Non-Hodgkins Lymphoma (NHL) Patients, With CD19+B Cell LymphomasPhase 2NCT02030834
Phase IIa Study of Redirected Autologous T Cells Engineered to Contain Anti-CD19 Attached to TCRz and 4-Signaling Domains in Patients With Chemotherapy Relapsed or Refractory CD19+ Lymphomas
A Phase 2 study testing CART-19 in people with Non-Hodgkins Lymphoma (NHL) Patients, With CD19+B Cell Lymphomas, run by University of Pennsylvania at 1 site in United States.
Trial summary
Phase IIa study to estimate the efficacy of a single infusion of autologous T cells expressing CD19 chimeric antigen receptors expressing tandem TCR and 4-1BB (TCR /4-1BB) costimulatory domains (referred to as CART-19 or CTL019 cells) in non-Hodgkins Lymphoma (NHL) patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Hodgkins Lymphoma (NHL) Patients, With CD19+B Cell Lymphomas
- What is being tested?
- CART-19
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 63 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Feb 2014to 1 Sep 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Male or female subjects with CD19+ B cell lymphomas with no available curative treatment options (such as autologous or allogeneic SCT) who have a limited prognosis (several months to <2 year survival) with currently available therapies will be enrolled. The study will enroll 51 evaluable subjects as follows:
- CD19+ Lymphoma
- Cohort A Subjects:
- Follicular lymphoma, previously identified as CD19+ i. At least 2 prior chemotherapy or immunochemotherapy regimens (not including single agent monoclonal antibody therapy) ii. Patients who progress within 2 years after second or higher line of therapy will be eligible. For instance, patients who have progression of lymphoma < 2 years after second or greater line therapy, but who have responded to their most recent treatment (3rd line or higher) will be eligible. Patients may have progression, stable disease or responding disease at the time of enrollment.
- Patients with a history of large cell transformation are eligible. b. Mantle cell lymphoma, previously identified as CD19+ i. Beyond 1st CR with relapsed disease, progressive disease during first line rituximab-chemotherapy combination, or persistent disease after first line rituximab-chemotherapy combination and not eligible or appropriate for conventional allogeneic or autologous SCT.
- Relapsed after prior autologous SCT. c. Diffuse large B cell lymphoma, previously identified as CD19+ i. Residual disease after primary therapy and not eligible for autologous SCT ii. Relapsed or persistent disease after prior autologous SCT iii. Beyond 1st CR with relapsed or persistent disease and not eligible or appropriate for conventional allogeneic or autologous SCT iv. Patients with an antecedent history of follicular lymphoma or CLL/SLL are eligible.
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- Cohort B Subjects:
- Diffuse large B cell lymphoma, previously identified as CD19+ CD19 i. Residual disease after primary therapy and not eligible for autologous SCT ii. Relapsed or persistent disease after prior autologous SCT iii. Beyond 1st CR with relapsed or persistent disease and not eligible or appropriate for conventional allogeneic or autologous SCT iv. Patients with an antecedent history of follicular lymphoma or CLL/SLL are eligible.
- Patients with T cell/histiocyte-rich disease as confirmed by surgical pathology report
- Cohort C Subjects:
- Diffuse large B cell lymphoma, previously identified as CD19+ i. Residual disease after primary therapy and not eligible for autologous SCT ii. Relapsed or persistent disease after prior autologous SCT iii. Beyond 1st CR with relapsed or persistent disease and not eligible or appropriate for conventional allogeneic or autologous SCT iv. Patients with an antecedent history of follicular lymphoma or CLL/SLL are eligible.
- Age ≥18 years
- Creatinine < 1.6 mg/dL
- ALT/AST < 3x upper limit of normal
- Bilirubin <2.0 mg/dL, unless subject has Gilbert's Syndrome (<3.0 mg/dL)
- Any relapse after prior autologous SCT will make patient eligible regardless of other prior therapy.
