nelarabine / Generic mfg. - LARVOL DELTA

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

DONOR LYMPHOCYTE INFUSIONS FOR ACUTE LYMPHOBLASTIC LEUKEMIA: A RETROSPECTIVE SINGLE-CENTER ANALYSIS (EBMT 2025) - "They received a median of 4 DLIs (1-12); DLIs were given in association with TKI in Ph+ ALL, with blinatumomab in 1 Ph-ALL , with nelarabine in one T-ALL and off-label bortezomib in another...They received a median of 3 DLIs (2-4), with TKI in Ph+ B-ALL, inotuzumab in Ph- ALL and radiotherapy in T-ALL... Nearly 40% of ALL patients needed DLI, primarily for MRD positivity. DLI can be curative and safe, particularly in the prophylactic/pre-emptive setting and in combination with other therapies. Prospective trials are needed to assess their role in the era of MRD monitoring and novel agents."

Retrospective data • Acute Graft versus Host Disease • Acute Lymphocytic Leukemia • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Oncology • T Acute Lymphoblastic Leukemia

DONOR LYMPHOCYTE INFUSIONS FOR ACUTE LYMPHOBLASTIC LEUKEMIA: A RETROSPECTIVE SINGLE-CENTER ANALYSIS (EBMT 2025) - "They received a median of 4 DLIs (1-12); DLIs were given in association with TKI in Ph+ ALL, with blinatumomab in 1 Ph-ALL , with nelarabine in one T-ALL and off-label bortezomib in another...They received a median of 3 DLIs (2-4), with TKI in Ph+ B-ALL, inotuzumab in Ph- ALL and radiotherapy in T-ALL... Nearly 40% of ALL patients needed DLI, primarily for MRD positivity. DLI can be curative and safe, particularly in the prophylactic/pre-emptive setting and in combination with other therapies. Prospective trials are needed to assess their role in the era of MRD monitoring and novel agents."

Retrospective data • Acute Graft versus Host Disease • Acute Lymphocytic Leukemia • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Oncology • T Acute Lymphoblastic Leukemia

UKALL14: Standard Chemotherapy with or Without Nelarabine or Rituximab in Treating Patients with Newly Diagnosed Acute Lymphoblastic Leukemia (clinicaltrials.gov) - P=N/A | N=0 | Completed | Sponsor: University College, London | Active, not recruiting ➔ Completed | N=1033 ➔ 0 | Trial completion date: Dec 2025 ➔ Feb 2025

Enrollment change • Trial completion • Trial completion date • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Mucositis • Oncology • Stomatitis • ABL1 • BCR • MYC

The niosomal nelarabine as a promising nano combination for retinoblastoma treatment: an in vitro study-experimental research. (PubMed, Ann Med Surg (Lond)) - "After cultivation of the Y79 cell line, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test was performed to determine IC50 of niosomal nelarabine (Nio-Nelarobine) and also the cytotoxicity of Nio-Nelarobine and doxorubicin against Y79 cell line was investigated. Nio-Nelarobine may be a functional therapeutic combination for RB treatment. Further experimental and preclinical investigations are necessary to verify this impact in greater detail."

Journal • Preclinical • Eye Cancer • Oncology • Retinal Disorders • Retinoblastoma • Solid Tumor • AKT1 • FOXO1 • PTEN

Nelarabine in T-cell acute lymphoblastic leukemia: intracellular metabolism and molecular mode-of-action. (PubMed, Leukemia) - "A critical avenue of research in need of development is investigation of nelarabine combination therapies, both in the context of current T-ALL chemotherapy regimens and with emerging anti-leukemic agents, and we highlight some areas to pursue. Altogether, we discuss what we can learn from the preclinical literature as a whole and present our view for future research regarding nelarabine treatment in T-ALL."

Journal • Review • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma

Therapeutic drug monitoring in acute lymphoblastic leukemia-a deep dive into pharmacokinetics, -dynamics, and -genetics of antileukemic drugs. (PubMed, Expert Rev Clin Pharmacol) - "This narrative review covers the pharmacokinetics (PK), -dynamics (PD) and-genetics of classic chemotherapeutic drugs used in frontline therapy for acute lymphoblastic leukemia (ALL), including anthracyclines, asparaginase, busulfan, cyclophosphamide, cytarabine, glucocorticoids, methotrexate, nelarabine, thiopurines, tyrosine kinase inhibitors, and vincristine. Furthermore, novel immunotherapies including blinatumomab, inotuzumab ozogamicin, and chimeric antigen receptor T-cells that are rapidly moving into frontline therapy are addressed...Some of the drugs have been used in ALL treatment regimens for decades, but a wide range of new compounds are being introduced, some like blinatumomab reaching standard-of-care designation. Not least, optimized drug efficacy and reduction of the risk of serious toxicities may render TDM implementation cost-effective."

