B-cell LymphomasPhase 1/24SCAR19273NCT02247609
Evaluation of 4th Generation Safety-designed CAR T Cells Targeting High-risk and Refractory B Cell Lymphomas
A Phase 1/2 study testing Anti-CD19 CAR T cells in people with B-cell Lymphomas, run by Peking University at 1 site in China.
Trial summary
Currently, a majority of B cell lymphomas cannot be cured by standard chemo-radiotherapy. Most B cell lymphomas express cluster of differentiation antigen 19 (CD19), which represents a very attractive target for chimeric antigen receptor (CAR)-based immune cell therapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- B-cell Lymphomas
- What is being tested?
- Anti-CD19 CAR T cells
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteChina
- Study dates
- Jan 2014to Oct 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Relapsed or refractory CD19(+) B cell lymphoma patients proved by immuno-histochemistry (IHC) or Flow-cytometry.
- Not eligible for autologous stem-cell transplantation (ASCT) or relapsed after ASCT.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
- Age≥18.
- Pulse oximetry of > 90% on room air.
- Adequate hepatic function, defined as alanine transaminase (ALT) <3 x upper limit of normal (ULN), aspartate aminotransferase (AST) <3 x ULN; serum bilirubin and alkaline phosphatase <2 x ULN.
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- Adequate renal function, defined as serum creatinine <2.0mg/dl.
- Adequate heart function with LVEF≥50%
- Hb≥80g/L
- Measurable disease can be identified.
- Life expectancy ≥3 months.
- Sexually active patients must be willing to utilize one of the more effective birth control methods during the study and for 1 year after the study is concluded. The male partner should use a condom.
- Patients must sign an informed consent.
Who cannot join
- Uncontrolled active infection.
- Active infection with hepatitis B virus (HBV), hepatitis C virus (HCV).
- HIV positive
- Pregnant or lactating.
- Currently enrolled in another clinical trial.
- Concurrent use of systemic steroids.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Peking University Cancer Hospital
Beijing, Beijing Municipality, 100142
Jun Zhu, MD, +86-10-88196596, zj@bjcancer.org
Jun Zhu, MD
About this study
Official title: Safety and Efficacy Evaluation of 4th Generation Safety-engineered CAR T Cells Targeting High-risk and Refractory B Cell Lymphomas
Currently, a majority of B cell lymphomas cannot be cured by standard chemo-radiotherapy. Most B cell lymphomas express cluster of differentiation antigen 19 (CD19), which represents a very attractive target for chimeric antigen receptor (CAR)-based immune cell therapy. This study will evaluate a novel 4th generation CD19 CAR engineered with a self-withdrawal mechanism (19273-4SCAR) for both efficacy and safety in lymphoma patients.
Read the detailed description
CD19 single chain antibody-based chimeric antigen receptor (CAR)-engineered T cells have demonstrated great clinical potential in treating chronic and acute B cell leukemias. B cell lymphomas, similar to B cell leukemias, express CD19 surface molecules, and the majority of the B cell lymphoma patients cannot be cured by standard chemo-radiotherapy. CD19 CAR-based adoptive T cell therapy is associated with an unwanted adverse effect, the loss of CD19 B cells, which results in humoral immune deficiency. This study will evaluate a novel 4th generation CD19 CAR engineered with a self-withdrawal genetic mechanism (19273-4SCAR) for both efficacy and safety in lymphoma patients. The 4th generation design of the CAR incorporates the intracellular signaling domain of cluster of differentiation antigen 27 (CD27), known to be associated with T cell activation, survival and longevity. The inducible caspase 9 self-withdrawal design allows for rapid elimination of the infused CAR T cells upon complete eradication of the tumor cells, which will be followed by the recovery of humoral immunity. Patients receiving the 19273-4SCAR T cells will be closely monitored for infusion response, tumor eradication effect, longevity of the CAR T cells, and the recovery of B cell functions after withdrawal of the CAR T cells.
- Conditions
- B-cell Lymphomas
- Being tested
- Anti-CD19 CAR T cells
- Keywords
- B cell lymphoma, non-Hodgkin's lymphoma, Burkitt lymphoma, diffused large B cell lymphoma, B cell malignancy
- Medical subject headings
- Lymphoma, B-Cell, Lymphoma, Non-Hodgkin, Burkitt Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anti-CD19 CAR T cellsGenetic
Also called 19273-4SCAR
Autologous 4th generation withdrawable lentiviral-transduced anti-CD19-CAR T cells
| Study group | Role | What they receive |
|---|---|---|
| CAR T cells | Experimental | Autologous 4th generation anti-CD19-CAR T cells Receives: Genetic: Anti-CD19 CAR T cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients with adverse events.
Determine the toxicity profile of the 4th generation CAR T cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0.
Measured: 2 years.
Secondary outcomes (3)
Survival time of Anti-CD19 CAR T cells in vivo.
Measure the survival of 4th generation CAR T cells transduced with the anti-CD19 lentiviral vector.
Measured: 2 years.
Response rates to the 4th generation CAR T cells.
