Diffuse Large B-cell LymphomaPhase 1PORTIANCT03630159
Study of Tisagenlecleucel in Combination With Pembrolizumab in r/r Diffuse Large B-cell Lymphoma Patients
A Phase 1 study testing Tisagenlecleucel and Pembrolizumab in people with Diffuse Large B-cell Lymphoma, run by Novartis Pharmaceuticals at 5 sites in 3 countries.
Trial summary
A multi-center, open-label, phase Ib study to evaluate the safety and efficacy of the administration of tisagenlecleucel in combination with pembrolizumab in patients with r/r DLBCL who have received 2 or more lines of systemic therapy, including an anti-CD20 and anthracycline based chemotherapy and having failed to… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diffuse Large B-cell Lymphoma
- What is being tested?
- Tisagenlecleucel and Pembrolizumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 5 sitesin 3 countries
- Study dates
- 9 Oct 2018to 20 Jul 2021
- Phase
- Phase 1
- 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
- Confirmed DLBCL per local histopathology assessment.
- Relapsed or refractory disease after having recieved 2 or more lines of systemic therapy, including anti-CD20 and anthracycline based chemotherapy, and either having progressed after (or relapsed after) ASCT, or being not candidates for or not consenting to ASCT.
- Measurable disease at time of enrollment
- ECOG performance status that is either 0 or 1 at screening.
Who cannot join
- Patients with Richter's transformation, and Burkitt lymphoma, and primary DLBCL of CNS.
- Prior treatment with any prior anti-CD19/anti-CD3 therapy, or any other anti-CD19 therapy.
- Patients with active CNS involvement are excluded, except if the CNS involvement has been effectively treated and provided that local treatment was >4 weeks before enrollment.
- Prior allogeneic HSCT.
- Unstable angina and/or myocardial infarction and/or coronary artery bypass graft (CABG), or stroke within 6 months prior to screening, and/or impaired cardiac function or clinically significant cardiac disease
- Patients with a history of prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibodies, other immune checkpoint inhibitors.
- History of interstitial lung disease or (non-infectious) pneumonitis that required oral or intravenous steroids (other than COPD exacerbation) or current pneumonitis.
- Other protocol-defined inclusion/exclusion criteria may apply.
Trial locations and contacts
5 sites in 3 countries.
5 sites in 3 countries
United States3 sites
Emory University School of Medicine SC CTL019
Atlanta, Georgia, 30322
University of Chicago Medical Center Hematology and Oncology
Chicago, Illinois, 60637
University of Kansas Hospital and Medical Center U of Kansas Cancer Center
Kansas City, Kansas, 66160
About this study
Official title: Phase Ib Study of Tisagenlecleucel in Combination With Pembrolizumab in Relapsed/Refractory (r/r) Diffuse Large B-cell Lymphoma (DLBCL) Patients.
A multi-center, open-label, phase Ib study to evaluate the safety and efficacy of the administration of tisagenlecleucel in combination with pembrolizumab in patients with r/r DLBCL who have received 2 or more lines of systemic therapy, including an anti-CD20 and anthracycline based chemotherapy and having failed to or are not candidates for ASCT. The study will consist of 2 parts: dose timing selection part and expansion part.
- Conditions
- Diffuse Large B-cell Lymphoma
- Being tested
- Tisagenlecleucel, Pembrolizumab
- Keywords
- Lymphoma tisagenlecleucel, Diffuse Large B-cell Lymphoma, CTL019, PORTIA, DLBCL, tisagenlecleucel, pembrolizumab, r/r Diffuse large B-cell Lymphoma, relapsed/refractory Diffuse large B-cell Lymphoma
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TisagenlecleucelBiological
Also called CTL019
Gene modified autologous T cells
PembrolizumabDrug
anti PD-1
| Study group | Role | What they receive |
|---|---|---|
| Tisagenlecleucel+Pembrolizumab | Experimental | Not described Receives: Biological: Tisagenlecleucel; Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent of participants recieving pembrolizumab per protocol schedule
Measured: 21 days after first pembrolizumab infusion
Dose Timing part: Incidence of dose limiting toxicities (DLTs)
Measured: 21 days after first pembrolizumab infusion
Expansion part: Overall response rate (ORR)
Measured: 3 month post tisagenlecleucel infusion
Secondary outcomes (6)
Duration of Response (DOR)
Measured: 24 months
Progression Free Survival (PFS)
Measured: 24 months
Overall Survival (OS)
Measured: 24 months
In vivo cellular kinetics of tisagenlecleucel in blood, bone marrow, lymph nodes and other tissues by qPCR and flow cytometry
Measured: 24 months
Impact of pembrolizumab dosing strategy on the cellular kinetics of tisagenlecleucel by qPCR and flow cytometry
Measured: 24 months
Immunogenicity measured by antibody titres specific to tisagenlecleucel molecule and by the presence of T lymphocytes activated by the tisagenlecleucel protein
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 posted14 Aug 2018
- Study start9 Oct 2018
- Primary completion20 Jul 2021
- Study completion20 Jul 2021
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 Diffuse Large B-cell LymphomaStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03630159
- Sponsor's protocol ID
- CCTL019J2101
- Other IDs
- 2018-000973-57, 2018
- Acronym
- PORTIA
- Status last verified
- Aug 2022
- First submitted
- 1 Aug 2018
- Last updated
- 15 Aug 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Jaeger U, Worel N, McGuirk JP, Riedell PA, Fleury I, Du Y, Han X, Pearson D, Redondo S, Waller EK. Safety and efficacy of tisagenlecleucel plus pembrolizumab in patients with r/r DLBCL: phase 1b PORTIA study results. Blood Adv. 2023 Jun 13;7(11):2283-2286. doi: 10.1182/bloodadvances.2022007779.
