Asparlas (calaspargase pegol-mknl) / Servier, Takeda, Leadiant Biosci - LARVOL DELTA

Trial Treating Relapsed Acute Lymphoblastic Leukemia With Venetoclax and Navitoclax (clinicaltrials.gov) - P1/2 | N=35 | Active, not recruiting | Sponsor: St. Jude Children's Research Hospital | Trial completion date: Mar 2025 ➔ Feb 2027

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

Testing the Addition of the Anti-cancer Drug Venetoclax and/or the Anti-cancer Immunotherapy Blinatumomab to the Usual Chemotherapy Treatment for Infants With Newly Diagnosed KMT2A-rearranged or KMT2A-non-rearranged Leukemia (clinicaltrials.gov) - P2 | N=153 | Recruiting | Sponsor: National Cancer Institute (NCI) | Not yet recruiting ➔ Recruiting

Enrollment open • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology

OPTIMIZING ASPARAGINASE HYPERSENSITIVITY MANAGEMENT: REAL-WORLD EVIDENCE ON ASPARAGINASE SWITCHING PRACTICES AND GUIDELINE ADHERENCE (EHA 2025) - "Background: Calaspargase pegol (CAL-PEG) is a critical component of frontline treatment for acute lymphoblastic leukemia (ALL), contributing significantly to excellent outcomes... About 38% of patients who switched to recombinant Erwinia did so despite having ≤ grade 2 HSRs, with most occurring in induction. True antibody-mediated HSRs are rare after initial asparaginase exposure and some of these may represent infusion reactions. TDM can help distinguish true HSRs from infusion reactions, but its underuse suggests an opportunity to improve real-world management and reduce unnecessary asparaginase formulation switches."

Adherence • Clinical • HEOR • Real-world • Real-world evidence • Acute Lymphocytic Leukemia • Hematological Malignancies • Immunology • Leukemia • Oncology • Pediatrics

Disseminated Candidiasis in B-ALL: A Case Series, Diagnostic and Prophylactic Challenges (ASPHO 2025) - " Case 1: Seven year old girl with High Risk B-ALL undergoing treatment for relapse under AALL 1331 with mitoxantrone, vincristine, calaspargase pegol, and decadron. Primary workup for febrile neutropenia in the setting of new onset typhlitis confirmed by abdominal CT with initiation of meropenem...Bridged with blinatumomab with plan for future HSCT. Case 2: Three year old girl with High Risk B-ALL undergoing induction per AALL 1732 with IT cytarabine, vincristine, dexamethasone, daunorubicin, calaspargase and IT MTX...Treated successfully with micafungin and decadron. Case 3: Thirteen year old girl with High Risk B-ALL undergoing consolidation per AALL 1732 with cyclophosphamide, cytarabine, mercaptopurine, IT MTX, vincristine, and calaspargase... Underrepresentation of disseminated candidal disease may be present in centers not routinely utilizing mNGS to identify potential disease. Underlying prophylaxis regimens should be tailored to individual institutions and..."

Clinical • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Candidiasis • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Hepatology • Infectious Disease • Leukemia • Neutropenia • Oncology • Pain • Pneumonia • Respiratory Diseases

Correlating Calaspargase Pegol Therapeutic Drug Monitoring Data With Toxicity (ASPHO 2025) - "In the future, we hope to use the accumulated TDM data to individualize optimal dosing of calaspargase for our patients. We need to establish safe dose reduction criteria for those with high levels of calaspargase, in order to decrease delays in therapy and maintain efficacy."

Acute Lymphocytic Leukemia • Cardiovascular • Hematological Disorders • Hematological Malignancies • Hepatology • Immunology • Leukemia • Liver Failure • Lymphoma • Oncology • Pancreatitis • Pediatrics • Thrombosis

Identifying Rates and Risk Factors for Calaspargase Pegol-MKNL Toxicity in Patients With B-Cell All (ASPHO 2025) - "Our data shows no significant difference in the incidence of thrombosis or anaphylaxis among age, sex, and race/ethnicity. The incidence of hepatoxicity did differ significantly by age groups. Older patients (age 10+ years) had a higher incidence of hepatotoxicity than younger patients (9 years and younger) and are perhaps at greater risk of this adverse effect and subsequent complications."

Clinical • Acute Lymphocytic Leukemia • Cardiovascular • Hematological Disorders • Hematological Malignancies • Hepatology • Immunology • Leukemia • Oncology • Pancreatitis • Thrombosis

Economic Burden of Switching From Frontline to Second-Line Asparaginase in Pediatrics With ALL (ASPHO 2025) - "Background: Long-acting E.coli asparaginases (pegaspargase [PEG] and calaspargase pegol [CAL-PEG]) are critical components of frontline (1L) chemotherapy regimens in childhood acute lymphoblastic leukemia (ALL). Switching from 1L to 2L asparaginase is relatively common in pediatric ALL patients, which significantly increases treatment costs, mainly driven by higher outpatient medical costs of recombinant Erwinia. Consideration should be given to performing TDM, which may have important implications for mitigating unnecessary switches, as well as achieving substantial cost savings for payers."

