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B-cell Lymphoma RefractoryPhase 1/2NCT07319676

Antigen Targeted T Cell Therapy for Relapsed/Refractory B Cell Lymphomas

A Phase 1/2 study testing CART infusion in people with B-cell Lymphoma Refractory, run by National University Hospital, Singapore at 1 site in Singapore.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

This is a single center, open label, phase 1 lead in to determine Recommended Phase 2 Dose (RP2D), followed by a phase 2 trial to evaluate the safety and efficacy of Epo-R-CD19 CAR T with or without CD22 CAR T-cells infused into patients with B cell lymphoma. Read more about this study

Who is it for?
Ages 10 to 80 years
Conditions the study is for
B-cell Lymphoma Refractory
What is being tested?
CART infusion
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
1 siteSingapore
Study dates
2 Mar 2026to 31 Oct 2040
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

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 10 to 80 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Age 10 to 80 years at screening
  • PET-CT measurable disease by Lugano classification (Deauville score of ≥4) and
  • Tissue biopsy of any tumour site and flow cytometry study of CD19 and CD22 expression.
  • Relapsed B-cell lymphoma after one line of systemic therapy or autologous bone marrow transplant. This includes DLBCL, PMBCL, HGBCL, DLBCL arising from indolent lymphoma, Burkitt's lymphoma/leukemia, Mantle cell lymphoma.
  • High risk B-cell lymphoma (BCL). High risk BCL is defined by any of the criteria below:
  • High-risk genetics - double/triple hit or p53mut or deletion.
Show all 12Show fewer
  • IPI score ≥ 3
  • Richter's transformation from chronic lymphocytic leukaemia.
  • Disease refractory to treatment - PET-CT positive disease after 2 courses of rituximab-containing chemoimmunotherapy.
  • PBMC product available
  • Karnofsky or Lansky score >70. Or ECOG 0-2
  • Patient expected survival is more than 3 months to allow for manufacture and release of CAR T-cells.

Who cannot join

  • Patients who test positive on urine or blood pregnancy testing and are pregnant or are lactating.
  • Participant of reproducible age who refuse the use of the following birth control methods if engaging in sexual activity that could lead to pregnancy. The methods include condoms, diaphragm, intrauterine device, hormonal based contraception.
  • Concomitant genetic syndromes associated with BM failure states, such as Fanconi anaemia, Kostmann syndrome, Schwachman syndrome, or any other BM failure syndrome with the exception of Down syndrome.
  • Active hepatitis B or hepatitis C within 3 months of screening.
  • Active HIV infection within 3 months of screening.
  • Grade 2 to 4 graft-vs-host disease (GVHD).
Show all 11Show fewer
  • Received an investigational medicinal product within 1 month of screening.
  • If the total sum of CD19 and CD22 antigens expressed is less than 95.0%, patients will not be eligible. If subsequent immunophenotying of the patient's sample confirms that total sum of CD19 and CD22 antigens ≥ 95%, the patient may be rescreened.
  • Central nervous system: Uncontrolled seizures or status epilepticus; decreased conscious state (any cause)
  • Foreign patients who cannot commit to agreeable to stay in Singapore for at least 3 months post CAR T infusion and are committed to the long term monitoring post CAR T at home and in Singapore.
  • Prior treatment with any CAR T cell therapy (approved or investigational)

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Michelle Poon contact

67724394

michelle_poon@nuhs.edu.sg

Singapore1 site, 1 recruiting

  • National University Hospital

    Singapore, Singapore, 119228

    Michelle Poon, MBBS, MRCP, (65) 6908 2222

    Michelle Poon, MBBS, MRCP

    Recruiting

Other trials in Singapore

About this study

This is a single center, open label, phase 1 lead in to determine Recommended Phase 2 Dose (RP2D), followed by a phase 2 trial to evaluate the safety and efficacy of Epo-R-CD19 CAR T with or without CD22 CAR T-cells infused into patients with B cell lymphoma.