Journal • PK/PD data • Review • Acute Lymphocytic Leukemia • Genetic Disorders • Hematological Malignancies • Leukemia • Obesity • Oncology

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

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

The efficacy and safety of nelarabine in relapsed or refractory T-cell acute lymphoblastic leukemia: a systematic review and meta-analysis. (PubMed, Ann Hematol) - "However, its use, both as monotherapy and in combination therapy, is associated with considerable adverse events, particularly neurotoxicity and hematologic toxicities, necessitating careful monitoring. Further research is needed to optimize its application across diverse patient populations and to better manage its associated toxicities."

Journal • Retrospective data • Acute Lymphocytic Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Lymphoma • Neutropenia • Oncology • Pain • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • Thrombocytopenia

GMALL: Optimization of Therapy in Adult Patients with Newly Diagnosed Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma by Individualised, Targeted and Intensified Treatment (clinicaltrials.gov) - P3 | N=1000 | Completed | Sponsor: Goethe University | Active, not recruiting ➔ Completed | Trial completion date: Jul 2025 ➔ Dec 2024 | Trial primary completion date: Aug 2022 ➔ Dec 2024

Trial completion • Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • Alzheimer's Disease • Hematological Malignancies • Leukemia • Lymphoma • Oncology • T Acute Lymphoblastic Leukemia

DFCI 16-001: Treatment of Newly Diagnosed Acute Lymphoblastic Leukemia in Children and Adolescents (clinicaltrials.gov) - P3 | N=560 | Active, not recruiting | Sponsor: Dana-Farber Cancer Institute | Trial primary completion date: Nov 2024 ➔ Nov 2026

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

Mitochondria-associated programmed cell death: elucidating prognostic biomarkers, immune checkpoints, and therapeutic avenues in multiple myeloma. (PubMed, Front Immunol) - "57 drugs, including nelarabine and vorinostat, were predicted to interact with the prognostic genes. Seven genes (TRIAP1, TOMM7, PINK1, CHCHD10, PPIF, BCL2L1, NDUFA13) involved in mitochondrial function and PCD pathways were identified as prognostic markers in MM. These findings provide insights into MM biology and prognosis, highlighting potential therapeutic targets."

Biomarker • Journal • Hematological Disorders • Hematological Malignancies • Metabolic Disorders • Multiple Myeloma • Oncology • BCL2L1 • CHCHD1 • NDUFA13 • PPIF

A Phase I/II Study of Mini-Hyper-CVD, Venetoclax and Navitoclax in Patients with Relapsed/Refractory Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia (ASH 2024) - "Pts with CD20+ ALL also received up to 8 doses of rituximab...Among the 12 pts with B-cell ALL, all had received prior blinatumomab and 9 (75%) had received prior inotuzumab ozogamicin; among the 10 pts with T-cell ALL/LBL, 5 (50%) had received prior nelarabine...Notably, all 3 pts with R/R ETP ALL achieved CR. While response rate and survival appear better than historical expectations with chemotherapy alone in this population, these outcomes appear similar to those achieved with mini-hyper-CVD + venetoclax in a similar cohort of pts with R/R Ph- ALL (Short NJ et al Blood Adv 2023), questioning the benefit of adding a Bcl-xL inhibitor to this regimen."

Clinical • P1/2 data • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Lymphoma • Neutropenia • Oncology • BCL2 • BCL2L1 • CD20

Augmented Hyper-CVAD (AHCVAD), a Pediatric Inspired Regimen for Adults Younger Than 50 Years of Age with Acute Lymphoblastic Leukemia (ALL), Yields High Rates of MRD Negativity, Favorable 3-Year Overall Survival Regardless of Allogeneic Stem Cell Transplant (ASCT): A Single Center Experience (ASH 2024) - "Similar to pediatric regimens, AHCVAD uses intensified doses of vincristine, dexamethasone, and pegaspargase and shows activity in relapsed pts with ALL (Faderl S et al : Clin Lymphoma Myel Leuk 2011)...Pts with CD20+ ALL also received Rituximab at 375 mg/m2 on days 1 and15 of cycles 1 to 4. In pts with T-ALL, two cycles of Nelarabine were given following AHCVAD cycles 4 and 5, respectively, and repeated during maintenance cycles 12 and 24...Those who didn't achieve MRD negativity after 2 cycles were switched to blinatumomab or inotuzumab ozogamicin...The augmentation of the hyper-CVAD backbone in this fashion may be more feasible in the community setting than other pediatric protocols. However, intensive monitoring with appropriate antibiotic, antiviral prophylaxis and growth factor support is required given significant toxicities observed."

