clofarabine / Generic mfg. - LARVOL DELTA

High event-free (EFS) and overall survival (OS) after non-total body irradiation (TBI) conditioning and allogeneic hematopoietic cell transplantation (HCT) in next-generation-sequencing minimal residual disease (NGS-MRD) negative B-acute lymphoblastic leukemia (B-ALL): Results from the EndRAD trial (PTCTC ONC1701) (ASH 2025) - P2 | "Based upon retrospectivedata showing low rates of relapse, we hypothesized that patients with negative pre-HCT MRD by next-generation-sequencing of IgH B-cell receptor rearrangements (NGS-MRD) could achieve 2-year EFSexceeding 75% with a non-TBI regimen, an outcome comparable to those receiving TBI-based regimens. The Pediatric Transplantation and Cellular Therapy Consortium (PTCTC) conducted a phase IIprospective trial at 45 Centers in North America (ONC1701 EndRAD: NCT03509961) between 2018 and2025 to evaluate outcomes of myeloablative non-TBI conditioning regimens for allogeneic HCT in B-ALLpatients at lower risk for relapse defined by absence of NGS-MRD (Clonoseq) of B-cell receptorrearrangements (BCR) just prior to HCT...Mismatched related/haploidentical grafts received post-transplant cyclophosphamide orTCRαβ/CD19 depletion according to institutional preference...Of patientsenrolled, 33% were White/Non-Hispanic, 37% Hispanic, 12% Black or African American, and..."

Biomarker • Clinical • IO biomarker • Minimal residual disease • Next-generation sequencing • Residual disease • Acute Graft versus Host Disease • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • CNS Disorders • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Transplantation

Haploidentical Donor Transplantation Using a Novel Clofarabine-containing Conditioning Regimen for Very High-risk Hematologic Malignant Neoplasms. (PubMed, J Pediatr Hematol Oncol) - P1; "In a phase I clinical trial (NCT00824135), we substituted clofarabine for fludarabine in a well-established reduced-intensity conditioning regimen for a T cell-depleted, mismatched-related (haploidentical) donor transplant backbone and explored the maximum tolerated dose of clofarabine in this combination in 15 patients undergoing hematopoietic cell transplantation for recurrent/refractory or secondary leukemia. Eleven patients (73.3%) died, with the most common cause of death being disease relapse (in 9 patients [60%]), followed by treatment-related mortality (in 2 patients [13.3%]). Four (26.6%) of the patients are long-term survivors."

Journal • Hematological Disorders • Hematological Malignancies • Hepatology • Leukemia • Oncology • Transplantation

Older Adults with Acute Myeloid Leukemia (AML) Experience Improvement in Health-Related Quality of Life (HRQoL) Scores with Intensive Therapy: Prospective Study from ECOG-ACRIN (EA) E2906 Phase 3 Trial (ASH 2023) - "In the recent EA E2906 phase 3 study of '7&3' (daunorubicin & cytarabine) vs. clofarabine (CLO), a putative lower intensity therapy, we incorporated a prospective patient-reported outcomes (PRO) assessment of HRQoL and fatigue to understand treatment impact from the patients' (pts) perspective. Patient-reported HRQoL & Fatigue was not predictive of completion of protocol therapy. These results serve as a benchmark for expectations with IC in older adults."

Clinical • HEOR • P3 data • Acute Myelogenous Leukemia • Fatigue • Hematological Malignancies • Leukemia • Oncology

Concurrent Recurrent Intracranial Langerhans Cell Histiocytosis and BRAF V600E–Mutated Papillary Thyroid Carcinoma in a Young Adult: Diagnostic and Therapeutic Challenges (SOHO 2026) - "Initial diagnosis followed craniotomy and biopsy of a frontal skull lesion consistent with LCH, after which he completed 12 months of cytarabine therapy with durable remission...He was ultimately initiated on clofarabine therapy, though treatment adherence remained limited by persistent nausea...The coexistence of recurrent LCH and BRAF V600E–mutated PTC raises the possibility of shared MAPK pathway dysregulation and illustrates the diagnostic and therapeutic complexities associated with overlapping rare malignancies. MAPK: mitogenactivated protein kinase."

Clinical • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Papillary Carcinoma • BRAF

Turning off the radical-based chemistry of human ribonucleotide reductase (ACS-Fall 2026) - "Current FDA-approved drugs include the phosphorylated forms of antileukemic nucleoside analogs – cladribine (ClATP), fludarabine (FlUTP), and clofarabine (ClFTP). Here, we use cryo-electron microscopy to determine the structure of human RNR bound to ClATP to determine if the previously observed a-hexamerization is due to ClATP binding in the dATP allosteric activity site. We also investigate the possibility that phosphorylated forms of ClATP could inhibit RNR by binding to the active site and/or the allosteric specificity site that modulates the substrate preference."