The study will have the following parts:

Read more
  • Screening
  • Pre-infusion (cell product preparation and bridging) and infusion (lymphodepletion)
  • Primary efficacy endpoints
  • Long term follow up

Patients who have high risk B cell lymphoma or relapsed/refractory B cell lymphoma who fufil the trial inclusion and exclusion criteria will undergo leukapheresis following trial enrollment.

CAR T-cell products will then be manufactured according to the antigen expression on the patient's biopsied tumor cells. These cells will then undergo stringent testing before the patient undergoes lymphodepletion followed by CART infusion. These patients will be admitted for the infusion and closely monitored for any CRS or ICANS.

This study will have a Phase 1 safety run in for the first 3-6 patients who receive the Epo-R-CD19 CAR T (with or without epoetin (erythropoietin)) to determine the tolerability and safety of this product. For the first 3-6 patients, if there are any DLT seen by Day 28, a data safety monitoring committee will be convened to assess the trial. Staggered dosing will be implemented for the first 2 participants in every dose level (DL1, DL2 and DL-1).

For Phase 2, the RP2D will depend on DLT. If there is no DLT at DL+1 and DL+2, then the investigators will proceed with DL+2 as the RP2D dose. On the other hand, if there is DLT despite DL-1, then the study will be redesigned. Phase 2 will continue until a total of 20 patients received their CAR T-cell infusions.

CAR-T monitoring will be performed at Day 0, 7, 14, 21, 28, month 2, 3, 4, 5, 6, 12 and yearly thereafter. The total duration of the study is 15 years from CAR T infusion.

Read the detailed description

2.1 Hypothesis

  1. The infusion of CD19 with or without CD 22 targeted CAR T-cells in patients with high risk or R/R BCL will improve the overall response rates and survival outcomes. The choice of antigen target is determined by detailed flow cytometric profiling of biopsied lymphoma cells if possible.
  2. The co-expression of Epo-R in our CD19 CAR T-cells will allow endogenous or exogenous Epo levels to support survival and expansion of infused T cells, thus overcoming the issue of suboptimal T-cell expansion and persistence due to prior chemotherapies in patients with high risk or R/R DLBCL.

2.2 Objectives for Phase 1:

Primary objective of Phase 1 lead in is to determine safety, as defined by incidence of dose limiting toxicities (DLT) associated to the Epo-R-CD19 CAR and CD22 pooled products, as well as determination of the RP2D of the Epo-R-CD19

The secondary objective is to assess efficacy of the Epo-R-CD19 CAR as defined by:

  1. Percentage of patients who achieve peak CAR T level within Month 1 > 30 CD 19 CAR-T cells/uL ii) Proportion of patients who achieved no evidence of disease as determined PET-CT using the Lugano criteria at 1 month and the best overall response by 6 months as assessed by PET-CT (Lugano criteria).

2.3 Objectives For Phase 2:

The primary objective of Phase 2 is efficacy. The primary endpoints are:

  1. To determine the efficacy of a single Epo-R-CD19 CAR T-cell or a pool of CAR T-cells targeting CD19 and CD22 antigens based on detailed flow cytometric profiling of high risk or R/R BCL patients. The efficacy is determined by the proportion of patients who achieved no evidence of disease as determined PET-CT using the Lugano criteria at 1 month and the best overall response by 6 months as assessed by PET-CT (Lugano criteria).

