B Cell LymphomaPhase 1/2NCT02132624
CD19-targeting 3rd Generation CAR T Cells for Refractory B Cell Malignancy - a Phase I/IIa Trial.
A Phase 1/2 study testing Autologous 3rd generation CD19-targeting CAR T cells in people with B Cell Lymphoma and B Cell Leukemia, run by Uppsala University at 1 site in Sweden.
Trial summary
Chimeric antigen receptor (CAR) T cells targeting CD19 will be evaluated for safety and efficacy in patients with B cell lymphoma or leukemia. The CAR consists of a CD19 targeting antibody scFv with three intracellular signaling domains derived from CD3 zeta, CD28 and 4-1BB. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- B Cell Lymphoma, B Cell Leukemia
- What is being tested?
- Autologous 3rd generation CD19-targeting CAR T cells
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteSweden
- Study dates
- Apr 2014to 31 May 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 or leukemia.
- Measurable disease.
- Performance status ECOG 0-2.
- >18 years old.
- Fertile females/males must consent to use contraceptives during participation of the trial.
- Signed informed consent.
Who cannot join
- Any significant medical or psychiatric illness that would prevent the patient from giving informed consent or from following the study procedures.
- Patients with primary CNS lymphoma.
- Known human immunodeficiency virus (HIV) infection.
- Active and/or severe infection (e.g. tuberculosis, sepsis and opportunistic infections, active hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection).
- Other serious underlying medical conditions, which, in the Investigator's judgment, could impair the ability of the patient.
- Treatment with an investigational product within 30 days prior to enrollment, or at least 5 half lives of that drug, which is longest.
- Patients that do not consent to that tissue and blood samples are stored in a biobank.
- Pregnancy
Trial locations and contacts
1 site in 1 country.
About this study
Chimeric antigen receptor (CAR) T cells targeting CD19 will be evaluated for safety and efficacy in patients with B cell lymphoma or leukemia. The CAR consists of a CD19 targeting antibody scFv with three intracellular signaling domains derived from CD3 zeta, CD28 and 4-1BB. Autologous T cells will be gene engineered with the CAR gene using a retrovirus vector. Prior to T cell infusion, the patients will be subjected to preconditioning treatment. After T cell infusion, the patients will be evaluated for 24 months for adverse reactions, persistence of CAR T cells and efficacy.
- Conditions
- B Cell Lymphoma, B Cell Leukemia
- Being tested
- Autologous 3rd generation CD19-targeting CAR T cells
- Medical subject headings
- Lymphoma, B-Cell, Leukemia, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Autologous 3rd generation CD19-targeting CAR T cellsBiological
Autologous CD19-targeting CAR T cells with three signaling domains derived from CD3zeta, CD28 and 4-1BB.
| Study group | Role | What they receive |
|---|---|---|
| CAR T cells | Experimental | Autologous 3rd generation CD19-targeting CAR T cells Receives: Biological: Autologous 3rd generation CD19-targeting CAR T cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
CAR T cell persistence
Presence of circulating CAR T cells will be evaluated with flow cytometry and real time PCR in patient blood.
Measured: At week 1 and 5, there after every 3 months post treatment up to 24 months
Secondary outcomes (1)
Tumor load
Tumor load will be quantified with radiology, bone marrow and/or blood samples dependent on diagnosis.
Measured: Every 3 months post treatment up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2014 (estimated)
- Study startApr 2014
- Primary completion31 May 2017
- Study completion31 May 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for B Cell 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Uppsala University
- Sponsor type
- University, hospital or other
- Collaborators
- Uppsala University Hospital, Karolinska University Hospital, AFA Insurance, Swedish Cancer Society
- Responsible party
- Sponsor
- Investigators
- Angelica Loskog, PhD, Study director, Uppsala UniversityGunilla Enblad, MD, PhD, Principal investigator, Uppsala University HospitalHans Hagberg, MD, PhD, Principal investigator, Uppsala University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02132624
- Sponsor's protocol ID
- 003:TCELL
- Other IDs
- 2013-001393-19
- Status last verified
- Oct 2017
- First submitted
- 5 May 2014
- Last updated
- 30 Oct 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.
PubMed 34515338Enblad G, Karlsson H, Gammelgard G, Wenthe J, Lovgren T, Amini RM, Wikstrom KI, Essand M, Savoldo B, Hallbook H, Hoglund M, Dotti G, Brenner MK, Hagberg H, Loskog A. A Phase I/IIa Trial Using CD19-Targeted Third-Generation CAR T Cells for Lymphoma and Leukemia. Clin Cancer Res. 2018 Dec 15;24(24):6185-6194. doi: 10.1158/1078-0432.CCR-18-0426. Epub 2018 Aug 10.
PubMed 30097433
Study at a glance
From the registry record, last updated by the sponsor on 30 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CD19-targeting 3rd Generation CAR T Cells for Refractory B Cell Malignancy - a Phase I/IIa Trial.
- ClinicalTrials.gov ID
- NCT02132624
- Acronym / sponsor ID
- 003:TCELL
- Conditions
- B Cell Lymphoma, B Cell Leukemia
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Uppsala UniversityUniversity, hospital or other
- Collaborators
- Uppsala University Hospital, Karolinska University Hospital, AFA Insurance, Swedish Cancer Society
- Study start
- Apr 2014
- Primary completion
- 31 May 2017 (actual)
- Study completion
- 31 May 2017 (actual)
- First posted
- 7 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.
Chimeric antigen receptor (CAR) T cells targeting CD19 will be evaluated for safety and efficacy in patients with B cell lymphoma or leukemia. The CAR consists of a CD19 targeting antibody scFv with three intracellular signaling domains derived from CD3 zeta, CD28 and 4-1BB. Autologous T cells will be gene engineered with the CAR gene using a retrovirus vector. Prior to T cell infusion, the patients will be subjected to preconditioning treatment. After T cell infusion, the patients will be evaluated for 24 months for adverse reactions, persistence of CAR T cells and efficacy.
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 | Biological: Autologous 3rd generation CD19-targeting CAR T cellsAutologous 3rd generation CD19-targeting 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 (6 listed)
- Relapsed or refractory CD19+ B-cell lymphoma or leukemia.
- Measurable disease.
- Performance status ECOG 0-2.
- >18 years old.
- Fertile females/males must consent to use contraceptives during participation of the trial.
Key exclusion criteria (8 listed)
- Any significant medical or psychiatric illness that would prevent the patient from giving informed consent or from following the study procedures.
- Patients with primary CNS lymphoma.
- Known human immunodeficiency virus (HIV) infection.
- Active and/or severe infection (e.g. tuberculosis, sepsis and opportunistic infections, active hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection).
- Other serious underlying medical conditions, which, in the Investigator's judgment, could impair the ability of the patient.
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 |
|---|---|---|
| Autologous 3rd generation CD19-targeting CAR T cellsAutologous CD19-targeting CAR T cells with three signaling domains derived from CD3zeta, CD28 and 4-1BB. | Biological | CAR T cells |
Primary outcome
CAR T cell persistence
Time frame: At week 1 and 5, there after every 3 months post treatment up to 24 months
Presence of circulating CAR T cells will be evaluated with flow cytometry and real time PCR in patient blood.
1 secondary outcome
Tumor load
Time frame: Every 3 months post treatment up to 24 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2017.
- Derived from this study: PubMed 34515338Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.
- Derived from this study: PubMed 30097433Enblad G, Karlsson H, Gammelgard G, Wenthe J, Lovgren T, Amini RM, Wikstrom KI, Essand M, Savoldo B, Hallbook H, Hoglund M, Dotti G, Brenner MK, Hagberg H, Loskog A. A Phase I/IIa Trial Using CD19-Targeted Third-Generation CAR T Cells for Lymphoma and Leukemia. Clin Cancer Res. 2018 Dec 15;24(24):6185-6194. doi: 10.1158/1078-0432.CCR-18-0426. Epub 2018 Aug 10.
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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.
Angelica Loskog, PhD study director
Uppsala University
Gunilla Enblad, MD, PhD principal investigator
Uppsala University Hospital
Hans Hagberg, MD, PhD principal investigator
Uppsala University Hospital
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 Autologous 3rd generation CD19-targeting CAR T cells in people with B Cell Lymphoma and B Cell Leukemia, run by Uppsala University at 1 site in Sweden.
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 6 inclusion and 8 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: finished, as of the sponsor's last update on 30 Oct 2017. 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 Sweden. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
CAR T cell persistence (time frame: At week 1 and 5, there after every 3 months post treatment up to 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02132624, which also lists 2 linked publications.
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 30 Oct 2017.