Clinical • Minimal residual disease • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Burkitt Lymphoma • Cardiovascular • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Lymphoma • Oncology • Pediatrics • T Acute Lymphoblastic Leukemia • Thrombosis • Transplantation • ABL1 • BCR • CD20

Survival and Therapeutic Outcomes in T-Cell Prolymphocytic Leukemia (T-PLL): A Collaborative Multi-Center Study Cohort (ASH 2024) - "Other active second-line treatments included : pentostatin (n=23; 44% ORR, 17% CR), ruxolitinib-based regimens (n=4; 25% ORR, 0% CR), venetoclax-based regimens (n=13; 39% ORR, 8% CR), bendamustine (n=10; 30% ORR, 0% CR), and nelarabine (n=4; 75% ORR, 50% CR)...Conclusions : In this large, multi-center study of T-PLL, frontline treatment with a combination of alemtuzumab/pentostatin improved response rates and OS...Intriguingly, TCL1A+, and CD4- T- PLL had worse OS/PFS, and scRNAseq confirmed unique molecular signatures in these populations, suggesting these represent novel molecular subtypes of T-PLL with prognostic significance. These studies form the foundation for future, targeted, therapeutic studies in this rare, aggressive disease with few treatment options."

Clinical • Hematological Malignancies • Leukemia • Oncology • Prolymphocytic Leukemia • CD4 • CD8 • TCL1A

Integrating Genomics and Functional Phenotypes to Refine Risk Assessment in Acute Myeloid Leukemia across the Age Spectrum: Insights from Singapore (ASH 2024) - "For DBP, nine pediatric AML tumors were treated with cytarabine, daunorubicin, etoposide, and fludarabine, while 12 T-ALL samples were treated with nelarabine, vincristine, dasatinib, asparaginase, and dexamethasone...Direct mitochondrial sensitivity to venetoclax in lymphoblasts was higher in T-ALL (n=29) than in B-ALL (n=47). Lymphoblasts showed greater direct mitochondrial sensitivity to navitoclax, suggesting the potential use of dual inhibition of BCL2 and BCL-XL in ALL...The consistent sensitivity of lymphoblasts and myeloblasts to BCL-2 inhibition across age groups and lineages suggests the broad applicability of our approach. By integrating cellular vulnerabilities to anti-apoptotic proteins into clinical assessments, we may significantly improve treatment decision-making and risk stratification in acute leukemia."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics • T Acute Lymphoblastic Leukemia • BCL2L1 • MCL1

Combination Therapy with Nelarabine, Peg-Asparaginase and Venetoclax for Adults Patients with Relapsed/Refractory T-Cell ALL (ASH 2024) - "The median OS of the whole cohort was 9.1 months and the median RFS of the responders was 23 months. NEL-PEG-VEN regimen is an effective therapy in getting this difficult to treat population into a remission, allowing them to proceed with a potentially curative allo-SCT."

Clinical • Combination therapy • Bone Marrow Transplantation • Oncology • T Acute Lymphoblastic Leukemia • FBXW7 • NOTCH1 • TP53

Utility of Obtaining Follow-Up Blood Cultures in Gram-Negative Bacterial Bloodstream Infection Among Patients With Hematologic Malignancies. (PubMed, Cureus) - "We found a few cases of positive FUBC. Routine FUBC may not be appropriate for all GNBSI patients with hematological malignancies, particularly during the current blood culture bottle shortage."

Gram negative • Journal • Acute Myelogenous Leukemia • Febrile Neutropenia • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Oncology • Pneumonia

Outcome of Patients with Hematologic or Molecular Relapsed/Refractory (R/R) Acute T- Lymphoblastic Leukemia - Data from the GMALL Study Group (ASH 2024) - "Nelarabine however appeared not be effective in molFail/molRel T-ALL. Our analysis provides reference for future trials with new compounds in hemR/R or molR/R T-ALL."