Our secondary endpoints are:

  1. To determine the safety of the Epo-R-CD19 and CD22. The investigators will collect data on CAR T related toxicities: This includes incidence of dose limiting toxicities (Section 5), treatment related adverse events (Section Table 4.9) and adverse events of special interest (Section 2.5).
  2. To determine the peripheral blood levels of CAR CD19 and CD22 at D0, D5, D7, D14, D21 and 1 month, 3 months, 6 months, 1 year and 2 years. The investigators will compare our Epo-R-CD19 CAR T-cell levels against CD22 and published commercial CAR T expansion.
  3. To study the 1-year Event free survival defined by any event involving disease recurrence or persistence disease at 6 months, death from any cause. Planned HSCT, after CAR T infusion, is not an event
  4. To study the 1-year Overall Survival
  5. Cumulative risk of relapse (CIR), defined as proportion of patients surviving 1-year after CAR T-cell infusion.
Being tested
CART infusion
Keywords
Antigen targeted, T cell therapy, Relapsed/Refractory B cell lymphomas
Medical subject headings
Lymphoma, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CART infusionOther

    CART cells originate with the isolation of the patient's T cells via apheresis. These cells are then activated and modified to express a transgene that encodes a tumor-specific CAR. These cells are then expanded to achieve a clinically significant cell dose which will then be infused back into the patient. After CART infusion, these CART cells will come into contact with the tumor-specific antigen on the surface of the tumor cells, activating the CART cells which will expand and kill the tumor cells.

Study groups in NCT07319676
Study groupRoleWhat they receive
CAR T-cellsExperimentalThe CAR T-cells used in this clinical trial are autologous T cells that have been cultured ex vivo and transduced with a retroviral vector delivering a gene encoding a CAR, as described in the accompanying Chemistry, Manufacturing and Controls (CMC) document. Each infusion bag will have affixed to it a label containing the following: product identifier, product name and volume. In addition, the label will also have at least 2 unique identifiers such as name of patient, patient's alphanumeric identifier and birth date, according to applicable regulations. Prior to infusion, 2 individuals will verify all information and confirm the identity to ensure that the information is correctly matched to the patient and that the patient receives only their autologous product. This is done according to local institutional guidelines.
Receives: Other: CART infusion

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Best objective response post CAR-T infusion

    Best objective response will be assessed using standardised lymphoma response criteria at regular intervals up to 6 months post CAR-T infusion.

    Measured: 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Jan 2026
  2. Study start2 Mar 2026
  3. Primary completion31 Oct 2028 (estimated)
  4. Study completion31 Oct 2040 (estimated)

Resources

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
Sequential
Model description
This study will start with the phase 1 lead in to determine the R2PF followed by a phase 2 trial to evaluate the safety and efficacy of Epo-R-CD19 CAR T with or without CD22 CAR T-cells infused into patients with BCL.
Masking
None (open label)
Enrolment
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07319676
Sponsor's protocol ID
2022/00272
Status last verified
Mar 2026
First submitted
21 Dec 2025
Last updated
9 Apr 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Lee DW, Gardner R, Porter DL, Louis CU, Ahmed N, Jensen M, Grupp SA, Mackall CL. Current concepts in the diagnosis and management of cytokine release syndrome. Blood. 2014 Jul 10;124(2):188-95. doi: 10.1182/blood-2014-05-552729. Epub 2014 May 29.

    PubMed 24876563

  • Neelapu SS, Tummala S, Kebriaei P, Wierda W, Gutierrez C, Locke FL, Komanduri KV, Lin Y, Jain N, Daver N, Westin J, Gulbis AM, Loghin ME, de Groot JF, Adkins S, Davis SE, Rezvani K, Hwu P, Shpall EJ. Chimeric antigen receptor T-cell therapy - assessment and management of toxicities. Nat Rev Clin Oncol. 2018 Jan;15(1):47-62. doi: 10.1038/nrclinonc.2017.148. Epub 2017 Sep 19.

    PubMed 28925994

  • Lee DW, Santomasso BD, Locke FL, Ghobadi A, Turtle CJ, Brudno JN, Maus MV, Park JH, Mead E, Pavletic S, Go WY, Eldjerou L, Gardner RA, Frey N, Curran KJ, Peggs K, Pasquini M, DiPersio JF, van den Brink MRM, Komanduri KV, Grupp SA, Neelapu SS. ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells. Biol Blood Marrow Transplant. 2019 Apr;25(4):625-638. doi: 10.1016/j.bbmt.2018.12.758. Epub 2018 Dec 25.

