huCART19

P1, N=20, Not yet recruiting, National Institute of Allergy and Infectious Diseases (NIAID) | Initiation date: Mar 2024 --> May 2024

P1/2, N=93, Recruiting, Stephan Grupp MD PhD | Trial completion date: Jan 2026 --> Jan 2029 | Trial primary completion date: Jan 2025 --> Jan 2027

P1/2, N=89, Recruiting, Stephan Grupp MD PhD | Trial completion date: Sep 2027 --> Sep 2029 | Trial primary completion date: Sep 2025 --> Sep 2027

P1/2, N=89, Recruiting, Stephan Grupp MD PhD | Active, not recruiting --> Recruiting | Trial primary completion date: Sep 2023 --> Sep 2025

P1/2, N=89, Active, not recruiting, Stephan Grupp MD PhD | Recruiting --> Active, not recruiting

P2, N=100, Active, not recruiting, University of Pennsylvania | Recruiting --> Active, not recruiting | N=63 --> 100

P1/2, N=93, Recruiting, Stephan Grupp MD PhD | Not yet recruiting --> Recruiting

The extracellular domain that we will use corresponds to the mouse monoclonal antibody that recognizes human CD19 from tisagenlecleucel®. It is feasible to develop a huCART-19 with research grade in Mexico, the next step is to evaluate its function in a clinical model.

P1/2, N=93, Not yet recruiting, Stephan Grupp MD PhD

We conducted a phase 1 clinical trial of anti-BCMA CAR T cells (CART-BCMA) with or without anti-CD19 CAR T cells (huCART19) in multiple myeloma (MM) patients responding to third- or later- line therapy (Phase A, N=10) or high-risk patients responding to first-line therapy (Phase B, N=20), followed by early lenalidomide or pomalidomide maintenance. Outcomes with CART-BCMA + huCART19 were similar to CART-BCMA alone. Collectively, our results demonstrate favorable safety, pharmacokinetics, and antimyeloma activity of dual-target CAR T cell therapy in early lines of multiple myeloma treatment.

P1/2, N=89, Recruiting, Stephan Grupp MD PhD | Not yet recruiting --> Recruiting

P1/2, N=89, Not yet recruiting, Stephan Grupp MD PhD

P2, N=63, Recruiting, University of Pennsylvania | Trial completion date: Aug 2022 --> Aug 2024 | Trial primary completion date: Aug 2022 --> Aug 2024

CTL019/huCART19/tisagenlecleucel are effective at achieving durable remissions across cytogenetic categories. Relapsed/refractory patients with high-risk cytogenetics, including KMT2A-rearranged infant ALL, demonstrated high RFS and OS probabilities at 2 years.

Methods : Adult patients with r/r ALL were co-administered two humanized autologous CAR T cell products, one targeted to CD19 (huCART19) and the other to CD22 (CART22-65s) after fludarabine and cyclophosphamide lymphodepletion... Of 13 treated patients (median age 46 (range 28-71)), two had received prior murine CART19 cells, 8 had prior blinatumomab, 8 had prior inotuzumab and 10 had a prior allogeneic stem cell transplant (SCT)...This syndrome was refractory to IL6 and IL1beta inhibition but ultimately responded to ruxolitinib... Co-administration and adaptive dosing of CART22-65s with huCART19 in adult patients with r/r ALL is feasible and effective. The two different products demonstrated differential expansion and persistence kinetics. Despite prior exposure to CD19- and/or CD22-specific immunotherapies, all evaluable patients achieved CR with uMRD; we continue to monitor CAR T cell persistence and its impact on durability of response.

Reinfusion of CTL019/tisagenlecleucel or huCART19 is safe, may prolong B-cell aplasia in patients with short CAR persistence and reduce relapse risk, and can induce remissions in patients with CD19+ relapsed disease. Thus, reinfusion may provide an alternative to HSCT for short persistence. However, reinfusion is not effective for patients with nonresponse to initial CAR infusion.

Tisagenlecleucel and huCART19 are active at clearing CNS disease and maintaining durable remissions in children and young adults with CNS relapsed or refractory B-cell acute lymphocytic leukaemia or lymphocytic lymphoma, without increasing the risk of severe neurotoxicity; although care should be taken in the timing of therapy and disease control to mitigate this risk. These preliminary findings support the use of these CAR T-cell therapies for patients with CNS relapsed or refractory B-cell acute lymphocytic leukaemia.

P1, N=81, Completed, University of Pennsylvania | Active, not recruiting --> Completed | Trial completion date: Nov 2022 --> Sep 2021

P2, N=63, Recruiting, University of Pennsylvania | Trial primary completion date: Aug 2021 --> Aug 2022

P1, N=40, Active, not recruiting, University of Pennsylvania | Trial primary completion date: May 2022 --> Mar 2036

P1, N=23, Active, not recruiting, University of Pennsylvania | Trial completion date: Sep 2037 --> Jan 2036

P2, N=63, Recruiting, University of Pennsylvania | Active, not recruiting --> Recruiting

HuCART19 achieved durable remissions with long-term persistence in children and young adults with relapsed or refractory B-ALL, including after failure of prior CAR T-cell therapy.

P2, N=63, Active, not recruiting, University of Pennsylvania | Recruiting --> Active, not recruiting

P1, N=40, Active, not recruiting, University of Pennsylvania | Trial primary completion date: May 2021 --> May 2022

P1, N=12, Not yet recruiting, Abramson Cancer Center of the University of Pennsylvania | Initiation date: Nov 2020 --> Apr 2021

P2, N=85, Recruiting, University of Pennsylvania | Trial completion date: Aug 2021 --> Aug 2022 | Trial primary completion date: Jan 2021 --> Aug 2021

P1, N=23, Active, not recruiting, University of Pennsylvania | Recruiting --> Active, not recruiting

P1, N=18, Recruiting, University of Pennsylvania | Trial completion date: Sep 2033 --> Sep 2037 | Trial primary completion date: Jan 2021 --> Jan 2036

P1, N=12, Not yet recruiting, Abramson Cancer Center of the University of Pennsylvania | Initiation date: Jul 2020 --> Nov 2020