Clinical • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Pediatrics • T Acute Lymphoblastic Leukemia

Prognostic Factors for T-Cell Acute Lymphoblastic Leukemia in Children and Young Adults: ALL-T11 Study Conducted By Japan Children's Cancer Group and Japan Adult Leukemia Study Group (ASH 2024) - "Until the measurement of TP2 PCR-MRD, all patients were treated with an identical therapy that was intensified with dexamethasone instead of prednisolone in remission induction therapy IA and L-asparaginase in consolidation therapy IB. In the Cox proportional hazard model, we found that CNS-3c and TP2 PCR-MRD had significant impacts for poorer EFS (HR=3.37, 95% CI=1.30–8.70, p=0.012, HR=4.59, 95% CI=2.10–10.06, p<0.001) and OS (HR=5.48, 95% CI=1.83–16.41, p=0.002, HR=4.61, 95% CI=1.69–12.58, p=0.003) and only CNS-3c was significant for higher CIR (HR=3.97, 95% CI=1.30–12.08, p=0.015). Conclusion : This study found a prognostic impact of CNS-3c on EFS, OS, and CIR, even with the use of CRT and regimens with nelarabine, whereas patients with CNS-3a/3b had a comparable prognosis to those with CNS-1/2."

Biomarker • Clinical • Acute Lymphocytic Leukemia • CNS Disorders • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia

Outcome of an Urban Cohort of North American Adult T-Cell Leukemia/Lymphoma Patients (ASH 2024) - "Ten (45%) patients received CNS prophylaxis including intrathecal (IT)-MTX 50%, HD-MTX 30%, and IT-cytarabine 20%...Patients attaining CR or PR who were eligible for alloSCT based on donor availability and comorbidity score, received bridging therapy with several cycles of brentuximab (if CD30+) or nelarabine...Within the limitations of a single institution cohort, we report that age and WBC count at diagnosis are associated with a worse OS. Accurate diagnosis and early referral to centers with transplant and clinical trial availability is key to management of ATLL patients."

Clinical • Adult T-Cell Leukemia-Lymphoma • Bone Marrow Transplantation • Candidiasis • Hematological Malignancies • Hepatology • Human Immunodeficiency Virus • Infectious Disease • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Pulmonary Disease • Respiratory Diseases • TNFRSF8 • TP53

Donor Lymphocyte Infusions in Acute Lymphoblastic Leukemia: A Single-Center Retrospective Analysis (ASH 2024) - "All but 2 patients have received an in vivo T cell depletion either with ATG, or post-transplant cyclophosphamide (for MMUD and HAPLO)...They received a median of 4 DLIs (1-12); DLIs were given in association with TKI in Ph+ ALL patients, with blinatumomab in 1 Ph- ALL case, with nelarabine in 1 T-ALL patient and with off-label bortezomib in 1 T-ALL patient...They received a median of 3 DLIs (2-4), given with TKI in Ph+ B-ALL, inotuzumab in Ph- ALL and radiotherapy in T-ALL...DLI can be an active and safe treatment for ALL, especially if used in the prophylactic/pre-emptive setting and in combination with other therapies. Better evaluation of DLI efficacy in prospective clinical trials is needed in the era of MRD monitoring and novel agents."

Retrospective data • Acute Graft versus Host Disease • Acute Lymphocytic Leukemia • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Oncology • T Acute Lymphoblastic Leukemia

Nelarabine Is Active in Pediatric T/Myeloid Mixed Phenotype Acute Leukemia (ASH 2024) - "Furthermore, our in silico drug sensitivity analysis predicts malignant blasts are more sensitive to nelarabine in T/My MPAL compared to B/My MPAL. Larger studies should be performed to validate these findings, but our data support the use of nelarabine in pediatric patients with T/My MPAL."

Clinical • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Infectious Disease • Leukemia • Lymphoma • Oncology • Pediatrics • T Acute Lymphoblastic Leukemia

Revolutionizing B-ALL Cell Line Development: Novel Generation to Uncover Therapeutic Vulnerabilities (ASH 2024) - "LH lines showed resistance to many cytotoxic drugs, especially birinapant, inotuzumab, dexamethasone, and nelarabine...Additionally, we found LH samples also respond well to vincristine and JQ1, suggesting new vulnerabilities. Surprisingly, BCR : : ABL1+/BCR : : ABL1-like samples with IK6 were sensitive to dexamethasone and gilteritinib compared to those with wild type IKZF1, though complete cell eradication was not achieved even at high dosage, indicating combined therapy would be beneficial.In summary, we developed a new approach, generating 21 B-ALL cell lines spanning 11 subtypes. Combined with commercial lines, we now have seven LH lines, eight BCR : : ABL1-like lines, five HLF-r lines, and four near haploid lines to further study the mechanisms and therapeutic vulnerabilities of these high-risk B-ALL subtypes. These models provide an important resource for identifying dependencies and therapeutic vulnerabilities."

Preclinical • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • CRLF2 • IKZF1 • KMT2A • MEF2D • NTRK3 • NUTM1 • PAX5 • PBX1 • TCF3 • ZEB2