    PubMed 30592986

  • Garcia Borrega J, Godel P, Ruger MA, Onur OA, Shimabukuro-Vornhagen A, Kochanek M, Boll B. In the Eye of the Storm: Immune-mediated Toxicities Associated With CAR-T Cell Therapy. Hemasphere. 2019 Mar 29;3(2):e191. doi: 10.1097/HS9.0000000000000191. eCollection 2019 Apr.

    PubMed 31723828

  • Gisselbrecht C, Glass B, Mounier N, Singh Gill D, Linch DC, Trneny M, Bosly A, Ketterer N, Shpilberg O, Hagberg H, Ma D, Briere J, Moskowitz CH, Schmitz N. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol. 2010 Sep 20;28(27):4184-90. doi: 10.1200/JCO.2010.28.1618. Epub 2010 Jul 26.

    PubMed 20660832

  • Crump M, Neelapu SS, Farooq U, et al. Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study. Blood. 2017;130(16):1800-1808. Blood. 2018 Feb 1;131(5):587-588. doi: 10.1182/blood-2017-11-817775. No abstract available.

    PubMed 29437609

  • Schuster SJ, Bishop MR, Tam CS, Waller EK, Borchmann P, McGuirk JP, Jager U, Jaglowski S, Andreadis C, Westin JR, Fleury I, Bachanova V, Foley SR, Ho PJ, Mielke S, Magenau JM, Holte H, Pantano S, Pacaud LB, Awasthi R, Chu J, Anak O, Salles G, Maziarz RT; JULIET Investigators. Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma. N Engl J Med. 2019 Jan 3;380(1):45-56. doi: 10.1056/NEJMoa1804980. Epub 2018 Dec 1.

    PubMed 30501490

  • Locke FL, Ghobadi A, Jacobson CA, Miklos DB, Lekakis LJ, Oluwole OO, Lin Y, Braunschweig I, Hill BT, Timmerman JM, Deol A, Reagan PM, Stiff P, Flinn IW, Farooq U, Goy A, McSweeney PA, Munoz J, Siddiqi T, Chavez JC, Herrera AF, Bartlett NL, Wiezorek JS, Navale L, Xue A, Jiang Y, Bot A, Rossi JM, Kim JJ, Go WY, Neelapu SS. Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1-2 trial. Lancet Oncol. 2019 Jan;20(1):31-42. doi: 10.1016/S1470-2045(18)30864-7. Epub 2018 Dec 2.

    PubMed 30518502

  • Viardot A, Goebeler ME, Hess G, Neumann S, Pfreundschuh M, Adrian N, Zettl F, Libicher M, Sayehli C, Stieglmaier J, Zhang A, Nagorsen D, Bargou RC. Phase 2 study of the bispecific T-cell engager (BiTE) antibody blinatumomab in relapsed/refractory diffuse large B-cell lymphoma. Blood. 2016 Mar 17;127(11):1410-6. doi: 10.1182/blood-2015-06-651380. Epub 2016 Jan 11.

    PubMed 26755709

  • Stirrups R. CAR T-cell therapy for relapsed or refractory mantle-cell lymphoma. Lancet Oncol. 2020 May;21(5):e239. doi: 10.1016/S1470-2045(20)30231-X. Epub 2020 Apr 9. No abstract available.

    PubMed 32278358

  • Fry TJ, Shah NN, Orentas RJ, Stetler-Stevenson M, Yuan CM, Ramakrishna S, Wolters P, Martin S, Delbrook C, Yates B, Shalabi H, Fountaine TJ, Shern JF, Majzner RG, Stroncek DF, Sabatino M, Feng Y, Dimitrov DS, Zhang L, Nguyen S, Qin H, Dropulic B, Lee DW, Mackall CL. CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy. Nat Med. 2018 Jan;24(1):20-28. doi: 10.1038/nm.4441. Epub 2017 Nov 20.