- Patients with relapsed disease after prior allogeneic SCT (myeloablative or non-myeloablative) will be eligible if they meet all other inclusion criteria and:
- Have no active GVHD and require no immunosuppression
- Are more than 6 months from transplant
- Measurable or assessable disease according to the "Revised Response Criteria for Malignant Lymphoma" (Cheson et al., J. Clin. Onc., 1999)108. Patients in complete remission with no evidence of disease are not eligible.
- Performance status (ECOG) 0 or 1.
- Left Ventricle Ejection Fraction (LVEF) > 40% confirmed by ECHO/MUGA
- Written informed consent is given. Successful T cell test expansion (first 10 subjects).
Who cannot join
- Pregnant or lactating women. The safety of this therapy on unborn children is not known. Female study participants of reproductive potential must have a negative serum pregnancy test at enrollment. A urine pregnancy test will be performed within 48 hours before infusion.
- Uncontrolled active infection.
- Active hepatitis B or hepatitis C infection.
- Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary. For additional details regarding use of steroids
- Any uncontrolled active medical disorder that would preclude participation as outlined.
- Class III/IV cardiovascular disability according to the New York Heart Association Classification (see Appendix 1).
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- HIV infection.
- Patients with active CNS involvement by malignancy. Patients with prior CNS disease that has been effectively treated will be eligible providing treatment was >4 weeks before enrollment
- Patients in complete remission with no assessable disease.
- Patients with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system.
Trial locations and contacts
1 site in 1 country.
United States1 site
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Phase IIa study to estimate the efficacy of a single infusion of autologous T cells expressing CD19 chimeric antigen receptors expressing tandem TCR and 4-1BB (TCR /4-1BB) costimulatory domains (referred to as CART-19 or CTL019 cells) in non-Hodgkins Lymphoma (NHL) patients. The duration of active protocol intervention is approximately 24 months from screening visit. The protocol will require approximately 48 months to complete.
- Being tested
- CART-19
- Medical subject headings
- Lymphoma, Non-Hodgkin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CART-19Biological
Single infusion of CART-19 cells administered by i.v. injection (total dose of 1 - 5 x108 CART-19 cells, calculated as a range of 2-50% transduced cells in total cells).
| Study group | Role | What they receive |
|---|---|---|
| Cohort A | Experimental | murine CART19 Receives: Biological: CART-19 |
| Cohort B | Experimental | T cell/histiocyte-rich Diffuse Large B Cell Lymphoma (DLBCL) treated with murine CART19 Receives: Biological: CART-19 |
| Cohort C | Experimental | Diffuse Large B Cell Lymphoma (DLBCL) treated with humanized CART19 Receives: Biological: CART-19 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Subjects With an Overall Response (i.e. Either Complete Response or Partial Response) Evaluated at Three Months Post Infusion.
Responders will include those patients achieving complete response (CR), complete response unconfirmed (CRu) and partial response (PR) using anatomic imaging such as CT or MRI to assess tumor volume or, in the event of bone marrow involvement, morphologic and immunohistochemical confirmation that the bone marrow infiltrate has been cleared.
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2014 (estimated)
- Study start5 Feb 2014
- Primary completion16 Sep 2019
- Study completion1 Sep 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Non-Hodgkins Lymphoma (NHL) Patients, With CD19+B Cell LymphomasStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 63 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Stephen Schuster, MD, Principal investigator, Abramson Cancer Center at Penn Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02030834
- Sponsor's protocol ID
- UPCC 13413, 818607
- Status last verified
- Oct 2020
- First submitted
- 7 Jan 2014
- Last updated
- 22 Jun 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Paruzzo L, Chong ER, Chong EA, Zheng Z, Guruprasad P, Landsburg DJ, Nasta SD, Stella F, Ramasubramanian R, de Souza VB, Alkhatib MH, Ho M, Imparato A, Chen GM, Siegel DL, Plesa G, Dai A, Mackey S, Das P, Michener P, Jadlowsky J, Bushman FD, Patel V, Carturan A, Napier EB, Gonzalez VE, Jarocha D, Xu R, Levine BL, Porazzi P, Frey N, Porter DL, Svoboda J, Fraietta JA, June CH, Schuster SJ, Ruella M. Decade-long persistence of CD19 CAR T cells in B cell lymphomas. Nat Med. 2026 Aug 10. doi: 10.1038/s41591-026-04578-1. Online ahead of print.