Clinical • HEOR • Acute Lymphocytic Leukemia • Hematological Malignancies • Immunology • Leukemia • Oncology • Pediatrics

Managing Hypersensitivity Reactions After Asparaginase Treatment: A Systematic Literature Review (ASPHO 2025) - "As pediatric patients transitioned from pegaspargase (PEG) to calaspargase pegol (CAL-PEG) beginning December 2022, recent congress abstracts were searched post-SLR completion to capture data on CAL-PEG. HSRs are common with ASP, with varying prevalence across ASP formulations and protocols. This SLR demonstrated increasing use of premedication, despite insufficient evidence on its effectiveness. Large studies on desensitization are lacking, with small studies showing variable rates of success."

Review • Acute Lymphocytic Leukemia • Hematological Malignancies • Immunology • Leukemia • Oncology • Pediatrics

Evaluation of Calaspargase Pegol Reactions and Asparaginase Activity Level Monitoring (ASPHO 2025) - "Patients with severe reactions to calaspargase are transitioned to asparaginase Erwinia chrysanthemi (ERW), which is associated with lower incidence of reactions. Implementation of routine premedications and intravenous hydration for pediatric patients receiving calaspargase led to a decreased incidence of hypersensitivity reactions."

Acute Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Oncology • Pediatrics

The ALL-IN Approach: Confronting ALL With a Multi-Agent Chemotherapy Regimen (ASPHO 2025) - "Discuss the clinical safety profile, adverse reaction management, and important safety information for Asparlas. This non-CME symposium is supported by Servier Pharmaceuticals."

Acute Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Pediatrics

Total Therapy XVII for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia and Lymphoma (clinicaltrials.gov) - P2/3 | N=790 | Active, not recruiting | Sponsor: St. Jude Children's Research Hospital | Trial completion date: Mar 2028 ➔ Sep 2028

Trial completion date • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • BCL2

A Phase 2 Study to Evaluate Efficacy of Calaspargase Pegol-mknl and Decitabine Combined With Venetoclax in Pediatric, Adolescent, and Young Adult Patients With Relapsed/Refractory T-cell Acute Lymphoblastic Leukemia (T-ALL) and T- Cell Lymphoblastic Lymphoma (T-LLy) (clinicaltrials.gov) - P2 | N=22 | Not yet recruiting | Sponsor: M.D. Anderson Cancer Center | Initiation date: Feb 2025 ➔ Jun 2025

Trial initiation date • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • Pediatrics • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma

Higher Rates of Hypersensitivity Reactions to Calaspargase Compared With Pegaspargase: A Single Center Retrospective Review. (PubMed, Pediatr Blood Cancer) - "The current administration of Cal-PEG in large cooperative group trials will allow for a postmarketing exploration of the true risk of HSR and associated patient-specific risk factors."

Journal • Retrospective data • Acute Lymphocytic Leukemia • Hematological Malignancies • Immunology • Leukemia • Lymphoma • Oncology • Pediatrics

SPARK-ALL: Calaspargase Pegol in Adults with ALL (clinicaltrials.gov) - P2/3 | N=122 | Active, not recruiting | Sponsor: Institut de Recherches Internationales Servier | Trial completion date: Feb 2027 ➔ Feb 2026 | Trial primary completion date: Feb 2027 ➔ Feb 2026 | Recruiting ➔ Active, not recruiting

Enrollment closed • Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

Venetoclax Basket Trial for High Risk Hematologic Malignancies (clinicaltrials.gov) - P1 | N=92 | Recruiting | Sponsor: Andrew E. Place, MD | Trial completion date: Apr 2027 ➔ Jul 2028 | Trial primary completion date: Apr 2025 ➔ Jul 2026

Pan tumor • Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Myelodysplastic Syndrome • Oncology • ABL1 • BCL2 • BCR • FLT3 • IKZF1 • KMT2A

A 12-Step Desensitization Protocol for Calaspargase Pegol-mknl. (PubMed, J Pediatr Pharmacol Ther) - "Asparaginase Erwinia chrysanthemi (recombinant)-rywn (recombinant Erwinia) is an alternative for those with HSRs to pegaspargase. Here, we describe an 11-year-old boy with relapsed ALL who developed HSRs to both pegaspargase and recombinant Erwinia. This is the report of a novel desensitization protocol for calaspargase pegol-mknl (calaspargase) with no adverse events and adequate serum asparaginase activity."

