The promising results seen in the treatment of refractory hematologic malignancies with tisagenlecleucel (Kymriah), the pioneering Chimeric Antigen Receptor (CAR) T-cell immunotherapy, has stimulated a fast growth in research and clinical testing of novel CAR-T constructs, targets, and various generations of CAR T-cells. Pharmacists may receive inquiries about active clinical trials or may be contributing to the care of patients participating in these studies. This briefing discusses the on-going clinical trials that explore novel CAR T-cell immunotherapies in pediatric refractory malignancies of hematologic and solid organ origins. It can be valuable in assisting practitioners in navigating the rapidly evolving field of CAR T-cell immunotherapies.
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MaudeSLLaetschTWBuechnerJ, et al.Tisangenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N Engl J Med. 2018;378:439-448. doi:10.1056/NEJMoa1709866
6.
Seattle Children’s Hospital. Pediatric and Young Adult Leukemia Adoptive Therapy (PLAT)-04: A Phase 1 Feasibility and Safety Study of CD22-CAR T Cell Immunotherapy for CD22+ Leukemia and Lymphoma. ClinicalTrials.gov identifier: NCT03244306; 2023.
7.
Baylor College of Medicine. Glypican 3-specific Chimeric Antigen Receptor Expressed in Autologous T-Cells as Immunotherapy for Patients with Pediatric Solid Tumors. ClinicalTrials.gov identifier: NCT02932956; 2023.
8.
MajznerRGTheruvathJLNellanA, et al.CAR T-cells targeting B7-H3, a pan-cancer antigen, demonstrate potent preclinical activity against pediatric solid tumors and brain tumors. Clin Cancer Res. 2019;25:2560-2574. doi:10.1158/1078-0432.CCR-18-0432
9.
Federal Research Institute of Pediatric Hematology, Oncology and Immunology. Clinical efficacy of the 2nd generation CD19 autologous CAR T-cells on the CliniMACS prodigy automated manufacturing platform in treatment of pediatric and young adult patients with relapsed/refractory B-lineage acute lymphoblastic leukemia. ClinicalTrials.gov identifier: NCT03467256; 2023.
10.
DushenkovAJungsuwadeeP. Chimeric antigen receptor T-cell therapy: Foundational science and clinical knowledge for pharmacy practice. J Oncol Pharm Pract. 2019;25:1217-1225. doi:10.1177/1078155219836480
11.
Tessa Therapeutics. A phase 2 Multi-center study evaluating the safety and Efficacy of CD30-directed genetically Modified autologous T-cells (CD30 CAR-T) in adult and pediatric patients with relapsed or refractory Classical Hodgkin lymphoma. ClinicalTrials.gov identifier: NCT04268706; 2023.
12.
University of Pennsylvania. Phase 1 study of lentivirally transduced T cells engineered to contain anti-CD123 linked to TCRζ and 4-1BB signaling domains in pediatric subjects with refractory or relapsed acute myeloid leukemia. ClinicalTrials.gov identifier: NCT04678336; 2023.
13.
Seattle Children’s Hospital. Pediatric and Young Adult Leukemia Adoptive Therapy (PLAT)-06: A Phase 1/2 Study of CD19-specific CAR T Cells With a Fully Human Binding Domain for CD19+ Leukemia or Lymphoma. ClinicalTrials.gov identifier: NCT03684889; 2023.
14.
Bambino Gesù Hospital and Research Institute. Phase I/II study of anti-CD19 chimeric antigen receptor-expressing T-cells in pediatric patients affected by relapsed/refractory CD19+ acute lymphoblastic leukemia and non-hodgkin lymphoma. ClinicalTrials.gov identifier: NCT03373071; 2022.
15.
Seattle Children’s Hospital. Pediatric and Young Adult Leukemia Adoptive Therapy (PLAT)-05: A Phase 1 Feasibility and Safety Study of Dual Specificity CD19 and CD22 CAR-T Cell Immunotherapy for CD19+CD22+ Leukemia. ClinicalTrials.gov identifier: NCT03330691; 2023.
16.
Seattle Children’s Hospital. Pediatric and Young Adult Leukemia Adoptive Therapy (PLAT)-03: A Pilot Feasibility and Safety Study of CD19t T-Antigen Presenting Cells (T-APCs) Following CAR T Cell Immunotherapy for CD19+ Leukemia. ClinicalTrials.gov identifier: NCT03186118; 2023.
17.
National Cancer Institute (NCI). Phase I Dose Escalation Study of Anti-CD22 Chimeric Receptor T-Cells in Pediatric and Young Adults with Recurrent or Refractory CD22-Expressing B Cell Malignancies. ClinicalTrials.Gov Identifier: NCT02315612; 2024.
