nelarabine / Generic mfg. - LARVOL DELTA

Nelarabine (NEL), Pegylated Asparginase (PEG) and Venetoclax (VEN) Incorporated to HCVAD Chemotherapy in the Frontline Treatment of Adult Patients with T-Cell Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma (T-ALL/T-LBL) (ASH 2023) - "Pts received 8 cycles (C) of HCVAD (C 1,3, 5, 7) alternating with high dose Ara-C and methotrexate (MTX) (C 2, 4, 6, 8) at approximately 3-week intervals...After the completion of the intensive phase; pts in all cohorts received 30 cycles of maintenance therapy with monthly POMP (prednisone, vincristine, MTX, prednisone) and early intensification with NEL/PEG on C6 and 7 and late intensification with MTX/PEG in C18 and HCVAD on C19... The ongoing phase 2 trial of NEL, ASP, VEN added to the HCVAD regimen shows promising long-term survival in adult pts with T-ALL/LBL with 3-yr OS of 76%-88% in pts treated with HCVAD+NEL+PEG +/- VEN. Larger prospective trials and longer follow-up are needed to demonstrate further benefit."

Clinical • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • Pediatrics • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma

Oncogenetic-Driven Targeted Therapy for Relapsed/Refractory T-Cell Acute Lymphoblastic Leukemia : A French ALL-Target Observatory Report (ASH 2023) - P | "In relapse/refractory (R/R) patients, standard of care treatments, including nelarabine, yield response rate of about 20-40% and responses are of short duration...For example, TTOs included Tofacitinib and Venetoclax (Tofa/Ven) in case of IL7R (CD127) expression or IL7R-pathway alterations (IL7RALT), 5-azacytidine and Venetoclax (Aza/Ven) in case of T-ALL/LL with epigenetic regulators alterations (DNMT3A, ASXL1, PHF6, TET2, PRC2, IDH1/2, SRSF2...) or Temsirolimus, Erwinase and Venetoclax (Tem/Erw/Ven) in case of PI3K signaling pathway alterations (PI3KALT)...Twenty-five patients received a TTO, including 14 Aza/Ven (56%), 8 Tofa/Ven (32%), 2 Tem/Erw/Ven (8%) and 1 Trametinib/Ven (4%)...A better knowledge of the oncogenetic landscape of T-ALL, and a close collaboration between clinicians and biologists, resulted in individualized treatment strategies. With a 3 months cumulative incidence of response of 70%, TTOs appear to be a promising approach in R/R T-ALL."

IO biomarker • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • ASXL1 • ATM • BCL2 • DNMT3A • IDH1 • IDH2 • IL7R • PHF6 • SRSF2 • TET2 • TP53

Mini-hyper-CVD with venetoclax (Ven) for patients with relapsed/refractory (R/R) Philadelphia chromosome (Ph)-negative acute lymphoblastic leukemia (ALL): A phase II study. (ASCO 2023) - P1/2 | " Pts ≥18 years with R/R Ph-negative B- or T-cell ALL received mini-HCVD alternating with methotrexate and cytarabine for up to 8 cycles...Rituximab (if CD20+ B-ALL) and prophylactic IT chemotherapy x8 doses were given for the first 4 cycles. Pts with T-ALL received additional 2 cycles of nelarabine and peg-asparaginase during consolidation without Ven, and 2 cycles during maintenance. Maintenance with vincristine, prednisone and Ven was given for up to 2 years...Among the 18 B-ALL pts, 16 (89%) had received prior blinatumomab and 7 (39%) prior inotuzumab... The combination of low-intensity chemotherapy mini-HCVD with Ven in pts with R/R Ph-negative ALL was well-tolerated and resulted in a response rate of 67%. Further studies examining the role of Ven-based therapies in ALL are needed for newly diagnosed and R/R pts. Clinical trial information: NCT03808610."