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

Testing the Addition of the Anti-cancer Drug Venetoclax and/or the Anti-cancer Immunotherapy Blinatumomab to the Usual Chemotherapy Treatment for Infants With Newly Diagnosed KMT2A-rearranged or KMT2A-non-rearranged Leukemia (clinicaltrials.gov) - P2 | N=171 | Not yet recruiting | Sponsor: National Cancer Institute (NCI) | Initiation date: Jan 2025 ➔ Apr 2025

Trial initiation date • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • BCL2L1 • KMT2A • MCL1

Desensitization to calaspargase pegol appears to be less successful than pegaspargase. (PubMed, Blood Adv) - No abstract available

Journal

Adding Dasatinib Or Venetoclax To Improve Responses In Children With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia (ALL) Or Lymphoma (T-LLY) Or Mixed Phenotype Acute Leukemia (MPAL) (clinicaltrials.gov) - P2 | N=100 | Recruiting | Sponsor: St. Jude Children's Research Hospital | N=145 ➔ 100

Enrollment change • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Acute Lymphoblastic Leukemia • T Cell Non-Hodgkin Lymphoma • T-cell Acute Lymphoblastic Lymphoma

Studying the Effect of Levocarnitine in Protecting the Liver From Chemotherapy for Leukemia or Lymphoma (clinicaltrials.gov) - P3 | N=440 | Recruiting | Sponsor: Children's Oncology Group | Active, not recruiting ➔ Recruiting

Enrollment open • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Hepatology • Leukemia • Lymphoma • Oncology • T Acute Lymphoblastic Leukemia • CRLF2 • PNPLA3 • SOD2

Adding Dasatinib Or Venetoclax To Improve Responses In Children With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia (ALL) Or Lymphoma (T-LLY) Or Mixed Phenotype Acute Leukemia (MPAL) (clinicaltrials.gov) - P2 | N=145 | Recruiting | Sponsor: St. Jude Children's Research Hospital | Not yet recruiting ➔ Recruiting

Enrollment open • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Acute Lymphoblastic Leukemia • T Cell Non-Hodgkin Lymphoma • T-cell Acute Lymphoblastic Lymphoma

Studying the Effect of Levocarnitine in Protecting the Liver From Chemotherapy for Leukemia or Lymphoma (clinicaltrials.gov) - P3 | N=440 | Active, not recruiting | Sponsor: Children's Oncology Group | Trial completion date: Dec 2027 ➔ Dec 2028 | Trial primary completion date: Dec 2027 ➔ Jun 2028

Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Hepatology • Leukemia • Lymphoma • Oncology • T Acute Lymphoblastic Leukemia • CRLF2 • PNPLA3 • SOD2

Therapy for Newly Diagnosed Patients With B-Cell Precursor Acute Lymphoblastic Leukemia and Lymphoma (clinicaltrials.gov) - P2 | N=128 | Recruiting | Sponsor: St. Jude Children's Research Hospital | Not yet recruiting ➔ Recruiting

Enrollment open • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology

Calaspargase-Pegol-Mknl Combined with BCL-2 and MCL-1 Inhibition for Acute Myeloid Leukemia. (PubMed, Int J Mol Sci) - "Our previous studies have demonstrated that pegcrisantaspase (PegC), a long-acting Erwinia asparaginase, synergizes with the BCL-2 inhibitor Venetoclax (Ven) in vitro and in vivo; however, the anti-leukemic activity of E. coli-derived asparaginases in combination with BCL-2 inhibition, and potential synergy with inhibitors of MCL-1, a key resistance factor of BCL-2 inhibition, has yet to be determined. Using a combination of human AML cells lines, primary samples, and in vivo xenograft mouse models, we established the anti-leukemic activity of the BCL-2 inhibitor S55746 and the MCL-1 inhibitor S63845, alone and in combination with the long-acting E. coli asparaginase calaspargase pegol-mknl (CalPegA)...The S55746-CalPegA combination inhibited protein synthesis and increased eIF4E/4EBP1 interaction, suggesting an inhibition of translational complex formation. These results support the clinical evaluation of CalPegA in combination with BCL-2 inhibition for AML."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • BCL2 • EIF4E • EIF4EBP1

Anaphylaxis Associated with Calaspargase in Pediatric Patients with Acute Lymphoblastic Leukemia (ASH 2024) - "There have been different types of asparaginase products used in clinical trials over the years including Native or L-asparaginase, Erwinia asparaginase, Pegaspargase (PEG) and Calaspargase pegol-mknl (Cal-PEG)...Patients receiving Cal-PEG were more likely to have a diagnosis of anaphylaxis (2.9 vs 0.7%; OR 4.59, p<0.001), receive Epinephrine (35.5 vs 17.7%; OR 2.55, p <0.001) and had more admissions to the ICU (2.9 vs 1.7%; OR 1.75, p=0.101)...Venous thrombosis and hemorrhage were less associated with Cal-PEG, even though other toxicities remained the same between the two types of asparaginase. Anaphylaxis rates need to be prospectively confirmed in Children's Oncology Group studies, so that preventive strategy guidelines can be developed for these patients."

Clinical • Acute Lymphocytic Leukemia • Cardiovascular • Hematological Disorders • Hematological Malignancies • Hepatology • Immunology • Leukemia • Oncology • Pancreatitis • Pediatrics • Pulmonary Embolism • Respiratory Diseases