18.
Seattle Children’s Hospital. Pediatric and Young Adult Leukemia Adoptive Therapy (PLAT)-02: A Phase 1/2 Feasibility and Safety Study of CD19-CAR T Cell Immunotherapy for CD19+ Leukemia. ClinicalTrials.gov identifier: NCT02028455; 2023.
19.
Seattle Children’s Hospital. Pediatric Leukemia Adoptive Therapy (PLAT)-01: A Phase 1 Feasibility and Safety Study of Cellular Immunotherapy for Relapsed Pediatric CD19+ Acute Lymphoblastic Leukemia Using Autologous T-cells Lentivirally Transduced To Express a CD19-Specific Chimeric Antigen Receptor. ClinicalTrials.gov identifier: NCT01683279; 2023.
20.
Seoul National University Hospital. Treatment of CD19 Chimeric antigen receptor T-cells for pediatric patients with CD19-positive B-cell acute lymphoblastic leukemia who are Indicated for hematopoietic stem cell Transplantation. ClinicalTrials.gov identifier: NCT06247501; 2024.
21.
Autolus Limited. A Single-Arm, Open-label, Multi-Centre, phase Ib study evaluating the safety and Preliminary Efficacy of AUTO1 in pediatric patients with CD19-positive relapsed/refractory B cell acute lymphoblastic leukemia and Aggressive Mature B cell non-Hodgkin lymphoma. ClinicalTrials.gov identifier: NCT06173518; 2023.
22.
Baylor College of Medicine. Phase I. Study of activated T-cells expressing second or third generation CD19-specific Chimeric antigen Receptors for advanced B-cell non-Hodgkin’s lymphoma, acute lymphocytic leukemia and Chronic lymphocytic leukemia (SAGAN). ClinicalTrials.gov identifier: NCT01853631; 2023.
23.
National Cancer Institute (NCI). Phase 1/2 Dose Escalation Study of CD19/CD22 Bicistronic Chimeric Antigen Receptor (CAR) T-Cells in Children and Young Adults with Recurrent or Refractory CD19/CD22-Expressing B Cell Malignancies. ClinicalTrials.Gov Identifier: NCT05442515; 2024.
24.
St. Jude Children’s Research Hospital. A Phase I Study Evaluating Allogeneic Memory T-Cells Engineered to Express Chimeric Antigen Receptors Specific for CD19 for the Treatment of Pediatric and Young Adult Patients ≤ 21 Years of Age with Relapsed or Refractory CD19-Positive Leukemia. ClinicalTrials.Gov Identifier: NCT04881240; 2024.
25.
Children’s Hospital of Philadelphia. Phase 1/2b trial of autologous Humanized CD19-directed Chimeric antigen receptor T-cells manufactured using the CliniMACS Prodigy Platform for the treatment of pediatric B cell acute lymphoblastic leukemia. ClinicalTrials.gov identifier: NCT05480449; 2023.
26.
Bambino Gesù Hospital and Research Institute. Phase I II study of anti-CD19 chimeric antigen receptor-expressing T-cells in pediatric patients affected by relapsed/refractory CD19+ acute lymphoblastic leukemia and diffuse large B cell lymphoma (DLBCL) or primary mediastinal B cell lymphoma (PML). ClinicalTrials. Gov Identifier: NCT04787263; 2021.
27.
University of Colorado, Denver. Phase 1/2 dose escalation and preliminary efficacy of CD19 directed CAR T-cells generated using the miltenyi clinimacs prodigy system (UCD19 CarT) in pediatric patients with relapsed and/or refractory B-cell acute lymphoblastic leukemia (B-ALL) and B-cell non-Hodgkins lymphoma (B-NHL). ClinicalTrials.gov identifier: NCT04544592; 2023.
28.
Belarusian Research Center for Pediatric Oncology, Hematology and Immunology. Pilot study of CD19 CAR T-cells therapy for relapsed or refractory acute lymphoblastic leukemia/lymphoma in children/young adults. ClinicalTrials.gov identifier: NCT05333302; 2023.
29.
Medical College of Wisconsin. Phase 1 study of Redirected autologous T-cells engineered to contain an anti-CD19 and anti-CD20 scFv coupled to CD3ζ and 4-1BB signaling domains in pediatric and young adult patients with relapsed/refractory CD19 or CD20 B-cell acute lymphoblastic leukemia. ClinicalTrials.gov identifier: NCT04049383; 2023.
30.
Seattle Children’s Hospital. Pediatric and Young Adult Leukemia Adoptive Therapy (PLAT)-07: A Phase 1/2 Study of CD22-Specific CAR T Cells for CD22+ Leukemia or Lymphoma. ClinicalTrials.gov identifier: NCT04571138; 2023.
