Phase I Safety and Tolerability Trial of CD19 Directed CAR T Cells in Adult Patients with B-Cell Acute Lymphoblastic Leukemia (B-ALL) with Minimal Residual Disease (MRD) Positivity At First Complete Remission

This open-label, single arm Phase I trial aims to determine the safety and tolerability of anti-CD19 chimeric antigen receptor-expressing (CAR) T cells (UCD19 CAR T) in adults B-ALL that are in first complete remission with minimal residual disease (MRD) positivity. This trial will enroll 10 patients for apheresis and treatment with lymphodepleting chemotherapy followed by UCD19 CAR T cell infusion. Patients will be assessed for dose limiting toxicities (DLTs) (within 42 days after CAR T infusion), duration of B cell aplasia, overall response rate (at 1-, 3-, 6- and 12-months), and overall survival and event free survival (at 12- and 24- months) post UCD19 CAR T infusion.

开始日期2024-01-24

申办/合作机构

University of Colorado Denver

NCT04544592 / Recruiting临床1/2期IIT

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)

This phase I/II trial will investigate a new CD19 directed CAR-T therapy manufactured locally with the goals to expedite infusion to wider patient inclusion that includes those who were previously excluded, such as pediatric patients with B-cell NHL and patients in primary relapse.

开始日期2021-02-24

申办/合作机构

University of Colorado Denver

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100 项与 CD19 Directed CAR T Cells(University of Colorado Denver) 相关的转化医学

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项与 CD19 Directed CAR T Cells(University of Colorado Denver) 相关的文献（医药）

2024-07-15·Journal of Clinical Investigation

CAR+ extracellular vesicles predict ICANS in patients with B cell lymphomas treated with CD19-directed CAR T cells

Article

作者: Cavallo, Carola ; Asioli, Gian Maria ; Garagnani, Paolo ; Ricci, Francesca ; Zinzani, Pier Luigi ; Kwiatkowska, Katarzyna Malgorzata ; Maffini, Enrico ; Bonifazi, Francesca ; Pirazzini, Chiara ; Casadei, Beatrice ; Messelodi, Daria ; Dan, Elisa ; Iannotta, Francesco ; Sinigaglia, Barbara ; Vaglio, Francesca ; Bonafè, Massimiliano ; Arpinati, Mario ; Laprovitera, Noemi ; Ferracin, Manuela ; De Felice, Francesco ; Ursi, Margherita ; Naddeo, Maria ; Bertuccio, Salvatore Nicola ; Carella, Matteo ; Barbato, Francesco ; Storci, Gianluca ; Tazzari, Pier Luigi ; Cortelli, Pietro ; Tomassini, Enrica ; De Matteis, Serena ; Guarino, Maria ; Tassoni, Marta ; Rossini, Lucrezia ; Pellegrini, Cinzia ; Severi, Caterina ; Santi, Spartaco ; Guadagnuolo, Serafina ; Dicataldo, Michele ; Roberto, Marcello

BACKGROUNDPredicting immune effector cell-associated neurotoxicity syndrome (ICANS) in patients infused with CAR T cells is still a conundrum. This complication, thought to be consequent to CAR T cell activation, arises a few days after infusion, when circulating CAR T cells are scarce and specific CAR T cell-derived biomarkers are lacking.METHODSCAR+ extracellular vesicle (CAR+EV) release was assessed in human CD19.CAR T cells cocultured with CD19+ target cells. A prospective cohort of 100 patients with B cell lymphoma infused with approved CD19.CAR T cell products was assessed for plasma CAR+EVs as biomarkers of in vivo CD19.CAR T cell activation. Human induced pluripotent stem cell-derived (iPSC-derived) neural cells were used as a model for CAR+EV-induced neurotoxicity.RESULTSIn vitro release of CAR+EVs occurs within 1 hour after target engagement. Plasma CAR+EVs are detectable 1 hour after infusion. A concentration greater than 132.8 CAR+EVs/μL at hour +1 or greater than 224.5 CAR+EVs/μL at day +1 predicted ICANS in advance of 4 days, with a sensitivity and a specificity outperforming other ICANS predictors. ENO2+ nanoparticles were released by iPSC-derived neural cells upon CAR+EV exposure and were increased in plasma of patients with ICANS.CONCLUSIONPlasma CAR+EVs are an immediate signal of CD19.CAR T cell activation, are suitable predictors of neurotoxicity, and may be involved in ICANS pathogenesis.TRIAL REGISTRATIONNCT04892433, NCT05807789.FUNDINGLife Science Hub-Advanced Therapies (financed by Health Ministry as part of the National Plan for Complementary Investments to the National Recovery and Resilience Plan [NRRP]: E.3 Innovative health ecosystem for APC fees and immunomonitoring).

Annals of Hematology

CAR-T cells for the treatment of pediatric chronic myeloid leukemia in repeatedly relapsed lymphoid blast phase

Article

作者: Lion, Thomas ; Metzler, Markus ; Sembill, Stephanie ; Heydrich-Karsten, Christiane ; Chitadze, Guranda ; Suttorp, Meinolf ; Karow, Axel ; Cario, Gunnar ; Kramp, Laura-Jane

AbstractChronic myeloid leukemia presenting de novo in the blast phase (CML-BP) is a rare diagnosis among pediatric malignancies. We report on a 16-year-old male who presented with CML-BP lymphoid at diagnosis. He was treated with shortened acute lymphoblastic leukemia induction plus the tyrosine kinase inhibitor (TKI) imatinib followed by dasatinib. After achieving molecular remission (MR), hematopoietic stem cell transplantation (HSCT) was performed early after diagnosis. Despite prophylactic dasatinib, he relapsed 3 months later with the kinase domain mutation T315I. Multiple therapeutic approaches including ponatinib, blinatumomab, a 2nd HSCT from a different donor, donor lymphocyte infusions, and high-dose asciminib all resulted in subsequent relapse. Another molecular response was achieved by combining ponatinib plus asciminib with chemotherapy. In this situation, CD19-directed CAR-T cells (Kymriah®) were administered for compassionate use and tolerated without adverse events. Compared to all prior therapies, CAR T-cells maintained remission. After 12 months of follow-up, complete B-cell aplasia and low numbers of CAR-T cells are detectable in the peripheral blood, potentially mediating long-term disease control.

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
B细胞淋巴瘤	临床2期	美国	University of Colorado Denver	2021-02-24
CD19阳性B细胞急性淋巴细胞白血病	临床2期	美国	University of Colorado Denver	2021-02-24
前体B细胞急性淋巴细胞白血病	临床2期	美国	University of Colorado Denver	2021-02-24
复发性 B 细胞急性淋巴细胞白血病	临床2期	美国	University of Colorado Denver	2021-02-24
伯基特淋巴瘤	临床1期	美国	University of Colorado Denver	2024-01-24
残留肿瘤	临床1期	美国	University of Colorado Denver	2024-01-24