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

NCT ID: NCT02134262

Last Updated: 2014-11-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE1/PHASE2

Total Enrollment

18 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-05-31

Study Completion Date

2017-03-31

Brief Summary

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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 Description

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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 frequency of once a year for 15 years after the 1st infusion of CD19-CAR-T in reference to guidelines of FDA.

Conditions

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Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Dose Level -1

Cyclophosphamide 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.

Group Type EXPERIMENTAL

Cyclophosphamide or Bendamustine

Intervention Type DRUG

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.

Dose Level -1

Intervention Type GENETIC

CD19-CAR-T \[1 x 10\^5 cells/kg x 1 day and 2 x 10\^5 cells/kg x 1 day Intravenous (IV)\] are administered.

Dose Level 1

Cyclophosphamide 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.

Group Type EXPERIMENTAL

Cyclophosphamide or Bendamustine

Intervention Type DRUG

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.

Dose Level 1

Intervention Type GENETIC

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.

Dose Level 2

Cyclophosphamide 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.

Group Type EXPERIMENTAL

Cyclophosphamide or Bendamustine

Intervention Type DRUG

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.

Dose Level 2

Intervention Type GENETIC

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.

Dose Level 3

Cyclophosphamide 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.

Group Type EXPERIMENTAL

Cyclophosphamide or Bendamustine

Intervention Type DRUG

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.

Dose Level 3

Intervention Type GENETIC

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.

Interventions

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Cyclophosphamide or Bendamustine

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.

Intervention Type DRUG

Dose Level -1

CD19-CAR-T \[1 x 10\^5 cells/kg x 1 day and 2 x 10\^5 cells/kg x 1 day Intravenous (IV)\] are administered.

Intervention Type GENETIC

Dose Level 1

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.

Intervention Type GENETIC

Dose Level 2

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.

Intervention Type GENETIC

Dose Level 3

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.

Intervention Type GENETIC

Eligibility Criteria

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Inclusion Criteria

1. Relapsed or refractory B-NHL.
2. Evaluable region can be identified by CT scan and is positive by FDG-PET.
3. 20 ≤ age ≤ 70 years at the time of informed consent.
4. ECOG performance status of 0-2.
5. Well preserved main organ functions.
6. Life expectancy ≥3 months after informed consent.
7. Written informed consent.

Exclusion Criteria

1. Other active malignancy.
2. CNS infiltration of lymphoma.
3. History of allogeneic stem cell transplantation.
4. Already participated in a clinical trial in which CD19-CAR-T are administered within 24 weeks.
5. Concurrent use of systemic steroids or immunosuppressive agents.
6. Concurrent severe heart disease.
7. History of severe cerebrovascular disease or sequela including paralysis.
8. Known active or severe infection.
9. HIV seropositive status.
10. HBsAg-positive or both HBcAb and HBV-DNA positive.
11. Active hepatitis C.
12. Psychiatric disorder or drug addiction that affects the ability of informed consent.
13. 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).
14. Any other patients judged by the investigators to be inappropriate for the subject of this study.
Minimum Eligible Age

20 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Takara Bio Inc.

INDUSTRY

Sponsor Role collaborator

Jichi Medical University

OTHER

Sponsor Role lead

Responsible Party

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Keiya Ozawa

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Keiya Ozawa, MD, PhD

Role: STUDY_CHAIR

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

Locations

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Jichi Medical University

Shimotsuke, Tochigi, Japan

Site Status RECRUITING

Countries

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Japan

Central Contacts

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Ken Ohmine, MD, PhD

Role: CONTACT

+81-285-58-7353

Keiya Ozawa, MD, PhD

Role: CONTACT

+81-285-58-7353

Facility Contacts

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Ken Ohmine, MD, PhD

Role: primary

+81-285-58-7353

Other Identifiers

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JMU-CD19CAR

Identifier Type: -

Identifier Source: org_study_id

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