PubMed 36044388Ernst 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 34515338
Study at a glance
From the registry record, last updated by the sponsor on 15 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase Ib Study of Tisagenlecleucel in Combination With Pembrolizumab in Relapsed/Refractory (r/r) Diffuse Large B-cell Lymphoma (DLBCL) Patients.
- ClinicalTrials.gov ID
- NCT03630159
- Acronym / sponsor ID
- PORTIA / CCTL019J2101
- Conditions
- Diffuse Large B-cell Lymphoma
- Keywords
- Lymphoma tisagenlecleucel, Diffuse Large B-cell Lymphoma, CTL019, PORTIA, DLBCL, tisagenlecleucel, pembrolizumab, r/r Diffuse large B-cell Lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 9 Oct 2018 (actual)
- Primary completion
- 20 Jul 2021 (actual)
- Study completion
- 20 Jul 2021 (actual)
- First posted
- 14 Aug 2018 (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.
A multi-center, open-label, phase Ib study to evaluate the safety and efficacy of the administration of tisagenlecleucel in combination with pembrolizumab in patients with r/r DLBCL who have received 2 or more lines of systemic therapy, including an anti-CD20 and anthracycline based chemotherapy and having failed to or are not candidates for ASCT. The study will consist of 2 parts: dose timing selection part and expansion part.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tisagenlecleucel+Pembrolizumab | Experimental | Biological: Tisagenlecleucel, Drug: Pembrolizumab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Confirmed DLBCL per local histopathology assessment.
- Relapsed or refractory disease after having recieved 2 or more lines of systemic therapy, including anti-CD20 and anthracycline based chemotherapy, and either having progressed after (or relapsed after) ASCT, or being not candidates for or not consenting to ASCT.
- Measurable disease at time of enrollment
- ECOG performance status that is either 0 or 1 at screening.
Key exclusion criteria (8 listed)
- Patients with Richter's transformation, and Burkitt lymphoma, and primary DLBCL of CNS.
- Prior treatment with any prior anti-CD19/anti-CD3 therapy, or any other anti-CD19 therapy.
- Patients with active CNS involvement are excluded, except if the CNS involvement has been effectively treated and provided that local treatment was >4 weeks before enrollment.
- Prior allogeneic HSCT.
- Unstable angina and/or myocardial infarction and/or coronary artery bypass graft (CABG), or stroke within 6 months prior to screening, and/or impaired cardiac function or clinically significant cardiac disease
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 |
|---|---|---|
| TisagenlecleucelAlso: CTL019Gene modified autologous T cells | Biological | Tisagenlecleucel+Pembrolizumab |
| Pembrolizumabanti PD-1 | Drug | Tisagenlecleucel+Pembrolizumab |
Primary outcome
Percent of participants recieving pembrolizumab per protocol schedule
Time frame: 21 days after first pembrolizumab infusion
Dose Timing part: Incidence of dose limiting toxicities (DLTs)
Time frame: 21 days after first pembrolizumab infusion
Expansion part: Overall response rate (ORR)
Time frame: 3 month post tisagenlecleucel infusion
6 secondary outcomes
Duration of Response (DOR)
Time frame: 24 months
Progression Free Survival (PFS)
Time frame: 24 months
Overall Survival (OS)
Time frame: 24 months
In vivo cellular kinetics of tisagenlecleucel in blood, bone marrow, lymph nodes and other tissues by qPCR and flow cytometry
Time frame: 24 months
Impact of pembrolizumab dosing strategy on the cellular kinetics of tisagenlecleucel by qPCR and flow cytometry
Time frame: 24 months
Immunogenicity measured by antibody titres specific to tisagenlecleucel molecule and by the presence of T lymphocytes activated by the tisagenlecleucel protein
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 15 Aug 2022.
- Derived from this study: PubMed 36044388Jaeger U, Worel N, McGuirk JP, Riedell PA, Fleury I, Du Y, Han X, Pearson D, Redondo S, Waller EK. Safety and efficacy of tisagenlecleucel plus pembrolizumab in patients with r/r DLBCL: phase 1b PORTIA study results. Blood Adv. 2023 Jun 13;7(11):2283-2286. doi: 10.1182/bloodadvances.2022007779.
- 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.
- Novartis results databaseLink provided by the sponsor.
- A Plain Language Trial Summary is available on novctrd.comLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
5 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Tisagenlecleucel and Pembrolizumab in people with Diffuse Large B-cell Lymphoma, run by Novartis Pharmaceuticals at 5 sites in 3 countries.
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 4 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 15 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States, Austria, Canada. 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 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.
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?
Percent of participants recieving pembrolizumab per protocol schedule (time frame: 21 days after first pembrolizumab infusion). The study lists 3 primary outcomes in all. 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 NCT03630159, 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 15 Aug 2022.