    PubMed 29155426

  • Pasquini MC, Hu ZH, Curran K, Laetsch T, Locke F, Rouce R, Pulsipher MA, Phillips CL, Keating A, Frigault MJ, Salzberg D, Jaglowski S, Sasine JP, Rosenthal J, Ghosh M, Landsburg D, Margossian S, Martin PL, Kamdar MK, Hematti P, Nikiforow S, Turtle C, Perales MA, Steinert P, Horowitz MM, Moskop A, Pacaud L, Yi L, Chawla R, Bleickardt E, Grupp S. Real-world evidence of tisagenlecleucel for pediatric acute lymphoblastic leukemia and non-Hodgkin lymphoma. Blood Adv. 2020 Nov 10;4(21):5414-5424. doi: 10.1182/bloodadvances.2020003092.

    PubMed 33147337

  • Chow VA, Gopal AK, Maloney DG, Turtle CJ, Smith SD, Ujjani CS, Shadman M, Cassaday RD, Till BG, Tseng YD, Warren EH, Shustov AR, Menon MP, Bhark S, Acharya UH, Mullane E, Hannan LM, Voutsinas JM, Gooley TA, Lynch RC. Outcomes of patients with large B-cell lymphomas and progressive disease following CD19-specific CAR T-cell therapy. Am J Hematol. 2019 Aug;94(8):E209-E213. doi: 10.1002/ajh.25505. Epub 2019 May 21. No abstract available.

    PubMed 31056762

  • Baird JH, Frank MJ, Craig J, Patel S, Spiegel JY, Sahaf B, Oak JS, Younes SF, Ozawa MG, Yang E, Natkunam Y, Tamaresis J, Ehlinger Z, Reynolds WD, Arai S, Johnston L, Lowsky R, Meyer E, Negrin RS, Rezvani AR, Shiraz P, Sidana S, Weng WK, Davis KL, Ramakrishna S, Schultz L, Mullins C, Jacob A, Kirsch I, Feldman SA, Mackall CL, Miklos DB, Muffly L. CD22-directed CAR T-cell therapy induces complete remissions in CD19-directed CAR-refractory large B-cell lymphoma. Blood. 2021 Apr 29;137(17):2321-2325. doi: 10.1182/blood.2020009432.

    PubMed 33512414

  • Spiegel JY, Patel S, Muffly L, Hossain NM, Oak J, Baird JH, Frank MJ, Shiraz P, Sahaf B, Craig J, Iglesias M, Younes S, Natkunam Y, Ozawa MG, Yang E, Tamaresis J, Chinnasamy H, Ehlinger Z, Reynolds W, Lynn R, Rotiroti MC, Gkitsas N, Arai S, Johnston L, Lowsky R, Majzner RG, Meyer E, Negrin RS, Rezvani AR, Sidana S, Shizuru J, Weng WK, Mullins C, Jacob A, Kirsch I, Bazzano M, Zhou J, Mackay S, Bornheimer SJ, Schultz L, Ramakrishna S, Davis KL, Kong KA, Shah NN, Qin H, Fry T, Feldman S, Mackall CL, Miklos DB. CAR T cells with dual targeting of CD19 and CD22 in adult patients with recurrent or refractory B cell malignancies: a phase 1 trial. Nat Med. 2021 Aug;27(8):1419-1431. doi: 10.1038/s41591-021-01436-0. Epub 2021 Jul 26.

    PubMed 34312556

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing CART infusion in people with B-cell Lymphoma Refractory, run by National University Hospital, Singapore at 1 site in Singapore.

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 12 inclusion and 11 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: looking for participants now, as of the sponsor's last update on 9 Apr 2026. 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 Singapore. 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?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Michelle Poon (67724394, michelle_poon@nuhs.edu.sg), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Best objective response post CAR-T infusion (time frame: 6 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 NCT07319676, which also lists 18 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 9 Apr 2026.

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