Relapsed or Refractory B-Cell Non-Hodgkin LymphomaPhase 1/2NCT02134262
Gene Therapy for B-Cell Non-Hodgkin Lymphoma Using CD19 CAR Gene Transduced T Lymphocytes
A Phase 1/2 study testing Cyclophosphamide or Bendamustine, Dose Level -1 and Dose Level 1 in people with Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma, run by Jichi Medical University at 1 site in Japan.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 to 70 years
- Conditions the study is for
- Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma
- What is being tested?
- Cyclophosphamide or Bendamustine, Dose Level -1 and Dose Level 1
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteJapan
- Study dates
- May 2014to Mar 2017
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Relapsed or refractory B-NHL.
- Evaluable region can be identified by CT scan and is positive by FDG-PET.
- 20 ≤ 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
Japan1 site, 1 recruiting
- Recruiting
Jichi Medical University
Shimotsuke, Tochigi, 329-0498
Ken Ohmine, MD, PhD, +81-285-58-7353, omineken@jichi.ac.jp
Keiya Ozawa, MD, PhD
About this study
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
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.
Read the detailed description
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.
- Being tested
- Cyclophosphamide or Bendamustine, Dose Level -1, Dose Level 1, Dose Level 2, Dose Level 3
- Keywords
- Anti-CD19 CAR Expressing T cells Therapy, CD19 CAR Gene-Transduced Lymphocyte, Adoptive Immunotherapy, Genetically Engineered Lymphocyte Therapy, Retroviral Vector, Burkitt Lymphoma, Lymphoma, Lymphoma, Follicular, Lymphoma, Non-Hodgkin, Lymphomatoid Granulomatosis, Lymphoma, B-Cell, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Large-Cell, Immunoblastic, Lymphoma, B-Cell, Marginal Zone, Lymphoma, Extranodal NK-T-Cell, Lymphoma, Mantle-Cell, Neoplasms by Histologic Type, Neoplasms, Neoplasms, Experimental, Immune System Diseases
- Medical subject headings
- Recurrence, Lymphoma, B-Cell, Burkitt Lymphoma, Lymphoma, Lymphoma, Follicular, Lymphoma, Non-Hodgkin, Lymphomatoid Granulomatosis, Lymphoma, Large B-Cell, Diffuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cyclophosphamide or BendamustineDrug
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 -1Genetic
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 1Genetic
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 2Genetic
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 3Genetic
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.
| Study group | Role | What they receive |
|---|---|---|
| Dose Level -1 | Experimental | 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. Receives: Drug: Cyclophosphamide or Bendamustine; Genetic: Dose Level -1 |
| Dose Level 1 | Experimental | 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. Receives: Drug: Cyclophosphamide or Bendamustine; Genetic: Dose Level 1 |
| Dose Level 2 | Experimental | 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. Receives: Drug: Cyclophosphamide or Bendamustine; Genetic: Dose Level 2 |
| Dose Level 3 | Experimental | 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. Receives: Drug: Cyclophosphamide or Bendamustine; Genetic: Dose Level 3 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Toxicity Profile
Confirm the toxicity profile with CTCAE ver4.0.
Measured: 12 weeks
Toxicity Profile
Confirm existence or non-existence of normal B-lymphocytes decrease by flow cytometry.
Measured: 12 weeks
Toxicity Profile
Measure immunoglobulin by PCR.
Measured: 12 weeks
Toxicity Profile
Confirm replication competent retrovirus (RCR) by PCR.
Measured: 12 weeks
Toxicity Profile
Confirm clonality by linear amplification mediated (LAM)-PCR.
Measured: 12 weeks
Quality test of CD19-CAR-T
Transduction efficiency, viability, sterility and potency.
Measured: Before administration
Secondary outcomes (3)
Tumor shrinkage effect
Confirm the efficacy with "Revised response criteria for malignant lymphoma" J Clin Oncol. 25: 579-586 (2007).
Measured: 12 weeks
Lymphocyte subset analysis of CD19-CAR-T
Confirm the state of immune mechanism by flow cytometry.
Measured: 12 weeks
Human anti-mouse antibody (HAMA) test
Examine HAMA with ELISA.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2014 (estimated)
- Study startMay 2014
- Primary completionMar 2017 (estimated)
- Study completionMar 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Relapsed or Refractory B-Cell Non-Hodgkin LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Jichi Medical University
- Sponsor type
- University, hospital or other
- Collaborators
- Takara Bio Inc.
- Responsible party
- Principal investigator, Keiya Ozawa, Jichi Medical University
- Investigators
- Keiya Ozawa, MD, PhD, 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
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02134262
- Sponsor's protocol ID
- JMU-CD19CAR
- Status last verified
- Nov 2014
- First submitted
- 16 Apr 2014
- Last updated
- 6 Nov 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02134262
- Acronym / sponsor ID
- JMU-CD19CAR
- Keywords
- Anti-CD19 CAR Expressing T cells Therapy, CD19 CAR Gene-Transduced Lymphocyte, Adoptive Immunotherapy, Genetically Engineered Lymphocyte Therapy, Retroviral Vector, Burkitt Lymphoma, Lymphoma, Lymphoma, Follicular
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- Jichi Medical UniversityUniversity, hospital or other
- Collaborators
- Takara Bio Inc.
- Study start
- May 2014
- Primary completion
- Mar 2017 (estimated)
- Study completion
- Mar 2017 (estimated)
- First posted
- 9 May 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Dose Level -1 | Experimental | Drug: Cyclophosphamide or Bendamustine, Genetic: Dose Level -1Cyclophosphamide 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 | Experimental | Drug: Cyclophosphamide or Bendamustine, Genetic: Dose Level 1Cyclophosphamide 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 | Experimental | Drug: Cyclophosphamide or Bendamustine, Genetic: Dose Level 2Cyclophosphamide 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 | Experimental | Drug: Cyclophosphamide or Bendamustine, Genetic: Dose Level 3Cyclophosphamide 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. |
Who may qualify
- Ages
- 20 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Relapsed or refractory B-NHL.
- Evaluable region can be identified by CT scan and is positive by FDG-PET.
- 20 ≤ age ≤ 70 years at the time of informed consent.
- ECOG performance status of 0-2.
- Well preserved main organ functions.
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cyclophosphamide or BendamustineCyclophosphamide [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. | Drug | Dose Level -1, Dose Level 1, Dose Level 2, Dose Level 3 |
| Dose Level -1CD19-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. | Genetic | Dose Level -1 |
| Dose Level 1CD19-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. | Genetic | Dose Level 1 |
| Dose Level 2CD19-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. | Genetic | Dose Level 2 |
| Dose Level 3CD19-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. | Genetic | Dose Level 3 |
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.
3 secondary outcomes
Tumor shrinkage effect
Time frame: 12 weeks
Lymphocyte subset analysis of CD19-CAR-T
Time frame: 12 weeks
Human anti-mouse antibody (HAMA) test
Time frame: 12 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2014.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Keiya Ozawa, MD, PhD 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
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Cyclophosphamide or Bendamustine, Dose Level -1 and Dose Level 1 in people with Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma, run by Jichi Medical University at 1 site in Japan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 6 Nov 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ken Ohmine, MD, PhD (+81-285-58-7353, omineken@jichi.ac.jp), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Toxicity Profile (time frame: 12 weeks). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Nov 2014.