Clinical • P2 data • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • Transplantation • CD20

DONOR SELECTION STRATEGY IS CRITICAL IN DETERMINING OUTCOMES OF HIGH-RISK, PAEDIATRIC, RELAPSED, MRD POSITIVE T-ALL HSCT (EBMT 2026) - "All except one received TBI-based myeloablative conditioning: approximately half received etoposide with 12 Gy TBI, and the remainder cyclophosphamide with 14.4 Gy TBI...Cord blood transplants were T-cell-replete (TRCBT) with ciclosporin ± mycophenolate mofetil as GVHD prophylaxis. Matched sibling donor (MSD) transplants used methotrexate plus ciclosporin as GVHD prophylaxis.Of 39 patients, 11 received MSD bone-marrow grafts... Relapse remains the leading cause of HSCT failure in T-ALL, particularly in CR2 patients with persistent pre-transplant MRD. Where disease is chemo responsive, deeper pre-transplant cytoreduction—such as with nelarabine—may be beneficial. Our data suggest that in cases of refractory MRD, prioritising non-serotherapy platforms like MSD HSCT or TRCBT may better harness GVL and improve RFS and OS."

Minimal residual disease • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Pediatrics • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma

Risk-Adjusted Therapies Yield Equivalent Outcomes for Adolescents and Young Adults (AYAs) Treated for Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia (T-ALL) on Children's Oncology Group (COG) Studies AALL0434 and AALL1231 (ASH 2023) - "On AALL0434, participants were randomized to receive escalating dose methotrexate (CMTX) without leucovorin rescue + pegaspargase or high dose MTX (HDMTX) + leucovorin rescue. Intermediate and high-risk patients were randomized to receive or not receive six 5-day courses of nelarabine (Nel)...Key differences between AALL0434 and AALL1231 ABFM backbones included the use of prednisone in induction in AALL0434 versus dexamethasone in AALL1231, and cranial radiation therapy in the majority of AALL0434 participants versus only in patients with central nervous system involvement in AALL1231...Despite small numbers, CMTX holds a survival advantage for AYA T-ALL patients, with no survival disadvantage seen among AYA T-ALL patients who received Nel. Bortezomib does not offer significant benefit for AYA T-ALL patients."

Clinical • Acute Lymphocytic Leukemia • CNS Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Oncology • Respiratory Diseases • Septic Shock • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma

Shorla Oncology…announced that the U.S. Food and Drug Administration has approved the company’s oncology drug, Nelarabine Injection, in a larger vial size, 375mg/75mL, for adult and pediatric patients with T-cell Acute Lymphoblastic Leukemia (T-ALL) and T-cell Lymphoblastic Lymphoma (T-LBL) (Businesswire) - "This larger vial size is the second FDA approval of Nelarabine Injection from Shorla, both using the same formulation. The first approval, for a 250mg/50mL vial, was introduced to help address ongoing product shortages in the U.S. market. Depending on the dose, the new 375mg/75mL vial offers greater dosing flexibility for pediatric patients and provides higher-dosing options for adults."

FDA approval • T Acute Lymphoblastic Leukemia • T Lymphoblastic Lymphoma

Venetoclax Added to Hyper-CVADNelarabine and Pegylated Asparagine Improves Outcomes in Patients With T-Cell Acute Lymphoblastic Leukemia/ Lymphoma (SOHO 2024) - P2 | " The ongoing phase 2 clinical trial of hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, adriamycin, and dexamethasone alternating with methotrexate and cytarabine) with nelarabine and pegylated asparaginase (PegAsP) (NCT00501826) has shown promising response rates and survival in adult patients with T-ALL/LBL in the frontline settings (original cohort). Addition of venetoclax to hyper-CVAD-nelarabine-PegAsp is promising and tolerable in the frontline setting for adult patients with T-ALL/LBL."

Clinical • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • T Acute Lymphoblastic Leukemia

Longitudinal follow up of a phase 2 trial of venetoclax added to hyper-CVAD, nelarabine and pegylated asparaginase in patients with T-cell acute lymphoblastic leukemia and lymphoma. (PubMed, Leukemia) - "Febrile neutropenia was the most common serious adverse event, seen in 60% patients. The addition of venetoclax to HyperCVAD-nelarabine-pegylated asparaginase was tolerable and led to improvement in DOR and PFS."

Journal • P2 data • Acute Lymphocytic Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Neutropenia • Oncology • T Acute Lymphoblastic Leukemia

A phase 1 study to evaluate the safety, pharmacology, and feasibility of continuous infusion nelarabine in patients with relapsed and/or refractory lymphoid malignancies. (PubMed, Cancer) - "Preliminary evaluation of continuous infusion schedule of nelarabine suggests that the safety profile is acceptable for this patient population, with clinical activity observed even at low doses and could broaden the use of nelarabine both as single agent and in combinations by potentially mitigating the risk of central nervous system toxicities."