Describe the response rates of patients treated with 4th generation CAR T cells, including partial remission (PR), complete remission (CR), stable disease (SD) and progressive disease (PD).
Measured: 2 years.
Survival time of the patients.
Evaluate the survival time of the patients treated with the 4th generation CAR T cells, including progression free survival (PFS) and overall survival (OS).
Measured: 2 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2014 (estimated)
- Study startJan 2014
- Primary completionOct 2016 (estimated)
- Study completionOct 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for B-cell LymphomasStudies of the same condition, open and under way.
- More trials run by Peking UniversityThe sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peking University
- Sponsor type
- University, hospital or other
- Collaborators
- University of Florida
- Responsible party
- Principal investigator, Jun Zhu, Peking University
- Investigators
- Jun Zhu, MD, Principal investigator, Peking University Cancer Hospital & Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02247609
- Sponsor's protocol ID
- 19273-4SCAR
- Acronym
- 4SCAR19273
- Status last verified
- Jan 2014
- First submitted
- 17 Sep 2014
- Last updated
- 20 Oct 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Oct 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy Evaluation of 4th Generation Safety-engineered CAR T Cells Targeting High-risk and Refractory B Cell Lymphomas
- ClinicalTrials.gov ID
- NCT02247609
- Acronym / sponsor ID
- 4SCAR19273 / 19273-4SCAR
- Conditions
- B-cell Lymphomas
- Keywords
- B cell lymphoma, non-Hodgkin's lymphoma, Burkitt lymphoma, diffused large B cell lymphoma, B cell malignancy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Peking UniversityUniversity, hospital or other
- Collaborators
- University of Florida
- Study start
- Jan 2014
- Primary completion
- Oct 2016 (estimated)
- Study completion
- Oct 2017 (estimated)
- First posted
- 25 Sep 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.
Currently, a majority of B cell lymphomas cannot be cured by standard chemo-radiotherapy. Most B cell lymphomas express cluster of differentiation antigen 19 (CD19), which represents a very attractive target for chimeric antigen receptor (CAR)-based immune cell therapy. This study will evaluate a novel 4th generation CD19 CAR engineered with a self-withdrawal mechanism (19273-4SCAR) for both efficacy and safety in lymphoma patients.
Detailed description
CD19 single chain antibody-based chimeric antigen receptor (CAR)-engineered T cells have demonstrated great clinical potential in treating chronic and acute B cell leukemias. B cell lymphomas, similar to B cell leukemias, express CD19 surface molecules, and the majority of the B cell lymphoma patients cannot be cured by standard chemo-radiotherapy. CD19 CAR-based adoptive T cell therapy is associated with an unwanted adverse effect, the loss of CD19 B cells, which results in humoral immune deficiency. This study will evaluate a novel 4th generation CD19 CAR engineered with a self-withdrawal genetic mechanism (19273-4SCAR) for both efficacy and safety in lymphoma patients. The 4th generation design of the CAR incorporates the intracellular signaling domain of cluster of differentiation antigen 27 (CD27), known to be associated with T cell activation, survival and longevity. The inducible caspase 9 self-withdrawal design allows for rapid elimination of the infused CAR T cells upon complete eradication of the tumor cells, which will be followed by the recovery of humoral immunity. Patients receiving the 19273-4SCAR T cells will be closely monitored for infusion response, tumor eradication effect, longevity of the CAR T cells, and the recovery of B cell functions after withdrawal of the CAR T cells.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CAR T cells | Experimental | Genetic: Anti-CD19 CAR T cellsAutologous 4th generation anti-CD19-CAR T cells |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Relapsed or refractory CD19(+) B cell lymphoma patients proved by immuno-histochemistry (IHC) or Flow-cytometry.
- Not eligible for autologous stem-cell transplantation (ASCT) or relapsed after ASCT.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
- Age≥18.
- Pulse oximetry of > 90% on room air.
Key exclusion criteria (6 listed)
- Uncontrolled active infection.
- Active infection with hepatitis B virus (HBV), hepatitis C virus (HCV).
- HIV positive
- Pregnant or lactating.
- Currently enrolled in another clinical trial.
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 |
|---|---|---|
| Anti-CD19 CAR T cellsAlso: 19273-4SCARAutologous 4th generation withdrawable lentiviral-transduced anti-CD19-CAR T cells | Genetic | CAR T cells |
Primary outcome
Number of patients with adverse events.
Time frame: 2 years.
Determine the toxicity profile of the 4th generation CAR T cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0.
3 secondary outcomes
Survival time of Anti-CD19 CAR T cells in vivo.
Time frame: 2 years.
Response rates to the 4th generation CAR T cells.
Time frame: 2 years.
Survival time of the patients.
Time frame: 2 years.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Oct 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.
Jun Zhu, MD principal investigator
Peking University Cancer Hospital & Institute
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 Anti-CD19 CAR T cells in people with B-cell Lymphomas, run by Peking University at 1 site in China.
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 13 inclusion and 6 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 20 Oct 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 China. 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 Jun Zhu, MD (+86-10-88196596, zj@bjcancer.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of patients with adverse events. (time frame: 2 years.). 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 20 Oct 2014.