31.
Beijing Boren Hospital. Phase II study of autologous murine anti-CD19 chimeric antigen receptor T-cells treating refractory or relapsed B acute lymphoblastic leukemia children. ClinicalTrials.gov identifier: NCT04325841; 2022.
32.
Children’s Hospital of Fudan University. A Single Center Single arm exploratory clinical study of CD19-directed allogeneic chimeric antigen receptor CAR T-cell immunotherapy cell therapy in pediatric patients with relapsed/refractory B-cell acute lymphoblastic leukemia. ClinicalTrial.gov identifier: NCT04173988; 2022.
33.
UNC Lineberger Comprehensive Cancer Center. Phase ib/II study of the administration of T lymphocytes expressing the CD30 chimeric antigen receptor (CAR) for relapsed/refractory CD30+ hodgkin’s lymphoma and CD30+ non-hodgkin’s lymphoma. ClinicialTrials.gov identifier: NCT02690545; 2023.
34.
Baylor College of Medicine. Autologous Activated T-Cells Transduced with A 3rd Generation GD-2 Chimeric Antigen Receptor and iCaspase9 Safety Switch Administered to Patients with Relapsed or Refractory Neuroblastoma (GRAIN). ClinicalTrials.Gov Identifier: NCT01822652; 2024.
35.
Bambino Gesù Hospital and Research Institute. Phase I Clinical trial on the Use of Fresh, allogeneic, second-generation CD19-CAR T-cells for treatment of children with relapsed/refractory B-cell acute lymphoblastic leukemia. ClinicalTrials.gov identifier: NCT06080191; 2023.
36.
Bambino Gesù Hospital and Research Institute. Phase I/II Study of Anti-CD7 Chimeric Antigen Receptor-Expressing T-Cells in Pediatric Patients Affected by Relapsed/Refractory CD7+ T-Cell Acute Lymphoblastic Leukemia/Lymphoma. ClinicalTrials.Gov Identifier: NCT06064903; 2023.
37.
Hospital Israelita Albert Einstein. A Phase I Clinical Trial Using Genetically Engineered Autologous T-Cells to Express Chimeric Antigen Receptor (CAR) for Treatment of Patients with Refractory or Relapsed CD19-Positive B Lymphoid Malignancies. ClinicalTrials.Gov Identifier: NCT05705570; 2023.
38.
Sabz Biomedicals. Phase I Clinical trial evaluating safety of CD19 CAR T-cells in patients with relapsed or refractory acute B-cell lymphoblastic leukemia (R/R B-ALL). ClinicalTrials.gov identifier: NCT04653493; 2021.
39.
Pediatric Brain Tumor Consortium. Phase 1 Trial of Autologous HER2-specific CAR T Cells in Pediatric Patients with Refractory or Recurrent Ependymoma. ClinicalTrials.Gov Identifier: NCT04903080; 2024.
40.
Seattle Children’s Hospital. Phase 1 Study of EGFR806-specific CAR T-Cell Locoregional Immunotherapy for EGFR-Positive Recurrent or Refractory Pediatric Central Nervous System Tumors. ClinicalTrials.Gov Identifier: NCT03638167; 2023.
41.
Seattle Children’s Hospital. Phase 1 Study of HER2-specific CAR T-Cell Locoregional Immunotherapy for HER2 Positive Recurrent/Refractory Pediatric Central Nervous System Tumors. ClinicalTrials.gov identifier: NCT03500991; 2023.
42.
St. Jude Children’s Research Hospital. Loc3CAR. Locoregional Delivery of B7-H3-specific Chimeric Antigen Receptor Autologous T Cells for Pediatric Patients With Primary CNS Tumors. ClinicalTrials.gov identifier: NCT05835687; 2023.
43.
Instituto de Investigación Hospital Universitario La Paz. A phase I trial of Memory T-cells expressing an NKG2D Chimeric antigen receptor in children, Adolescents and young adults with advanced Sarcoma. ClinicalTrials.gov identifier: NCT06087341; 2023.
44.
Bambino Gesù Hospital and Research Institute. Phase I Study of Anti-GD2 Chimeric Antigen Receptor-Expressing T-Cells in Pediatric and Young Adult Patients Affected by Relapsed/Refractory Central Nervous System Tumors. ClinicalTrials.Gov Identifier: NCT05298995; 2023.
45.
Seattle Children’s Hospital. Phase 1 study of B7-H3-specific CAR T-cell locoregional immunotherapy for diffuse intrinsic pontine glioma/diffuse midline glioma and recurrent or refractory pediatric central nervous system tumors. ClinicalTrials.gov identifier: NCT04185038; 2023.
46.
