P1, N=54, Recruiting, Novartis Pharmaceuticals | Not yet recruiting --> Recruiting | Trial completion date: Nov 2027 --> Jul 2027

P4, N=80, Not yet recruiting, The Third Affiliated Hospital, Sun Yat-sen University; The Third Affiliated Hospital, Sun Yat-sen University

P1, N=48, Recruiting, Century Therapeutics, Inc. | N=30 --> 48

"Introduction: Brexucabtagene autoleucel (brexu cel) is a CD19-targeted chimeric antigen receptor (CAR) T cell therapy approved for the treatment of adults with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL)...No differences were observed with respect to sex, TP53 mutation status, prior inotuzumab (ino) or blinatumomab (blina) exposure, disease burden prior to CAR, or development of any cytokine release syndrome (CRS) or any neurotoxicity with brexu cel... In a large real-world cohort of adults with R/R B-ALL infused with brexu cel, we identified practice variation regarding the use of consolidative HCT. Among brexu cel recipients who entered an MRD- CR, we identified ClonoSeq NGS MRD negativity as a novel predictive factor of favorable oncologic outcomes, even without a consolidative HCT. Similar results have been obtained in pediatric ALL patietns ftreated with 41BB-based tisagenleucleucel (Pulsipher et al., Blood Cancer Discovery 2022)."

P2, N=300, Suspended, National Cancer Institute (NCI) | N=550 --> 300

This report presents two pediatric ALL cases (one Ph+ and one Ph-like) with minimal residual disease negativity established by multicolor flow cytometry but persistent transcript detection by quantitative PCR (qPCR) even after second-line treatment with tyrosine kinase inhibitors combined with blinatumomab immunotherapy. Using droplet digital PCR, BCR::ABL1 or TPM3::PDGFRB transcripts were identified in CD19+ cells as well as in non-CD19+ cells, suggesting the presence of a Ph+ or Ph-like ALL-M subtype originating from hematopoietic stem cells. This report provides information for better characterization, diagnosis, and treatment of these ALL subtypes.

P1, N=209, Recruiting, BioRay Pharmaceutical Co., Ltd. | Not yet recruiting --> Recruiting | Phase classification: P1/2 --> P1

P=N/A, N=30, Not yet recruiting, Institute of Hematology & Blood Diseases Hospital, China

P1, N=33, Recruiting, Imugene Limited | N=52 --> 33 | Trial completion date: Sep 2025 --> May 2029 | Trial primary completion date: Sep 2024 --> Jun 2027

P1, N=10, Not yet recruiting, Amgen

P=N/A, N=36, Not yet recruiting, Shandong University

Two patients did not achieve remission even after two rounds of induction chemotherapy, with one achieving complete remission after treatment with blinatumomab immunotherapy...Five patients died, while two patients survived with sustained complete remission. TCF3-HLF-positive B-ALL is rare and has a high relapse rate and poor prognosis.

P1, N=31, Completed, Amgen | Phase classification: P1b --> P1

P1/2, N=0, Withdrawn, Tenet Medicines | N=40 --> 0 | Not yet recruiting --> Withdrawn

P1, N=28, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2024 --> Jul 2025

P1/2, N=26, Recruiting, Vironexis Biotherapeutics Inc. | Not yet recruiting --> Recruiting

P4, N=10, Terminated, Amgen | N=45 --> 10 | Trial completion date: Dec 2025 --> Sep 2024 | Recruiting --> Terminated | Trial primary completion date: Dec 2025 --> Sep 2024; The decision to terminate is not based on safety or efficacy but due to slow enrollment impacting the ability to complete the study as planned.

P2, N=171, Not yet recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2027 --> Dec 2028 | Initiation date: Oct 2024 --> Jan 2025 | Trial primary completion date: Dec 2027 --> Dec 2028

P3; Initiation date: Jul 2024 --> Feb 2025

P1/2, N=125, Recruiting, Amgen | Trial completion date: Jul 2032 --> Mar 2029 | Trial primary completion date: Feb 2031 --> Oct 2027

P2, N=170, Active, not recruiting, St. Jude Children's Research Hospital | Recruiting --> Active, not recruiting | N=52 --> 170

P2, N=71, Active, not recruiting, The Lymphoma Academic Research Organisation | Recruiting --> Active, not recruiting

P=N/A, N=60, Recruiting, Amgen | Trial completion date: Aug 2032 --> Oct 2032 | Trial primary completion date: Aug 2032 --> Oct 2032

P2, N=190, Recruiting, Zenas BioPharma (USA), LLC | Not yet recruiting --> Recruiting

P=N/A, N=15, Not yet recruiting, Second Affiliated Hospital, School of Medicine, Zhejiang University

P1, N=24, Not yet recruiting, The First Affiliated Hospital with Nanjing Medical University

P1, N=24, Not yet recruiting, Cullinan Therapeutics Inc.

