Kidrolase (L-asparaginase) / Jazz, Merck (MSD) - LARVOL DELTA

AALL1331: Blinatumomab in Treating Younger Patients With Relapsed B-cell Acute Lymphoblastic Leukemia (clinicaltrials.gov) - P3 | N=669 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Sep 2025 ➔ Sep 2026

Trial completion date • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology

Response-Based Chemotherapy in Treating Newly Diagnosed Acute Myeloid Leukemia or Myelodysplastic Syndrome in Younger Patients With Down Syndrome (clinicaltrials.gov) - P3 | N=280 | Active, not recruiting | Sponsor: Children's Oncology Group | Trial completion date: Jul 2025 ➔ Jun 2026

Trial completion date • Acute Myelogenous Leukemia • Developmental Disorders • Genetic Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Oncology • GATA1

Biochemical and Biophysical Divergences between Two Escherichia coli l-Asparaginase II Variants: Potential for Using EcA2-K12 as a Biosimilar. (PubMed, Biochemistry) - "The first FDA-approved EcA2 biopharmaceutical, Elspar, was introduced in 1978, followed by other biosimilars...Our data indicate that EcA2-K12 has lower activity due to the higher conformational dynamics of the N-terminal active site loop. Nevertheless, EcA2-K12 is a beneficial alternative or complement to existing therapeutic schemes with EcA2-4M, due to its higher specificity to l-asparagine, which is of fundamental importance since activity on l-glutamine is associated with harmful side effects."

Journal • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

NCCN has published updates to the following NCCN Harmonized Guidelines for Sub-Saharan Africa: Pediatric Acute Lymphoblastic Leukemia, Version 1.2025 (NCCN)

NCCN guideline • Childhood B Acute Lymphoblastic Leukemia

AALL1331: Blinatumomab in Treating Younger Patients With Relapsed B-cell Acute Lymphoblastic Leukemia (clinicaltrials.gov) - P3 | N=669 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Sep 2024 ➔ Sep 2025

Trial completion date • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology

AALL0631: Combination Chemotherapy With or Without Lestaurtinib in Treating Younger Patients With Newly Diagnosed Acute Lymphoblastic Leukemia (clinicaltrials.gov) - P3 | N=218 | Completed | Sponsor: Children's Oncology Group | Active, not recruiting ➔ Completed

Trial completion • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia

Response-Based Chemotherapy in Treating Newly Diagnosed Acute Myeloid Leukemia or Myelodysplastic Syndrome in Younger Patients With Down Syndrome (clinicaltrials.gov) - P3 | N=280 | Active, not recruiting | Sponsor: Children's Oncology Group | Trial completion date: Jun 2024 ➔ Jul 2025

Trial completion date • Acute Myelogenous Leukemia • Developmental Disorders • Genetic Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Oncology • GATA1

AALL0434: Combination Chemotherapy in Treating Young Patients With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia or T-cell Lymphoblastic Lymphoma (clinicaltrials.gov) - P3 | N=1895 | Active, not recruiting | Sponsor: National Cancer Institute (NCI)

Trial completion date • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Acute Lymphoblastic Leukemia • CD2 • CD20 • CD22 • CD34 • CD5 • CD7 • CD8 • MPO

A Study to Compare Standard Chemotherapy to Therapy With CPX-351 and/or Gilteritinib for Patients With Newly Diagnosed AML With or Without FLT3 Mutations (clinicaltrials.gov) - P3 | N=1400 | Active, not recruiting | Sponsor: Children's Oncology Group | Recruiting ➔ Active, not recruiting

Enrollment closed • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3

AALL1331: Blinatumomab in Treating Younger Patients With Relapsed B-cell Acute Lymphoblastic Leukemia (clinicaltrials.gov) - P3 | N=669 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Apr 2024 ➔ Sep 2024

Trial completion date • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology

AALL0631: Combination Chemotherapy With or Without Lestaurtinib in Treating Younger Patients With Newly Diagnosed Acute Lymphoblastic Leukemia (clinicaltrials.gov) - P3 | N=218 | Active, not recruiting | Sponsor: Children's Oncology Group | Trial completion date: Jul 2023 ➔ Jun 2024

Trial completion date • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • FLT3

Our Experiences with Asparaginase Activity Measurements in Children with Lymphoblastic Diseases. (PubMed, Children (Basel)) - "Monitoring of AEA can help to identify patients with 'silent inactivation' and their asparaginase therapy can thus be optimized."

Journal • Hematological Disorders • Oncology • Pediatrics

AALL1331: Blinatumomab in Treating Younger Patients With Relapsed B-cell Acute Lymphoblastic Leukemia (clinicaltrials.gov) - P3 | N=669 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Jun 2023 ➔ Apr 2024

Trial completion date • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology

AALL1331: Blinatumomab in Treating Younger Patients With Relapsed B-cell Acute Lymphoblastic Leukemia (clinicaltrials.gov) - P3 | N=669 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Dec 2030 ➔ Jun 2023

Trial completion date • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology

"ALL-T: how do you use Spectrila, same scheme as Kidrolase or less?#spectrila # ALL-T @AaronGoodman33 @smbenlazar @nihardesai7 @melmehdi" (@rabiihouda)

A Targeted Catalytic Nanobody (T-CAN) with Asparaginolytic Activity (EACR 2022) - "The T-CAN fusion protein also retains ASNase activity (4.30±0.26 U/mg), can bind CD19 and show increased cytotoxic activity on CD19 positive B-ALL cell lines compared to the full-length Kidrolase (percentage of live cells at 0.3 U/mL: 21.42±3.60% vs. 35.47±3.40% for REH, respectively, and 76.66±5.10% vs. 89.02±4.51% for RAJI cells). Conclusion sdASNase and T-CAN represent a strong proof-of-concept for further engineering of new, unexplored platforms for the transfer and targeting of ASNase activity and provide the basis for the formulation of ASNase-based drugs with reduced side effects and improved efficacy."