Seattle Children’s Hospital. Phase I Study of B7H3 CAR T-cell immunotherapy for recurrent/refractory solid tumors in children and young adults. ClinicalTrials.gov identifier: NCT04483778; 2023.
47.
Seattle Children’s Hospital. A phase 1 feasibility and safety study of cellular immunotherapy for Recurrent/refractory neuroblastoma using autologous T-cells Lentivirally transduced to express CD171-specific Chimeric antigen Receptors. ClinicalTrials.gov identifier: NCT02311621; 2023.
48.
Phase I Study of Anti-GD2 Chimeric Antigen Receptor-Expressing T-Cells in Pediatric and Young Adult Patients Affected by Relapsed/Refractory Central Nervous System Tumors. ClinicalTrials.gov identifier: NCT05298995. Updated January 31, 2023. AccessedFebruary 18, 2024.
49.
St. Jude Children’s Research Hospital. B7-H3-Specific Chimeric Antigen Receptor Autologous T-Cell Therapy for Pediatric Patients with Solid Tumors (3CAR). ClinicalTrials.gov identifier: NCT04897321; 2023.
50.
Seattle Children’s Hospital. A phase I feasibility and safety study of Fluorescein-specific (FITC-Ew) CAR T-cells in combination with Parenterally administered Folate-Fluorescein (UB-TT170) for Osteogenic Sarcoma. ClinicalTrials.gov identifier: NCT05312411; 2023.
51.
Baylor College of Medicine. Interleukin-15 Armored Glypican-3-specific Chimeric Antigen Receptor Expressing Autologous T-Cells as Immunotherapy for Children with Solid Tumors. ClinicalTrials.Gov Identifier: NCT04377932; 2023.
52.
Seattle Children’s Hospital. Phase I Study of EGFR806 CAR T-cell immunotherapy for Recurrent/refractory solid tumors in children and young adults. ClinicalTrials.gov identifier: NCT03618381; 2023.
53.
UNC Lineberger Comprehensive Cancer Center. A phase I study of autologous activated T-cells expressing a 2nd generation GD2 chimeric antigen receptor, IL-15, and iCaspase9 safety switch administered to patients with relapsed/refractory neuroblastoma or relapsed/refractory osteosarcoma. ClinicalTrials.gov identifier: NCT03721068; 2023.
54.
Baylor College of Medicine. Interleukin-15 and -21 Armored Glypican-3-specific Chimeric Antigen Receptor Expressing Autologous T-Cells as an Immunotherapy for Children with Solid Tumors (CARE). ClinicalTrials.Gov Identifier: NCT04715191; 2024.
55.
Beam Therapeutics Inc. A Phase 1/2, Dose-Exploration and Dose-Expansion Study Evaluating the Safety and Efficacy of Multiplex Base-Edited, Allogeneic Anti-CD7 CAR-T Cells (BEAM-201) in Relapsed/Refractory T-Cell Acute Lymphoblastic Leukemia (T-ALL) or T-Cell Lymphoblastic Lymphoma (T-LL). ClinicalTrials.Gov Identifier: NCT05885464; 2024.
56.
RafiqSHackettCSBrentjensRJ. Engineering Strategies to Overcome the current Roadblocks in CAR-T cell therapy. Nat Rev Clin Oncol. 2020;17:147-167. doi:10.1038/s41571-019-0297-y
57.
GardnerRFinneyOAnnesleyC, et al.Intent-to-treat leukemia remission by CD19 CAR T cells of defined formulation and dose in children and young adults. Blood. 2017;129(25):3322-3331. doi:10.1182/blood-2017-02-769208
58.
JohnsonAJWeiJRosserJMet al.Rationally Designed Transgene-Encoded cell-surface Polypeptide Tag for Multiplexed Programming of CAR T-cell Synthetic Outputs. Cancer Immunol Res. 2021;9(9):1047-1060. doi:10.1158/2326-6066.CIR-20-0470
59.
VitanzaNARonsleyRChoeM, et al.Locoregional CAR T cells for children with CNS tumors: clinical procedure and catheter safety. Neoplasia. 2023;36:100870. doi:10.1016/j.neo.2022.100870
60.
AlabanzaLPeguesMGeldresC, et al.Function of novel anti-CD19 chimeric antigen receptors with human variable regions is affected by hinge and transmembrane domains. Mol Ther. 2017;25(11):2452-2465. doi:10.1016/j.ymthe.2017.07.013
61.
Novartis Pharmaceuticals. A Phase II, Single Arm, Multicenter Trial to Determine the Efficacy and Safety of CTL019 in Pediatric Patients With Relapsed and Refractory B-cell Acute Lymphoblastic Leukemia. ClinicalTrials.gov identifier: NCT02228096; 2020.
