UMIN-CTR Clinical Trial

Unique ID issued by UMIN UMIN000015617
Receipt number R000018149
Scientific Title Clinical Research of gene therapy for relapsed or refractory B-cell Non-Hodgkin Lymphoma using autologous T cells expressing a chimeric antigen receptor specific to the CD19 antigen
Date of disclosure of the study information 2014/11/06
Last modified on 2014/11/06 14:19:16

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Basic information

Public title

Clinical Research of gene therapy for relapsed or refractory B-cell Non-Hodgkin Lymphoma using autologous T cells expressing a chimeric antigen receptor specific to the CD19 antigen

Acronym

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

Scientific Title

Clinical Research of gene therapy for relapsed or refractory B-cell Non-Hodgkin Lymphoma using autologous T cells expressing a chimeric antigen receptor specific to the CD19 antigen

Scientific Title:Acronym

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

Region

Japan


Condition

Condition

Relapsed/Refractory CD19+ B-NHL

Classification by specialty

Hematology and clinical oncology

Classification by malignancy

Malignancy

Genomic information

NO


Objectives

Narrative objectives1

Evaluate the safety, efficacy and blood kinetics of autologous T cells genetically modified to express anti-CD19 chimeric antigen receptor (CAR)

Basic objectives2

Safety

Basic objectives -Others


Trial characteristics_1

Exploratory

Trial characteristics_2

Pragmatic

Developmental phase

Phase I,II


Assessment

Primary outcomes

# Quality test of anti-CD19 CAR expressing T cells (CD19-CAR-T)
# Safety: Adverse events, laboratory tests (hematology, serum chemistry, immunological, and infectious disease)
# Replication competent retrovirus (RCR) test
# Linear amplification mediated-PCR (LAM-PCR)

Key secondary outcomes

# Antitumor effect of CD19-CAR-T
# Lymphocyte subset analysis of CD19-CAR-T
# Immunogenicity of CD19-CAR-T


Base

Study type

Interventional


Study design

Basic design

Single arm

Randomization

Non-randomized

Randomization unit


Blinding

Open -no one is blinded

Control

Uncontrolled

Stratification


Dynamic allocation


Institution consideration


Blocking


Concealment



Intervention

No. of arms

1

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

# Dose level -1; 0-6 patients
1. Pre-treatment: Cyclophosphamide
1.5 g/m^2 * 1 day i.v. (Day -2)
or Bendamustine
120 mg/m^2 * 2 days i.v.
(Day -3, Day -2)
2. Infusion of CD19-CAR-T cells
3 * 10^5 cells/kg, a split dose
(Day 0: 1/3 dose, Day 1: 2/3 dose)

# Dose level 1(Starting Dose);
3-6 patients
1. Pre-treatment: Cyclophosphamide
1.5 g/m^2 * 1 day i.v. (Day -2)
or Bendamustine
120 mg/m^2 * 2 days i.v.
(Day -3, Day-2)
2. Infusion of CD19-CAR-T cells
1 *10^6 cells/kg, a split dose
(Day 0: 1/3 dose, Day 1: 2/3 dose)

# Dose level 2; 0-6 patients
1. Pre-treatment: Cyclophosphamide
1.5 g/m^2 * 1 day i.v. (Day -2)
or Bendamustine
120 mg/m^2 * 2 days i.v.
(Day -3, Day-2)
2. Infusion of CD19-CAR-T cells
3 * 10^6 cells/kg, a split dose
(Day 0: 1/3 dose, Day 1: 2/3 dose)

# Dose level 3; 0-6 patients
1. Pre-treatment: Cyclophosphamide
1.5 g/m^2 * 1 day i.v. (Day -2)
or Bendamustine
120 mg/m^2 * 2 days i.v.
(Day -3, Day-2)
2. Infusion of CD19-CAR-T cells
1 *10^7 cells/kg, a split dose
(Day 0: 1/3 dose, Day 1: 2/3 dose)

Interventions/Control_2


Interventions/Control_3


Interventions/Control_4


Interventions/Control_5


Interventions/Control_6


Interventions/Control_7


Interventions/Control_8


Interventions/Control_9


Interventions/Control_10



Eligibility

Age-lower limit

20 years-old <=

Age-upper limit

70 years-old >=

Gender

Male and Female

Key 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 function below.
1) Neutrophil count >=1,500/micro liter
(excluded: neutropenia due to marrow infiltration of lymphoma)
2) Platelet count >= 10*10^4/micro liter
(excluded: thrombocytopenia due to bone marrow infiltration of lymphoma)
3) T-bil <= 2.0 mg/dL
(excluded: the abnormally value due to hepatobiliary of lymphoma)
4) ALT (GPT)/AST (GOT) <= 150 IU/dL
(excluded: the abnormally value due to hepatic infiltration of lymphoma)
5) ALP <= 1.5 * upper limit of normal (ULN)
(excluded: the abnormally value due to hepatobiliary of lymphoma)
6) Serum creatinine <= 2.0 mg/dL
7) SpO2 >= 92% (without oxygen inhalation)
6. Life expectancy >= 3 months after informed consent.
7. Written informed consent.

Key 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.

Target sample size

18


Research contact person

Name of lead principal investigator

1st name
Middle name
Last name Keiya Ozawa

Organization

Jichi Medical University

Division name

Division of Immuno-Gene& Cell Therapy(Takara Bio)

Zip code


Address

3311-1 Yakushiji, Shimotsuke, Tochigi

TEL

0285-58-7353

Email

kozawa@ms2.jichi.ac.jp


Public contact

Name of contact person

1st name
Middle name
Last name Ken Ohmine

Organization

Jichi Medical University

Division name

Division of Immuno-Gene& Cell Therapy(Takara Bio)

Zip code


Address

3311-1 Yakushiji, Shimotsuke, Tochigi

TEL

0285-58-7353

Homepage URL


Email

omineken@jichi.ac.jp


Sponsor or person

Institute

Jichi Medical University

Institute

Department

Personal name



Funding Source

Organization

Takara Bio Inc.

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Japan


Other related organizations

Co-sponsor

Takara Bio Inc.

Name of secondary funder(s)

Jichi Medical University


IRB Contact (For public release)

Organization


Address


Tel


Email



Secondary IDs

Secondary IDs

YES

Study ID_1

NCT02134262

Org. issuing International ID_1

ClinicalTrials.gov

Study ID_2


Org. issuing International ID_2


IND to MHLW



Institutions

Institutions

自治医科大学附属病院(栃木県)


Other administrative information

Date of disclosure of the study information

2014 Year 11 Month 06 Day


Related information

URL releasing protocol


Publication of results

Unpublished


Result

URL related to results and publications


Number of participants that the trial has enrolled


Results


Results date posted


Results Delayed


Results Delay Reason


Date of the first journal publication of results


Baseline Characteristics


Participant flow


Adverse events


Outcome measures


Plan to share IPD


IPD sharing Plan description



Progress

Recruitment status

Open public recruiting

Date of protocol fixation

2014 Year 10 Month 01 Day

Date of IRB


Anticipated trial start date

2014 Year 11 Month 06 Day

Last follow-up date


Date of closure to data entry


Date trial data considered complete


Date analysis concluded



Other

Other related information



Management information

Registered date

2014 Year 11 Month 06 Day

Last modified on

2014 Year 11 Month 06 Day



Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000018149


Research Plan
Registered date File name

Research case data specifications
Registered date File name

Research case data
Registered date File name