PubMed 42575986Ruella M, Paruzzo L, Chong ER, Chong EA, Landsburg DJ, Nasta SD, Devi P, Michener P, Stella F, Carturan A, Napier EB, Van Deerlin VM, Porazzi P, Levine BL, Frey N, Porter DL, Fraietta JA, Svoboda J, June CH, Schuster SJ. Ten-Year Outcomes after CAR T-Cell Therapy for B-Cell Lymphomas. N Engl J Med. 2026 Jun 25;394(24):2440-2448. doi: 10.1056/NEJMoa2518035.
PubMed 42341302Ernst 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 34515338Schuster SJ, Svoboda J, Chong EA, Nasta SD, Mato AR, Anak O, Brogdon JL, Pruteanu-Malinici I, Bhoj V, Landsburg D, Wasik M, Levine BL, Lacey SF, Melenhorst JJ, Porter DL, June CH. Chimeric Antigen Receptor T Cells in Refractory B-Cell Lymphomas. N Engl J Med. 2017 Dec 28;377(26):2545-2554. doi: 10.1056/NEJMoa1708566. Epub 2017 Dec 10.
PubMed 29226764
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase IIa Study of Redirected Autologous T Cells Engineered to Contain Anti-CD19 Attached to TCRz and 4-Signaling Domains in Patients With Chemotherapy Relapsed or Refractory CD19+ Lymphomas
- ClinicalTrials.gov ID
- NCT02030834
- Acronym / sponsor ID
- UPCC 13413, 818607
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 63 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- 5 Feb 2014 (actual)
- Primary completion
- 16 Sep 2019 (actual)
- Study completion
- 1 Sep 2020 (actual)
- First posted
- 9 Jan 2014 (estimated)
- Results
- Posted 5 Oct 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Phase IIa study to estimate the efficacy of a single infusion of autologous T cells expressing CD19 chimeric antigen receptors expressing tandem TCR and 4-1BB (TCR /4-1BB) costimulatory domains (referred to as CART-19 or CTL019 cells) in non-Hodgkins Lymphoma (NHL) patients. The duration of active protocol intervention is approximately 24 months from screening visit. The protocol will require approximately 48 months to complete.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cohort A | Experimental | Biological: CART-19murine CART19 |
| Cohort B | Experimental | Biological: CART-19T cell/histiocyte-rich Diffuse Large B Cell Lymphoma (DLBCL) treated with murine CART19 |
| Cohort C | Experimental | Biological: CART-19Diffuse Large B Cell Lymphoma (DLBCL) treated with humanized CART19 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Male or female subjects with CD19+ B cell lymphomas with no available curative treatment options (such as autologous or allogeneic SCT) who have a limited prognosis (several months to <2 year survival) with currently available therapies will be enrolled. The study will enroll 51 evaluable subjects as follows:
- CD19+ Lymphoma
- Follicular lymphoma, previously identified as CD19+ i. At least 2 prior chemotherapy or immunochemotherapy regimens (not including single agent monoclonal antibody therapy) ii. Patients who progress within 2 years after second or higher line of therapy will be eligible. For instance, patients who have progression of lymphoma < 2 years after second or greater line therapy, but who have responded to their most recent treatment (3rd line or higher) will be eligible. Patients may have progression, stable disease or responding disease at the time of enrollment.
- Patients with a history of large cell transformation are eligible. b. Mantle cell lymphoma, previously identified as CD19+ i. Beyond 1st CR with relapsed disease, progressive disease during first line rituximab-chemotherapy combination, or persistent disease after first line rituximab-chemotherapy combination and not eligible or appropriate for conventional allogeneic or autologous SCT.