Treosulfan or busulfan plus clofarabine as reduced intensity conditioning regimen before allotransplant for adults with myeloid malignancies. (PubMed, Bone Marrow Transplant) - "CloT3 was independently associated with improved OS (p = 0.038), DFS (p = 0.026) and lower RI (p = 0.024). These exploratory results support further prospective studies, particularly in AML patients."

Journal • Acute Graft versus Host Disease • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Oncology • Transplantation

Using a PET Imaging Agent, 18F-Clofarabine (CFA), to Measure Deoxycytidine Kinase Activity in Metastatic Cancer (clinicaltrials.gov) - P1 | N=5 | Terminated | Sponsor: Roberto Vargas | Recruiting ➔ Terminated; Funding unavailable

Biomarker • Trial termination • Oncology

Treosulfan-Based Versus Clofarabine-Based Conditioning Before Donor Hematopoietic Stem Cell Transplant for the Treatment of Myelodysplastic Syndromes or Acute Myeloid Leukemia (clinicaltrials.gov) - P2 | N=23 | Terminated | Sponsor: Fred Hutchinson Cancer Center | Active, not recruiting ➔ Terminated; The study was closed due to the end of funding.

Trial termination • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation • HLA-B • HLA-C • HLA-DQB1 • HLA-DRB1

Ribonucleotide Reductase Inhibition Overcomes FLT3 Inhibitor Resistance in Acute Myeloid Leukemia. (PubMed, bioRxiv) - "Importantly, the therapeutic efficacy of the gilteritinib/clofarabine combination was independently validated in two genetically distinct patient-derived xenograft (PDX) models harboring different NRAS mutations, demonstrating robust reduction of leukemia burden and confirming the generalizability of RNR inhibition in primary FLT3i-resistant AML. Although FLT3 inhibitors (FLT3i) are an important therapeutic advance in FLT3 ITD + AML, resistance commonly develops. We identified ribonucleotide reductase (RNR) as a new key vulnerability in NRAS -driven FLT3i-resistant AML and demonstrated that multiple RNRis, including the FDA-approved agent clofarabine, restore FLT3i sensitivity and enhance antileukemic activity, supporting a clinically actionable combination strategy."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3 • NRAS

Crystal structure of clofarabine (form I), C10H11ClFN5O3, from synchrotron power diffraction data and density functional theory calculations. (PubMed, Acta Crystallogr E Crystallogr Commun) - "The oxolane ring adopts an envelope conformation and the angle between the mean ring planes is 88.4 (2)°, resulting in an l-shaped mol-ecule. The mol-ecules stack along the short a-axis direction, and N-H⋯O, O-H⋯N and N-H⋯N hydrogen bonds link them into a three-dimensional network."

Journal

Study of Clofarabine in Patients With Recurrent or Refractory Langerhans Cell Histiocytosis and LCH-related Disorders (clinicaltrials.gov) - P2 | N=25 | Active, not recruiting | Sponsor: Dana-Farber Cancer Institute | Trial completion date: Jul 2026 ➔ Dec 2026

Trial completion date • Langerhans Cell Histiocytosis

CLINICAL CHARACTERISTICS, TREATMENT OUTCOMES, AND GENETIC PROFILING OF LANGERHANS CELL HISTIOCYTOSIS: A SINGLE-CENTER RETROSPECTIVE STUDY OF 202 PEDIATRIC PATIENTS (EHA 2026) - "First-line vincristine/prednisone-based therapy in 178 patients yielded complete/partial response (AD-B/AD-S) in 134 (75.3%). Targeted therapy (dabrafenib/trametinib) was administered to 56 patients, primarily those with BRAF V600E or MAP2K1 mutations or refractory disease. Disease progression or suboptimal response prompted second-line therapy (cytarabine, cladribine, clofarabine, or FCN-159) in 64 patients...Summary/Conclusion This large pediatric LCH cohort demonstrates diverse clinical presentation and underscores the prognostic and therapeutic relevance of genetic profiling. Risk-stratified and mutation-directed treatment strategies enable favorable long-term remission in most patients, supporting the integration of early molecular testing into routine clinical management to optimize outcomes."

Retrospective data • Hematological Malignancies • Langerhans Cell Histiocytosis • Pediatrics • BRAF • MAP2K1

VENETOCLAX, CLADRIBINE, AND LOW-DOSE CYTARABINE FOR THE TREATMENT OF PH- RELAPSE/REFRACTORY ACUTE LYMPHOBLASTIC LEUKEMIA: AN ANALYSIS OF A PHASE 2 TRIAL (EHA 2026) - "Purine analogs like clofarabine show activity in relapsed/refractory ALL but achieve only 20-40% complete remission rates with remission lasting approximately six months...Of the 8 non-responders to CAV, 1 subsequently achieved remission with chimeric antigen receptor T-cell (CART) therapy, 2 with salvage allogeneic hematopoietic stem cell transplantation (allo-HSCT), 3 received blinatumomab/inotuzumab ozogamicin and 2 received supportive care...Two patients were lost to follow-up. . Summary/Conclusion The CAV regimen appears to be safe and effective in patients with Ph- R/R B-ALL, warranting further clinical validation through larger-scale, randomized controlled trials."