CAR-MNZ bearing the CD28-OX40-CD3ζ signaling modules, and CAR-BG2, designed on the Tisagenlecleucel CAR sequence (Kymriah®), carrying the 4-1BB and CD3ζ signaling elements, were employed. CIK + Blina displayed strongest NFAT and IFN-ɣ induction, whereas CARCIK-BG2 demonstrated superior synapse formation. All the effectors have shown therapeutic activity in vivo against the CD19+ Daudi tumor model, with CARCIK cells showing a more durable response compared to CIK + Blina, likely due to the short half-life of Blina in this model.

P2/3, N=90, Recruiting, Shanghai Jiao Tong University School of Medicine

P1, N=6, Recruiting, The Children's Hospital of Zhejiang University School of Medicine

P=N/A, N=0, Available, Amgen

Can chemotherapy-free approaches, such as blinatumomab in conjunction with more potent TKIs, obviate the need for an allograft in high-risk patients?...Can salvage therapy and a subsequent allograft cure patients who relapse after not being transplanted in CR1? This manuscript reviews the latest data influencing contemporary management and discusses these controversies.

P=N/A, N=50, Recruiting, Xuanwu Hospital, Beijing | Not yet recruiting --> Recruiting

P4, N=128, Recruiting, West China Hospital,Sichuan University; West China Hospital,Sichuan University

P1/2, N=20, Recruiting, Sichuan Baili Pharmaceutical Co., Ltd. | Trial completion date: Aug 2024 --> Dec 2024 | Trial primary completion date: Aug 2024 --> Dec 2024

P1/2, N=40, Recruiting, Sichuan Baili Pharmaceutical Co., Ltd. | Trial completion date: Aug 2024 --> Dec 2024 | Trial primary completion date: Aug 2024 --> Dec 2024

She was treated with modified Ph-negative EWALL induction (Vincristine, Idarubicin, dexamethasone) and achieved a complete remission. However, she subsequently experienced an early relapse and was refractory to targeted therapy with blinatumomab. After treatment with inotuzumab ozogamicin, she achieved a second complete remission...It demonstrates that patients with ostensibly favourable prognostic factors may experience poor response rates to traditional chemotherapy as well as targeted salvage agents. It also illustrates the challenges of treating B-ALL in the elderly population.

P2, N=25, Recruiting, Incyte Corporation | Initiation date: Jun 2024 --> Nov 2022

P1, N=20, Recruiting, OHSU Knight Cancer Institute | Trial completion date: Jun 2026 --> Dec 2026 | Trial primary completion date: Jun 2025 --> Dec 2025

P3, N=1005, Recruiting, AstraZeneca | Not yet recruiting --> Recruiting

Blinatumomab was associated with greater benefit in terms of OS and EFS relative to SC. Probabilistic, deterministic, and scenario analyses indicate that blinatumomab represents the best value for money. Therefore, blinatumomab administered as part of consolidation therapy in B-ALL pediatric patients with high-risk first relapse is a cost-effective option.

Significant progress has been made in recent years in the treatment of adults with Philadelphia chromosome-positive (Ph-positive) acute lymphoblastic leukemia (ALL).1 Combining BCR::ABL1 tyrosine kinase inhibitors (TKIs) with intensive chemotherapy regimens like hyper-fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate and cytarabine (hyper-CVAD) and others has greatly improved patient outcomes.2 As a result, allogeneic hematopoietic stem cell transplantation (HSCT) has become an additional valuable option...Specifically, the 5-year PFS rates were 81% with hyper-CVAD plus ponatinib, 54% with hyper-CVAD plus dasatinib, and 64% with hyper-CVAD plus imatinib...In contrast to the D-ALBA trial, only two patients underwent HSCT.26 Whether the combination of blinatumomab and ponatinib can overcome the poor prognosis of IKZF1plus and the negative impact of an elevated white blood cell count (higher than 70×109/L, as shown in a multivariate analysis to correlate with a higher risk of relapse) remains to be determined.Asciminib is a first-in-class selective allosteric ABL myristoyl pocket (STAMP) inhibitor that was evaluated in combination with dasatinib and prednisone in a phase 1 trial of 25 patients with Ph-positive ALL, with a median age of 65 years (range, 33 to 85 years).27 Fourteen patients were enrolled in the dose-escalation cohort and 11 in the dose-expansion cohort...Eighteen patients with newly diagnosed Ph-positive ALL received dasatinib/vincristine/prednisone followed by sequential infusions of CD19 and CD22 CAR T cells...The chemotherapy-free regimens involving TKIs alongside blinatumomab have demonstrated outstanding outcomes in the frontline setting, particularly with the utilization of ponatinib. The combination of ponatinib and blinatumomab exhibits high efficacy, with CMR rates of 83% by PCR and 98% by ClonoSEQ and a 3-year OS rate of 91%, with only two patients undergoing HSCT.