- Relapsed after prior autologous SCT. c. Diffuse large B cell lymphoma, previously identified as CD19+ i. Residual disease after primary therapy and not eligible for autologous SCT ii. Relapsed or persistent disease after prior autologous SCT iii. Beyond 1st CR with relapsed or persistent disease and not eligible or appropriate for conventional allogeneic or autologous SCT iv. Patients with an antecedent history of follicular lymphoma or CLL/SLL are eligible.
Key exclusion criteria (10 listed)
- Pregnant or lactating women. The safety of this therapy on unborn children is not known. Female study participants of reproductive potential must have a negative serum pregnancy test at enrollment. A urine pregnancy test will be performed within 48 hours before infusion.
- Uncontrolled active infection.
- Active hepatitis B or hepatitis C infection.
- Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary. For additional details regarding use of steroids
- Any uncontrolled active medical disorder that would preclude participation as outlined.
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 |
|---|---|---|
| CART-19Single infusion of CART-19 cells administered by i.v. injection (total dose of 1 - 5 x108 CART-19 cells, calculated as a range of 2-50% transduced cells in total cells). | Biological | Cohort A, Cohort B, Cohort C |
Primary outcome
Number of Subjects With an Overall Response (i.e. Either Complete Response or Partial Response) Evaluated at Three Months Post Infusion.
Time frame: 3 months
Responders will include those patients achieving complete response (CR), complete response unconfirmed (CRu) and partial response (PR) using anatomic imaging such as CT or MRI to assess tumor volume or, in the event of bone marrow involvement, morphologic and immunohistochemical confirmation that the bone marrow infiltrate has been cleared.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42575986Paruzzo L, Chong ER, Chong EA, Zheng Z, Guruprasad P, Landsburg DJ, Nasta SD, Stella F, Ramasubramanian R, de Souza VB, Alkhatib MH, Ho M, Imparato A, Chen GM, Siegel DL, Plesa G, Dai A, Mackey S, Das P, Michener P, Jadlowsky J, Bushman FD, Patel V, Carturan A, Napier EB, Gonzalez VE, Jarocha D, Xu R, Levine BL, Porazzi P, Frey N, Porter DL, Svoboda J, Fraietta JA, June CH, Schuster SJ, Ruella M. Decade-long persistence of CD19 CAR T cells in B cell lymphomas. Nat Med. 2026 Aug 10. doi: 10.1038/s41591-026-04578-1. Online ahead of print.
- Derived from this study: PubMed 42341302Ruella M, Paruzzo L, Chong ER, Chong EA, Landsburg DJ, Nasta SD, Devi P, Michener P, Stella F, Carturan A, Napier EB, Van Deerlin VM, Porazzi P, Levine BL, Frey N, Porter DL, Fraietta JA, Svoboda J, June CH, Schuster SJ. Ten-Year Outcomes after CAR T-Cell Therapy for B-Cell Lymphomas. N Engl J Med. 2026 Jun 25;394(24):2440-2448. doi: 10.1056/NEJMoa2518035.
- 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 29226764Schuster SJ, Svoboda J, Chong EA, Nasta SD, Mato AR, Anak O, Brogdon JL, Pruteanu-Malinici I, Bhoj V, Landsburg D, Wasik M, Levine BL, Lacey SF, Melenhorst JJ, Porter DL, June CH. Chimeric Antigen Receptor T Cells in Refractory B-Cell Lymphomas. N Engl J Med. 2017 Dec 28;377(26):2545-2554. doi: 10.1056/NEJMoa1708566. Epub 2017 Dec 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.
Stephen Schuster, MD principal investigator
Abramson Cancer Center at Penn Medicine
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 CART-19 in people with Non-Hodgkins Lymphoma (NHL) Patients, With CD19+B Cell Lymphomas, run by University of Pennsylvania at 1 site in United States.
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 23 inclusion and 10 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 22 Jun 2023. 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 United States. 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?
Yes. Results are posted in the registry (first posted 5 Oct 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Subjects With an Overall Response (i.e. Either Complete Response or Partial Response) Evaluated at Three Months Post Infusion. (time frame: 3 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 NCT02030834, which also lists 4 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 22 Jun 2023.