Gene Therapy for B-Cell Non-Hodgkin Lymphoma Using CD19 CAR Gene Transduced T Lymphocytes
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
1 other identifier
interventional
18
1 country
1
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started May 2014
Typical duration for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 16, 2014
CompletedStudy Start
First participant enrolled
May 1, 2014
CompletedFirst Posted
Study publicly available on registry
May 9, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
March 1, 2017
CompletedNovember 6, 2014
November 1, 2014
2.8 years
April 16, 2014
November 4, 2014
Conditions
Keywords
Outcome Measures
Primary Outcomes (6)
Toxicity Profile
Confirm the toxicity profile with CTCAE ver4.0.
12 weeks
Toxicity Profile
Confirm existence or non-existence of normal B-lymphocytes decrease by flow cytometry.
12 weeks
Toxicity Profile
Measure immunoglobulin by PCR.
12 weeks
Toxicity Profile
Confirm replication competent retrovirus (RCR) by PCR.
12 weeks
Toxicity Profile
Confirm clonality by linear amplification mediated (LAM)-PCR.
12 weeks
Quality test of CD19-CAR-T
Transduction efficiency, viability, sterility and potency.
Before administration
Secondary Outcomes (3)
Tumor shrinkage effect
12 weeks
Lymphocyte subset analysis of CD19-CAR-T
12 weeks
Human anti-mouse antibody (HAMA) test
12 weeks
Study Arms (4)
Dose Level -1
EXPERIMENTALCyclophosphamide or Bendamustine as Pre-treatment, and in combination with CD19-CAR-T. In case when sufficient cell number of CD19-CAR-T has been manufactured, the physician judges whether the 2nd infusion of CD19-CAR-T should be performed based on the condition of the subject.
Dose Level 1
EXPERIMENTALCyclophosphamide or Bendamustine as Pre-treatment, and in combination with CD19-CAR-T. In case when sufficient cell number of CD19-CAR-T has been manufactured, the physician judges whether the 2nd infusion of CD19-CAR-T should be performed based on the condition of the subject.
Dose Level 2
EXPERIMENTALCyclophosphamide or Bendamustine as Pre-treatment, and in combination with CD19-CAR-T. In case when sufficient cell number of CD19-CAR-T has been manufactured, the physician judges whether the 2nd infusion of CD19-CAR-T should be performed based on the condition of the subject.
Dose Level 3
EXPERIMENTALCyclophosphamide or Bendamustine as Pre-treatment, and in combination with CD19-CAR-T. In case when sufficient cell number of CD19-CAR-T has been manufactured, the physician judges whether the 2nd infusion of CD19-CAR-T should be performed based on the condition of the subject.
Interventions
Cyclophosphamide \[1.5 g/m\^2 x 1 day Intravenous (IV)\] or Bendamustine \[120 mg/m\^2 x 2 days Intravenous (IV)\] is administered as Pre-treatment medication of CD19-CAR-T.
CD19-CAR-T \[1/3 x 10\^6 cells/kg x 1 day and 2/3 x 10\^6 cells/kg x 1 day Intravenous (IV)\] are administered.
CD19-CAR-T \[1 x 10\^6 cells/kg x 1 day and 2 x 10\^6 cells/kg x 1 day Intravenous (IV)\] are administered.
CD19-CAR-T \[1/3 x 10\^7 cells/kg x 1 day and 2/3 x 10\^7 cells/kg x 1 day Intravenous (IV)\] are administered.
Eligibility Criteria
You may qualify if:
- Relapsed or refractory B-NHL.
- Evaluable region can be identified by CT scan and is positive by FDG-PET.
- ≤ age ≤ 70 years at the time of informed consent.
- ECOG performance status of 0-2.
- Well preserved main organ functions.
- Life expectancy ≥3 months after informed consent.
- Written informed consent.
You may not qualify if:
- Other active malignancy.
- CNS infiltration of lymphoma.
- History of allogeneic stem cell transplantation.
- Already participated in a clinical trial in which CD19-CAR-T are administered within 24 weeks.
- Concurrent use of systemic steroids or immunosuppressive agents.
- Concurrent severe heart disease.
- History of severe cerebrovascular disease or sequela including paralysis.
- Known active or severe infection.
- HIV seropositive status.
- HBsAg-positive or both HBcAb and HBV-DNA positive.
- Active hepatitis C.
- Psychiatric disorder or drug addiction that affects the ability of informed consent.
- Pregnant or breastfeeding women, women who may be pregnant and women desiring to become pregnant. Men who desire impregnating a woman are also excluded (excluded: in case when sperm is cryopreserved prior to gene therapy and a child is born by using the sperm).
- Any other patients judged by the investigators to be inappropriate for the subject of this study.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Jichi Medical Universitylead
- Takara Bio Inc.collaborator
Study Sites (1)
Jichi Medical University
Shimotsuke, Tochigi, 329-0498, Japan
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Keiya Ozawa, MD, PhD
Division of Hematology, Department of Medicine, Center for Molecular Medicine, Division of Genetic Therapeutics, Center for Molecular Medicine, Division of Immuno-Gene & Cell Therapy (Takara Bio), Jichi Medical University
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Professor
Study Record Dates
First Submitted
April 16, 2014
First Posted
May 9, 2014
Study Start
May 1, 2014
Primary Completion
March 1, 2017
Study Completion
March 1, 2017
Last Updated
November 6, 2014
Record last verified: 2014-11