease, or psychiatric or emotional disorders.
5. History of severe immediate hypersensitivity to any of the agents including cyclophosphamide, fludarabine, or aldesleukin.
6. Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary.
7. The existence of unstable or active ulcers or gastrointestinal bleeding.
8. Patients need anticoagulant therapy (such as warfarin or heparin).
9. Patients need long-term antiplatelet therapy (aspirin at a dose > 300mg/d; clopidogrel at a dose > 75mg/d).
10. Patients using fludarabine or cladribine chemotherapy within 3 months prior to leukapheresis.

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: PCAR-019; Enrolled patients will receive PCAR-019 with a novel specific chimeric antigen receptor targeting CD19 antigen by infusion.	Biological: PCAR-019 (anti-CD19 CAR-T cells); Other Names: chimeric antigen receptor T cells with specificity for CD19

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Phase I: Adverse events attributed to the administration of PCAR-019	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Phase II: Objective Response Rate	2 years

Collaborators and Investigators

• Sponsor: PersonGen BioTherapeutics (Suzhou) Co., Ltd.
• Collaborators: Anhui Provincial Hospital
• Investigators: Principal Investigator: Lin Yang, Ph.D., PersonGen BioTherapeutics (Suzhou) Co., Ltd.; Principal Investigator: Xingbing Wang, Ph.D., Anhui Provincial Hospital; Principal Investigator: Xin Liu, Ph.D., Anhui Provincial Hospital

Study record dates

Study Major Dates

• Study Start: July 1, 2016
• Primary Completion (Anticipated): November 1, 2018
• Study Completion (Anticipated): November 1, 2019

Study Registration Dates

• First Submitted: July 28, 2016
• First Submitted That Met QC Criteria: July 28, 2016
• First Posted (Estimate): August 1, 2016

Study Record Updates

• Last Update Posted (Estimate): August 1, 2016
• Last Update Submitted That Met QC Criteria: July 28, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Leukemia, B-Cell; Lymphoma, B-Cell; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Leukemia; Lymphoma, Mantle-Cell; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid; Leukemia, Prolymphocytic; Leukemia, Prolymphocytic, B-Cell
• Other Study ID Numbers: PG-019-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes