B-cell LeukemiaPhase 2NCT03068416
CD19-targeting, 3rd Generation CAR T Cells for Refractory B Cells Malignancy
A Phase 2 study testing CAR T cells in people with B-cell Leukemia and B-Cell Lymphoma, run by Uppsala University at 1 site in Sweden.
Trial summary
Treatment of patients with B cell lymphoma or leukemia with two doses of CD19-targeting chimeric antigen receptor (CAR) T cells to evaluate for safety and efficacy. Read more about this study
- Who is it for?
- Ages 0 to 100 years
- Conditions the study is for
- B-cell Leukemia, B-Cell Lymphoma
- What is being tested?
- CAR T cells
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteSweden
- Study dates
- 18 Sep 2017to 19 Aug 2021
- Phase
- Phase 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 0 to 100 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Relapsed or refractory CD19+ B-cell lymphoma or leukemia with no other curative treatment option available.
- Measurable disease.
- All ages
- Performance status ECOG 0-2.
- 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 to perform the treatment.
- Treatment with an investigational product within 30 days prior to enrollment, or at least 5 half-lives of that drug, which is longest.
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- Pregnancy
- Patients that do not consent to that tissue and blood samples are stored in a biobank
- Patients whose cells cannot be manufactured.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: CD19-targeting, 3rd Generation CAR T Cells for Refractory B Cells Malignancy - a Phase II Trial.
Treatment of patients with B cell lymphoma or leukemia with two doses of CD19-targeting chimeric antigen receptor (CAR) T cells to evaluate for safety and efficacy.
Read the detailed description
Treatment of patients with B cell lymphoma or leukemia with two doses of CD19-targeting chimeric antigen receptor (CAR) T cells to evaluate for safety and efficacy. 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 the second infusion patients will be subjected to immunomodulatory treatment. After T cell infusion, the patients will be evaluated for 24 months for adverse reactions, persistence of CAR T cells and efficacy.
Primary outcome:
- Registration of the safety profile such as inflammation, fever, pain, changes in blood pressure, pulse and other adverse events.
Weekly for the first 6 weeks, then at 3, 6, 9, 12, 15, 18, 21 and 24 months.
Secondary outcome:
Tumor response, CAR T cell persistence and immunological profile
- Determination of tumor size and the tumor marker CD19.
- Determination of the levels of circulating B cells.
- Determination of the level of CAR T cells (mRNA and cells) in blood and biopsies.
- Determination of activation markers on CAR T cells such as CD107a.
- Determination of the presence of immunological markers in blood and biopsies.
At 1 and 3 weeks then at 3, 6, 9, 12, 15, 18, 21 and 24 months.
- Conditions
- B-cell Leukemia, B-Cell Lymphoma
- Being tested
- CAR T cells
- Medical subject headings
- Leukemia, B-Cell, Lymphoma, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CAR T cellsBiological
Autologous CD19-targeting, 3rd generation CAR T cells
| Study group | Role | What they receive |
|---|---|---|
| CAR T cells | Experimental | Autologous 3rd generation CD19-targeting CAR T cells Receives: Biological: CAR T cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Measured: 24 months
Secondary outcomes (5)
Tumor response
Determination of tumor size
Measured: 24 months.
B cell levels
Determination of circulating CD19+ B cells
Measured: 24 months
CAR T cell persistence
Determination of the level of CAR T cells
Measured: 24 months
Immunological profile
Determination of frequencies of immune cells in patient blood and tissues
Measured: 24 months
Cytokine profile
Determination of cytokine profile in patient blood
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Mar 2017
- Study start18 Sep 2017
- Primary completion19 Aug 2021
- Study completion19 Aug 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for B-cell LeukemiaStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Uppsala University
- Sponsor type
- University, hospital or other
- Collaborators
- Uppsala University Hospital, AFA Insurance
- Responsible party
- Sponsor
- Investigators
- Gunilla Enblad, MD, PhD, Principal investigator, Uppsala University Hospital, Dept of Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03068416
- Sponsor's protocol ID
- 004:TCELL
- Other IDs
- 2016-004043-36, 2016
- Status last verified
- Oct 2021
- First submitted
- 21 Feb 2017
- Last updated
- 20 Oct 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Saren T, Ramachandran M, Gammelgard G, Lovgren T, Mirabello C, Bjorklund AK, Wikstrom K, Hashemi J, Freyhult E, Ahlstrom H, Amini RM, Hagberg H, Loskog A, Enblad G, Essand M. Single-Cell RNA Analysis Reveals Cell-Intrinsic Functions of CAR T Cells Correlating with Response in a Phase II Study of Lymphoma Patients. Clin Cancer Res. 2023 Oct 13;29(20):4139-4152. doi: 10.1158/1078-0432.CCR-23-0178.
PubMed 37540566
Study at a glance
From the registry record, last updated by the sponsor on 20 Oct 2021. 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 Cells Malignancy - a Phase II Trial.
- ClinicalTrials.gov ID
- NCT03068416
- Acronym / sponsor ID
- 004:TCELL
- Conditions
- B-cell Leukemia, B-Cell Lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Uppsala UniversityUniversity, hospital or other
- Collaborators
- Uppsala University Hospital, AFA Insurance
- Study start
- 18 Sep 2017 (actual)
- Primary completion
- 19 Aug 2021 (actual)
- Study completion
- 19 Aug 2021 (actual)
- First posted
- 1 Mar 2017 (actual)
- 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.
Treatment of patients with B cell lymphoma or leukemia with two doses of CD19-targeting chimeric antigen receptor (CAR) T cells to evaluate for safety and efficacy.
Detailed description
Treatment of patients with B cell lymphoma or leukemia with two doses of CD19-targeting chimeric antigen receptor (CAR) T cells to evaluate for safety and efficacy. 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 the second infusion patients will be subjected to immunomodulatory treatment. After T cell infusion, the patients will be evaluated for 24 months for adverse reactions, persistence of CAR T cells and efficacy.
Primary outcome:
- Registration of the safety profile such as inflammation, fever, pain, changes in blood pressure, pulse and other adverse events.
Weekly for the first 6 weeks, then at 3, 6, 9, 12, 15, 18, 21 and 24 months.
Secondary outcome:
Tumor response, CAR T cell persistence and immunological profile
- Determination of tumor size and the tumor marker CD19.
- Determination of the levels of circulating B cells.
- Determination of the level of CAR T cells (mRNA and cells) in blood and biopsies.
- Determination of activation markers on CAR T cells such as CD107a.
- Determination of the presence of immunological markers in blood and biopsies.
At 1 and 3 weeks then at 3, 6, 9, 12, 15, 18, 21 and 24 months.
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: CAR T cellsAutologous 3rd generation CD19-targeting CAR T cells |
Who may qualify
- Ages
- 0 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- Relapsed or refractory CD19+ B-cell lymphoma or leukemia with no other curative treatment option available.
- Measurable disease.
- All ages
- Performance status ECOG 0-2.
- Fertile females/males must consent to use contraceptives during participation of the trial.
Key exclusion criteria (9 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 to perform the treatment.
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 |
|---|---|---|
| CAR T cellsAutologous CD19-targeting, 3rd generation CAR T cells | Biological | CAR T cells |
Primary outcome
Safety
Time frame: 24 months
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
5 secondary outcomes
Tumor response
Time frame: 24 months.
B cell levels
Time frame: 24 months
CAR T cell persistence
Time frame: 24 months
Immunological profile
Time frame: 24 months
Cytokine profile
Time frame: 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 20 Oct 2021.
- Derived from this study: PubMed 37540566Saren T, Ramachandran M, Gammelgard G, Lovgren T, Mirabello C, Bjorklund AK, Wikstrom K, Hashemi J, Freyhult E, Ahlstrom H, Amini RM, Hagberg H, Loskog A, Enblad G, Essand M. Single-Cell RNA Analysis Reveals Cell-Intrinsic Functions of CAR T Cells Correlating with Response in a Phase II Study of Lymphoma Patients. Clin Cancer Res. 2023 Oct 13;29(20):4139-4152. doi: 10.1158/1078-0432.CCR-23-0178.
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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.
Gunilla Enblad, MD, PhD principal investigator
Uppsala University Hospital, Dept of Oncology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing CAR T cells in people with B-cell Leukemia and B-Cell Lymphoma, 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 9 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 20 Oct 2021. 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 phase mean?
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?
Safety (time frame: 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 NCT03068416, which also lists 1 linked publication.
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 2021.