Hematological Malignancies • Leukemia • Oncology • Pancreatitis • T Acute Lymphoblastic Leukemia

Response-Based Chemotherapy in Treating Newly Diagnosed Acute Myeloid Leukemia or Myelodysplastic Syndrome in Younger Patients With Down Syndrome (clinicaltrials.gov) - P3 | N=312 | Active, not recruiting | Sponsor: Children's Oncology Group | Recruiting ➔ Active, not recruiting

Enrollment closed • Acute Myelogenous Leukemia • Developmental Disorders • Genetic Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Oncology • GATA1

AALL1331: Blinatumomab in Treating Younger Patients With Relapsed B-cell Acute Lymphoblastic Leukemia (clinicaltrials.gov) - P3 | N=670 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Jun 2022 ➔ Dec 2030

Trial completion date • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology

Response-Based Chemotherapy in Treating Newly Diagnosed Acute Myeloid Leukemia or Myelodysplastic Syndrome in Younger Patients With Down Syndrome (clinicaltrials.gov) - P3 | N=312 | Recruiting | Sponsor: Children's Oncology Group | Trial primary completion date: Jun 2023 ➔ Sep 2025

Trial primary completion date • Acute Myelogenous Leukemia • Developmental Disorders • Genetic Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Oncology • GATA1

The Alternative RelB NF-kB Subunit Exerts a Critical Survival Function upon Metabolic Stress in Diffuse Large B-Cell Lymphoma-Derived Cells. (PubMed, Biomedicines) - "Accordingly, RelB inhibition reduce DLBCL mitochondrial ATP production, and sensitizes DLBCL cells to apoptosis induced by Metformin and L-asparaginase (Kidrolase), two FDA approved antimetabolic drugs targeting mitochondrial metabolism. RelB also confers DLBCL cell resistance to glutamine deprivation, an essential amino acid that feeds the TCA cycle. Taken together, our findings uncover a new role for RelB in the regulation of DLBCL cell metabolism and DLBCL cell survival upon metabolic stress."

Journal • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Ultrahigh-Resolution NMR with Water Signal Suppression for a Deeper Understanding of the Action of Antimetabolic Drugs on Diffuse Large B-Cell Lymphoma. (PubMed, J Proteome Res) - "The statistical analyses carried out on the resulting metabolic profiles allow us to successfully highlight several metabolic pathways affected by these drugs. Notably, we show that Kidrolase plays a major role in the metabolic pathways of this DLBCL cell line."

Journal • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

ANTIMETABOLIC COOPERATIVITY WITH THE CLINICALLY-APPROVED L-ASPARAGINASE AND TYROSINE KINASE INHIBITORS TO ERADICATE CML STEM CELLS. (PubMed, Mol Metab) - "We investigated metabolic pathways responsible for CML surviving Imatinib exposure and its potential therapeutic utility to improve the efficiency of TKI against CML stem cells. The combination of TKI with L-asparaginase reactivated the intinsic apoptotic pathway leading to efficient CML cell death. Thus, targeting glutamine metabolism with the clinically-approved drug Kidrolase, in combination with TKI which suppresses glycolysis, represents an effective and widely applicable therapeutic strategy for eradicating CML stem cells."

Clinical • Journal • Chronic Myeloid Leukemia • CNS Disorders • Hematological Malignancies • Leukemia • Oncology • Psychiatry • ABL1 • BCR • CD34

Blinatumomab in Treating Younger Patients With Relapsed B-cell Acute Lymphoblastic Leukemia (clinicaltrials.gov) - P3; N=670; Active, not recruiting; Sponsor: National Cancer Institute (NCI); Trial primary completion date: Dec 2022 ➔ Jun 2021

Trial primary completion date • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology

[VIRTUAL] THROMBOPHILIA AS RISK FACTOR FOR ASPARAGINASE RELATED VENOUS THROMBOEMBOLISM IN PEDIATRIC AND YOUNG ADULT PATIENTS AFFECTED BY ACUTE LYMPHOBLASTIC LEUKEMIA (EHA 2021) - "The types of drugs used were: the native form derived from E. Coli (Medac® and Kidrolase®); the form derived from Erwinia Chrysanthemi (Erwinase®); and the pegylated E. coli ASP (PEG-ASP -Oncaspar®). Conclusion Although thrombophilia is a well-known risk factor for VTE in ALL, our study focused on its link with ASP-related VTE. We suggests that screening for thrombophilia should be performed in ALL patients before ASP administration, since thrombophilic ALL patients may benefit from VTE prophylaxis."

Clinical • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Cardiovascular • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Pediatrics • Respiratory Diseases • Retinal Vein Occlusion • Venous Thromboembolism • MRI

Combination Chemotherapy in Treating Young Patients With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia or T-cell Lymphoblastic Lymphoma (clinicaltrials.gov) - P3; N=1900; Active, not recruiting; Sponsor: National Cancer Institute (NCI); Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Acute Lymphoblastic Leukemia • CD2 • CD20 • CD22 • CD34 • CD5 • CD7 • CD8 • MPO