Clinical Trial: Gene Therapy for B-Cell Non-Hodgkin Lymphoma Using CD19 CAR Gene Transduced T Lymphocytes

Study Status: Not yet recruiting
Recruit Status: Unknown status
Study Type: Interventional

Official Title: Clinical Research of Gene Therapy for Refractory B-Cell Non-Hodgkin Lymphoma Using Autologous T Cells Expressing a Chimeric Antigen Receptor Specific to the CD19 Antigen

Brief Summary: The purpose of this study is to evaluate the safety, efficacy and blood kinetics of autologous T cells genetically modified to express anti-CD19 Chimeric Antigen Receptor in patients with relapsed or refractory B-Cell Non-Hodgkin Lymphoma.

Detailed Summary:

Peripheral blood (up to 600 mL) will be collected from a subject after obtaining a written informed consent and completing the 1st registration. Peripheral blood mononuclear cells (PBMCs) and plasma are obtained from the blood, and T cells contained in the PBMCs are transduced with anti-CD19 CAR gene by using SFG-1928z retroviral vector. Anti-CD19 CAR expressing T cells (CD19-CAR-T) will be expanded using a medium containing autologous plasma. After the T cells pass in quality control tests, the subject will go into 2nd registration. Subjects will be hospitalized and administered Cyclophosphamide on Day -2 or Bendamustine on Day -3 to Day -2 intravenously as Pre-treatment, and then subjects will receive 1st infusion of CD19-CAR-T on Day 0 and Day 1 (Day 1：1/3 dose, Day 2：2/3 dose) as a split dose. In case the sufficient cell number of CD19-CAR-T is manufactured, DLT is not observed after CD19-CAR-T infusion, certain clinical effect is observed and additional treatment is preferable, the necessity of 2nd infusion will be assessed. In the case that 2nd infusion is necessary, it is allowed to infuse at appropriate timing.

This study is conducted based on the 3+3 dose escalation scheme. Three subjects are enrolled in each group of Dose Level. If one of the 3 subjects show DLT during DLT assessment period, another 3 subjects will be added; therefore, decision as to whether the next Dose Level can follow or not is made based on the results obtained from the total of 6 subjects.

The investigator assesses the tumor shrinkage effect of CD19-CAR-T in accordance with "Revised response criteria malignant lymphoma", at 12 week after the 1st infusion of CD19-CAR-T (or at the time of termination). The investigator also assesses the safety during the follow-up period. Long-term follow-up study is conducted at frequ
Sponsor: Jichi Medical University

Current Primary Outcome:

  • Toxicity Profile [ Time Frame: 12 weeks ]
    Confirm the toxicity profile with CTCAE ver4.0.
  • Toxicity Profile [ Time Frame: 12 weeks ]
    Confirm existence or non-existence of normal B-lymphocytes decrease by flow cytometry.
  • Toxicity Profile [ Time Frame: 12 weeks ]
    Measure immunoglobulin by PCR.
  • Toxicity Profile [ Time Frame: 12 weeks ]
    Confirm replication competent retrovirus (RCR) by PCR.
  • Toxicity Profile [ Time Frame: 12 weeks ]
    Confirm clonality by linear amplification mediated (LAM)-PCR.
  • Quality test of CD19-CAR-T [ Time Frame: Before administration ]
    Transduction efficiency, viability, sterility and potency.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Tumor shrinkage effect [ Time Frame: 12 weeks ]
    Confirm the efficacy with "Revised response criteria for malignant lymphoma" J Clin Oncol. 25: 579-586 (2007).
  • Lymphocyte subset analysis of CD19-CAR-T [ Time Frame: 12 weeks ]
    Confirm the state of immune mechanism by flow cytometry.
  • Human anti-mouse antibody (HAMA) test [ Time Frame: 12 weeks ]
    Examine HAMA with ELISA.


Original Secondary Outcome: Same as current

Information By: Jichi Medical University

Dates:
Date Received: April 16, 2014
Date Started: May 2014
Date Completion: March 2017
Last Updated: November 4, 2014
Last Verified: November 2014