Journal • P1 data • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • Pain • Prolymphocytic Leukemia • T Acute Lymphoblastic Leukemia

Frontline Consolidation with Nelarabine for Adults with High-Risk T-Cell Acute Lymphoblastic Leukemia. Results of the Graall-2014/T Atriall Phase 2 Study (ASH 2023) - "NELA was given at 1,500 mg/sqm/day at day 1,3 and 5 in combination with etoposide and cyclophosphamide for a maximum of 5 courses during consolidation (2 cycles) and maintenance (3 cycles). While NELA did not yield an overall improved outcome in the study population, benefits were observed in favorable MRD responders and non-ETP patients. Additional prospective studies are needed to further delineate the specific patient subgroups that might benefit from NELA."

Clinical • P2 data • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • Transplantation • FBXW7 • NOTCH1 • PTEN

ADVANCING CHEMOGENOMIC STRATEGIES FOR FUNCTIONAL PRECISION MEDICINE IN RELAPSED/REFRACTORY T-ALL AND ETP-ALL: PRELIMINARY RESULTS OF THE GIMEMA ALL2720 TRIAL (EHA 2025) - P=N/A | "In response to this unmet clinical need, we developed a chemogenomic platform aimed at identifying potential therapeutic alternatives to nelarabine, the only single agent currently approved for patients with relapsed or refractory (R/R) T-ALL... In conclusion, we suggest that a coordinated, unified platform can address the needs of large, densely populated countries by delivering functional genomic data to guide "on-time" therapeutic decisions. Our results indicate that nearly 40% of R/R T-ALL cases, especially ETP with unknown subtype-defining oncogenic lesions, can be rescued through a tandem DRP-alloHSCT, providing a long-term solution for this aggressive disease."

IO biomarker • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • BCL2 • CDKN2B • NOTCH1 • TLX1

AALL2331: Testing the Addition of Daratumumab to Chemotherapy for Treating Patients With Newly-Diagnosed T-Cell Lymphoblastic Leukemia (T-ALL) and T-Cell Lymphoblastic Lymphoma (T-LL) (clinicaltrials.gov) - P2/3 | N=1708 | Not yet recruiting | Sponsor: Children's Oncology Group | Initiation date: Mar 2026 ➔ Jun 2026

Trial initiation date • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Acute Lymphoblastic Leukemia

The Subject Expert Committee (SEC) of the Central Drugs Standard Control Organisation (CDSCO) has recommended grant of permission to Zydus Lifesciences Limited to conduct a Phase IV clinical trial of Nelarabine Injection 250 mg/50 ml, as per the revised protocol submitted by the firm. (Medical Dialogues) - "The decision was taken under file number ND/CT/25/000013, with the committee directing that the trial results be submitted to CDSCO for further review."

New P4 trial • T Acute Lymphoblastic Leukemia • T Lymphoblastic Lymphoma

CDSCO Panel Seeks Revised Phase IV Trial Protocol for MSN Lab's Nelarabine Injection (Medical Dialogues) - "Highlighting the need for stronger post-marketing safety oversight, the Subject Expert Committee (SEC) of the Central Drugs Standard Control Organisation (CDSCO), has directed MSN Laboratories Private Limited to revise and resubmit the Phase IV clinical trial protocol for Nelarabine Injection 250 mg/50 ml (5 mg/ml) within one month, before the study can proceed. The committee reviewed the proposal in line with the conditions stipulated at the time of granting permission for the manufacture and marketing of Nelarabine Injection. As part of its post-marketing commitment, the firm presented a Phase IV clinical trial titled 'A Phase IV, Open-label, Multicenter Study to Evaluate the Long-term Safety and Effectiveness of Nelarabine Injection 250 mg/50 mL (5 mg/mL) in Adult Patients with Relapsed or Refractory T-Acute Lymphoblastic Leukaemia (T-ALL) / Lymphoblastic Lymphoma (T-LBL)'."

