CD19/CD22 Chimeric Antigen Receptor (CAR) T Cells in Children and Young Adults With Recurrent or Refractory CD19/CD22-expressing B Cell Malignancies

Summary

Background: B-cell leukemias and lymphomas are cancers that are often difficult to treat. The primary objective of this study is to determine the ability to take a patient's own cells (T lymphocytes) and grow them in the laboratory with the cluster of differentiation 19 (CD19/cluster of differentiation 22-chimeric antigen receptor (CD22-CAR) gene through a process called 'lentiviral transduction (also considered gene therapy) and growing them to large numbers to use as a treatment for hematologic cancers in children and young adults.. Researchers want to see if giving modified CD19/CD22-CAR T cells to people with these cancers can attack cancer cells. In addition, the safety of giving these gene modified cells to humans will be tested at different cell doses. Additional objectives are to determine if this therapy can cause regression of B cell cancers and to measure if the gene modified cells survive in patients' blood. Objective: To study the safety and effects of giving CD19/CD22-CAR T cells to children and young adults with B-cell cancer. Eligibility: People ages 3-39 with certain cancers that have not been cured by standard therapy. Their cancer tissue must express the CD19 protein. Design: A sample of participants blood or bone marrow will be sent to National Institutes of Health (NIH) and tested for leukemia. Participants will be screened with: Medical history Physical exam Urine and blood tests (including for human immunodeficiency virus (HIV) Heart and eye tests Neurologic assessment and symptom checklist. Scans, bone marrow biopsy, and/or spinal tap Some participants will have lung tests. Participants will repeat these tests throughout the study and follow-up. Participants will have leukapheresis. Blood will be drawn from a plastic tube (intravenous (IV) or needle in one arm then go through a machine that removes lymphocytes. The remaining blood will be returned to the participant's other arm. Participants will stay in the hospital about 2 weeks. There they will get: Two chemotherapy drugs by IV Their changed cells by IV Standard drugs for side effects Participants will have frequent follow-up visits for 1 year, then 5 visits for the next 4 years. Then they will answer questions and have blood tests every year for 15 years. ...

Timeline

Start

2018-03-26

Primary completion

2024-07-10

Completion

2025-01-13

Publications

• Silbert SK, Gava F, Yates B, Rankin AW, Rocco JM, Shao L, Dreyzin A, Cai Y, Lamplugh C, Han KL, Prochazkova M, Little L, Foley T, Sankaran H, Martin K, Garces P, Jin P, Chien CD, Taylor N, Fry TJ, Yuan CM, Wang HW, Stroncek DF, Highfill SL, Shalabi H, Shah NN. CD19/CD22 bivalent CAR T cells in children, adolescents and young adults with B-ALL: final phase 1 trial results. J Immunother Cancer. 2026 Jun 5;14(6):e015296. doi: 10.1136/jitc-2026-015296.
• Silbert SK, Madan S, Holland EM, Steinberg SM, Little L, Foley T, Epstein M, Sarkisian A, Lee DW, Nikitina E, Kakumanu S, Ruppin E, Shalabi H, Yates B, Shah NN. A comprehensive analysis of adverse events in the first 30 days of phase 1 pediatric CAR T-cell trials. Blood Adv. 2023 Sep 26;7(18):5566-5578. doi: 10.1182/bloodadvances.2023009789.
• Shalabi H, Qin H, Su A, Yates B, Wolters PL, Steinberg SM, Ligon JA, Silbert S, DeDe K, Benzaoui M, Goldberg S, Achar S, Schneider D, Shahani SA, Little L, Foley T, Molina JC, Panch S, Mackall CL, Lee DW, Chien CD, Pouzolles M, Ahlman M, Yuan CM, Wang HW, Wang Y, Inglefield J, Toledo-Tamula MA, Martin S, Highfill SL, Altan-Bonnet G, Stroncek D, Fry TJ, Taylor N, Shah NN. CD19/22 CAR T cells in children and young adults with B-ALL: phase 1 results and development of a novel bicistronic CAR. Blood. 2022 Aug 4;140(5):451-463. doi: 10.1182/blood.2022015795.
• Singh N. Modified T cells as therapeutic agents. Hematology Am Soc Hematol Educ Program. 2021 Dec 10;2021(1):296-302. doi: 10.1182/hematology.2021000262.
• Molina JC, Steinberg SM, Yates B, Lee DW, Little L, Mackall CL, Shalabi H, Shah NN. Factors Impacting Overall and Event-Free Survival following Post-Chimeric Antigen Receptor T Cell Consolidative Hematopoietic Stem Cell Transplantation. Transplant Cell Ther. 2022 Jan;28(1):31.e1-31.e9. doi: 10.1016/j.jtct.2021.10.011. Epub 2021 Oct 20.

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