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

NCT07319676 | Recruiting Phase 1

• 1 other identifier: 2022/00272
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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. The study will have the following parts:

• 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.

Conditions

B-cell Lymphoma Refractory

Keywords

Antigen targeted; T cell therapy; Relapsed/Refractory B cell lymphomas

Outcome Measures

Primary Outcomes (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.

  6 months

Study Arms (1)

CAR T-cells

EXPERIMENTAL

The 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.

Other: CART infusion

Interventions

CART infusion OTHER

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.

CAR T-cells

Eligibility Criteria

• Age: 10 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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).
• 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)

Sponsors & Collaborators

• National University Hospital, Singapore: lead

Study Sites (1)

National University Hospital

Singapore, Singapore, 119228, Singapore

RECRUITING

Related Publications (18)

• 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.

  PMID: 24876563 RESULT

• 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.

  PMID: 28925994 RESULT

• 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.

  PMID: 30592986 RESULT

• 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.

  PMID: 31723828 RESULT

• 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.

  PMID: 20660832 RESULT

• 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.

  PMID: 29437609 RESULT

• 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.

  PMID: 30501490 RESULT

• 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.

  PMID: 30518502 RESULT

• 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.

  PMID: 26755709 RESULT

• 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.

  PMID: 32278358 RESULT

• 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.

  PMID: 29155426 RESULT

• 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.

  PMID: 33147337 RESULT

• 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.

  PMID: 31056762 RESULT

• 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.

  PMID: 33512414 RESULT

• 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.

  PMID: 34312556 RESULT

• Cordoba S, Onuoha S, Thomas S, Pignataro DS, Hough R, Ghorashian S, Vora A, Bonney D, Veys P, Rao K, Lucchini G, Chiesa R, Chu J, Clark L, Fung MM, Smith K, Peticone C, Al-Hajj M, Baldan V, Ferrari M, Srivastava S, Jha R, Arce Vargas F, Duffy K, Day W, Virgo P, Wheeler L, Hancock J, Farzaneh F, Domning S, Zhang Y, Khokhar NZ, Peddareddigari VGR, Wynn R, Pule M, Amrolia PJ. CAR T cells with dual targeting of CD19 and CD22 in pediatric and young adult patients with relapsed or refractory B cell acute lymphoblastic leukemia: a phase 1 trial. Nat Med. 2021 Oct;27(10):1797-1805. doi: 10.1038/s41591-021-01497-1. Epub 2021 Oct 12.

  PMID: 34642489 RESULT

• Shalabi H, Kraft IL, Wang HW, Yuan CM, Yates B, Delbrook C, Zimbelman JD, Giller R, Stetler-Stevenson M, Jaffe ES, Lee DW, Shern JF, Fry TJ, Shah NN. Sequential loss of tumor surface antigens following chimeric antigen receptor T-cell therapies in diffuse large B-cell lymphoma. Haematologica. 2018 May;103(5):e215-e218. doi: 10.3324/haematol.2017.183459. Epub 2018 Feb 1. No abstract available.

  PMID: 29419431 RESULT

• Plaks V, Rossi JM, Chou J, Wang L, Poddar S, Han G, Wang Z, Kuang SQ, Chu F, Davis RE, Vega F, Bashir Z, Jacobson CA, Locke FL, Reagan PM, Rodig SJ, Lekakis LJ, Flinn IW, Miklos DB, Bot A, Neelapu SS. CD19 target evasion as a mechanism of relapse in large B-cell lymphoma treated with axicabtagene ciloleucel. Blood. 2021 Sep 23;138(12):1081-1085. doi: 10.1182/blood.2021010930. No abstract available.

  PMID: 34041526 RESULT

MeSH Terms

Conditions

Lymphoma, B-Cell

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Michelle Poon

  NUHS

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Michelle Poon

CONTACT

67724394; michelle_poon@nuhs.edu.sg

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: December 21, 2025
• First Posted: January 6, 2026
• Study Start: March 2, 2026
• Primary Completion (Estimated): October 31, 2028
• Study Completion (Estimated): October 31, 2040
• Last Updated: April 9, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)