Clinical protocol • T Acute Lymphoblastic Leukemia • T Lymphoblastic Lymphoma

CAVALRY: Trial to Test Safety of Adding Capivasertib to a Standard Leukemia Treatment Regimen (clinicaltrials.gov) - P1/2 | N=104 | Not yet recruiting | Sponsor: University of Chicago

New P1/2 trial • Hematological Malignancies • Leukemia • Lymphoma • Oncology

Optimization of upfront therapy for adult acute lymphoblastic leukemia: a paradigm shift toward immunotherapy. (PubMed, Med Oncol) - "Targeted immune therapies like blinatumomab, inotuzumab ozogamicin (InO), rituximab, and nelarabine are being combined with traditional chemotherapy protocols to enhance remission rates and minimal residual disease (MRD) negativity while decreasing toxicities...Ph + ALL patients receive standard treatment with multi-agent chemotherapy and TKIs dasatinib or ponatinib and blinatumomab as part of their frontline therapy to enhance molecular responses and minimize the requirement for allogeneic hematopoietic stem cell transplantation (allo-HCT)...The practice of testing MRD and genomic profiling at diagnosis revolutionized treatment approaches by allowing personalized curative strategies for all patients. Research on clinical trials aims to establish the best sequence of targeted therapies and CAR T-cell therapy for high-risk and MRD-positive patients to achieve longer survival rates with reduced toxicity and less dependence on allo-HCT in first remission."

Journal • Review • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Pediatrics • T Acute Lymphoblastic Leukemia • Transplantation • CD20

E2F transcription factors as multimodal biomarkers for pan-cancer management. (PubMed, Sci Rep) - "There existed a positive correlation between E2F2 expression level and Dasatinib sensitivity, negatively related to drug sensitivity of Nelarabine, XK-469, Cyclophosphamide, etc. Pazopanib, Doxorubicin, and Paclitaxel sensitivity was all positively associated with E2F5 expression. According to these analysis and validation results, E2F genes are relevant to the occurrence and progression of various cancers, which may be biomarkers for tumor diagnostics and prognosis. The discovery of new therapeutic targets can lead to reshaping TME to promote tumor-suppressive metastasis rather than tumor-friendly metastasis."

Biomarker • IO biomarker • Journal • Pan tumor • Tumor mutational burden • Bladder Cancer • Genito-urinary Cancer • Microsatellite Instability • Oncology • Solid Tumor • E2F2 • E2F5 • E2F7 • MSI • TMB

Molecular subtypes and BH3 mimetic synergy with anti-leukemia agents in T-cell acute lymphoblastic leukemia (ASH 2025) - "In this study, we evaluated the ex vivo cytotoxicity of threeinvestigational BH3 mimetics, namely AZD4320 (BCL2/BCL-XL dual inhibitor), AZ'3202 (BCL-XL inhibitor),and AZD5991 (MCL1 inhibitor), using an imaging-based cell viability assay in a panel of 58 patient-derivedxenograft (PDX) models of T-ALL...These findings highlightthe interplay between molecular subtype and apoptotic signaling and their effects on BH3 mimeticsensitivity in T-ALL.Next, to investigate the therapeutic potential of BH3 mimetics in combination settings for T-ALL, weevaluated the interactions between AZD4320 and key anti-leukemic agents, i.e., asparaginase,prednisolone, nelarabine, and an LCK inhibitor, dasatinib, across 40 T-ALL PDX samples ex vivo...In three T-ALL PDX models, the combination of AZD0466 (a drug-dendrimer conjugateof AZD4320) with asparaginase consistently exhibited greater efficacy compared to monotherapy (vsAZD0466, P = 0.0007, P = 0.015, and P = 0.0006; vs asparaginase, P =..."

Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • BCL2 • BCL2L1

Mixed-Phenotype Acute Leukemia Transforming Into Acute Myelomonocytic Leukemia (AML M4): A Case Report and Therapeutic Challenges. (PubMed, Cureus) - "Hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD) induction achieved morphological complete remission, but measurable residual disease (MRD) persisted. Consolidation with mini-cyclophosphamide, vincristine, and dexamethasone (mini-CVD) and prednisone, vincristine, methotrexate, and 6-mercaptopurine (POMP) maintenance failed to eradicate MRD, and overt relapse occurred at month 7. Nelarabine salvage was initiated...Early molecular risk stratification and deployment of targeted agents, venetoclax-based combinations, or timely allogeneic transplantation should be considered before irreversible genomic complexity emerges. Prospective studies tailored to high-risk cytogenetic subsets of MPAL are urgently needed."

Journal • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Novel Coronavirus Disease • Oncology • Pulmonary Disease • Respiratory Diseases • Transplantation • IDH2

Determination of Nelarabine Stability When Packaged in Polypropylene Syringes (ASHP 2025) - No abstract available

Utilization patterns of venetoclax-based regimens for AML in a community based setting & representative populational analyses (ASH 2025) - "In first line setting, 22 patients (52.3%) received Venetoclax with azacitidine, 17 patients 40.1% received decitabine, 2 patients (4.8%) with cladribine and cytarabine, and 2 patients (4.8%) received Venetoclax alone...6 patients (40%) received azacitidine with venetcloax, 6 patients (40%) received decitabine, 1 patient (6.7%) received cytarabine, 1 patient (6.7%) received enasidenib, and one patient (6.7%) received nelarabine, cyclophosphamide, and cytarabine... The median age at diagnosis was 64 years (range 21-86). 47% patients were female gender. 24.5% of patients were Black or African-American, 71.4% were White, 1% were Asian, and 3.1% were more than one race."

Clinical • Acute Myelogenous Leukemia • Febrile Neutropenia • Hepatology • Liver Failure • Neutropenia • Renal Disease • CEBPA • DDX41 • NPM1 • TP53

Predictors of outcome in adult patients with Relapsed/Refractory T-cell acute lymphoblastic leukemia (ASH 2025) - "Common mutations included NOTCH1 (50%), TET2(45.7%), ASXL1 (34.3%), and RAS pathway mutations (24.4%); Complex cytogenetics and KMT2Arearrangements were seen in in 10% and 4%, respectively.Frontline (F/L) regimens included HCVAD (46%), nelarabine-based (34%), pediatric-inspired regimens (9%),and venetoclax (VEN)-based regimens (6%). R/R T-ALL carried poor prognosis, with a median OS of 8.1 months and 2-year OS of only14%. Achieving CR in S1, undergoing SCT, and use of nelarabine were independently associated withimproved survival. In the ETP-ALL subset, nelarabine use and achieving CR remained significant inmultivariate analysis."

Biomarker • Clinical • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • ASXL1 • KMT2A • NOTCH1 • TET2

Longitudinal clonotype tracking by next-generation sequencing (NGS) based T-cell receptor (TCR) rearrangement measurable residual disease (MRD) assay in frontline adult T-acute lymphoblastic leukemia (ALL) (ASH 2025) - "Most common treatment was combination of hyper-CVAD with nelarabine,pegasparaginase and/or venetoclax (n=33, 87%). After adjusting for non-leukemic tracking sequences, pts with the persistent NGS MRD during theintensive phase of therapy had significantly higher risk of relapse than those who achieved NGS MRDnegativity. Our findings suggest that NGS MRD is prognostic in T-ALL, although more pts with longerfollow-up are needed to determine the prognostic impact of NGS MRD dynamics and outcomes in T-ALL."

Clinical • IO biomarker • Next-generation sequencing • Residual disease • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • T Acute Lymphoblastic Leukemia • TRB • TRG

Cell-free application of Deltex1 to suppress hyperactive notch signaling in t-cell acute lymphoblastic leukemia (ASH 2025) - "Transcriptomic analysis revealed a significant decrease in Notch pathway activity andin cell cycle progression of T-ALL that receive nanoparticle treatment. Furthermore, the nanoparticletreatment synergized with existing standard-of-care chemotherapy such as Nelarabine, indicating a novelclinically relevant approach for treating refractory T-ALL."

Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • T Acute Lymphoblastic Leukemia • Targeted Protein Degradation • T-cell Acute Lymphoblastic Lymphoma • NOTCH1

Nelarabine treatment before allogeneic stem cell transplantation was associated with an increased risk of neurological adverse events in patients with T-ALL/lbl: A retrospective study of the kanto study group for cell therapy. (ASH 2025) - "In multivariate analysis, NEL treatment was identified asan independent risk factor for NRM (HR = 5.7; p 50 years) (HR= 3.2; p = 0.023), but not for OS (HR = 2.9; p = 0.055).[Conclusion] These findings suggest that NEL treatment before SCT might be associated with a higher riskof clinically relevant NAEs in T-ALL/LBL patients. Further investigation is warranted to elucidate the riskfactors for NAEs following SCT in patients treated with NEL, and to better define the impact of NEL ontransplant outcomes in a larger cohort."

Adverse events • Retrospective data • Acute Lymphocytic Leukemia • CNS Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Lymphoblastic Lymphoma • Lymphoma • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • Transplantation • Vascular Neurology