P2 data • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Agranulocytosis • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Cerebral Hemorrhage • Chronic Lymphocytic Leukemia • Granulocytopenia • Infectious Disease • Oncology • Thrombocytopenia

Efficacy and Safety of the CloB2M (Clofarabine Combined With Busulfan and Melphalan) Conditioning Regimen in Allogeneic Hematopoietic Stem Cell Transplantation for Adult Patients With Acute Myeloid Leukemia in First Complete Remission (clinicaltrials.gov) - P=N/A | N=30 | Not yet recruiting | Sponsor: Institute of Hematology & Blood Diseases Hospital, China

New trial • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation

Identification of drug-related cardiovascular risks: A comprehensive analysis using the FAERS database (2004-2024). (PubMed, PLoS One) - "This study showed that some drugs were significantly associated with CVD, and some of them were newly discovered signals. These findings provide a basis for the generation of new hypotheses about the cardiovascular risk of drugs, but the causal relationship needs to be confirmed by further research."

Journal • Retrospective data • Cardiovascular • Oncology

AALL1131: Combination Chemotherapy in Treating Young Patients With Newly Diagnosed High-Risk B Acute Lymphoblastic Leukemia and Ph-Like TKI Sensitive Mutations (clinicaltrials.gov) - P3 | N=5949 | Completed | Sponsor: National Cancer Institute (NCI) | Trial completion date: Oct 2026 ➔ Mar 2026 | Active, not recruiting ➔ Completed

Trial completion • Trial completion date • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Central Nervous System Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • BCR • ETV6 • KMT2A • RUNX1

Clofarabine for relapsed/refractory Langerhans cell (LC) and non-LC histiocytosis. (PubMed, Blood Adv) - P2 | "In conclusion, clofarabine is active and tolerable in children with R/R LCH and warrants further study in patients with non-LC histiocytosis. Further study of clofarabine in these populations is warranted."

Journal • Langerhans Cell Histiocytosis • Oncology

Cord Blood Transplantation in Children and Young Adults With Blood Cancer (clinicaltrials.gov) - P2 | N=71 | Recruiting | Sponsor: Memorial Sloan Kettering Cancer Center

New P2 trial • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Chronic Myeloid Leukemia • Follicular Lymphoma • Graft versus Host Disease • Hematological Malignancies • Hodgkin Lymphoma • Immunology • Indolent Lymphoma • Leukemia • Lymphoma • Myelodysplastic Syndrome • Non-Hodgkin’s Lymphoma • Oncology • Transplantation • KMT2A • TP53

Histiocytic Sarcoma in a Pediatric Patient Successfully Treated With Clofarabine Monotherapy (ASPHO 2026) - "Clofarabine monotherapy induced durable remission in pediatric HS, suggesting efficacy and tolerability in this rare malignancy. Further studies are warranted to define its role in treatment."

Clinical • Monotherapy • Bone Marrow Transplantation • Febrile Neutropenia • Hematological Malignancies • Infectious Disease • Influenza • Langerhans Cell Histiocytosis • Leukemia • Lymphoma • Neutropenia • Pediatrics • Respiratory Diseases • Sarcoma • Solid Tumor • MAP2K1

Beyond the Usual Sites: Gastrointestinal Langerhans Cell Histiocytosis in a Child (ASPHO 2026) - "Given her gastrointestinal involvement and BRAF mutation in peripheral blood, she was started on upfront clofarabine monotherapy... This case highlights the importance of considering LCH in the differential diagnosis of pediatric patients presenting with refractory gastrointestinal symptoms. Cutaneous manifestations frequently occur prior to gastrointestinal symptoms, providing a critical diagnostic clue. Early recognition through colonoscopy with biopsy, immunohistochemistry, and molecular testing is essential for appropriate risk stratification and treatment."

Clinical • Colorectal Cancer • Contact Dermatitis • Immunology • Langerhans Cell Histiocytosis • BRAF • CD1a

Targeting ribonucleotide reductase to overcome FLT3 inhibitor resistance in acute myeloid leukemia (AACR 2026) - "Combination therapy with gilteritinib and clofarabine in both cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) models significantly reduced leukemic burden and prolonged survival compared with either agent alone. In summary, our findings identify RNR as a critical downstream effector of RAS/MAPK signaling and a promising therapeutic target to overcome FLT3i resistance in NRASmut AML. These results provide a strong mechanistic and preclinical rationale for the combined inhibition of FLT3 and RNR as a novel therapeutic strategy to improve outcomes in resistant AML."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • DUSP6 • E2F1 • FLT3 • NRAS • RRM1 • RRM2 • RRM2B

Phase 1 trial of bortezomib and clofarabine combination in adults with refractory solid tumors (AACR 2024) - P1 | "Despite preclinical evidence of synergy, the human equivalent of the efficacious preclinical combination dose could not be achieved clinically, which may account for the lack of antitumor response. Prolonged SD was observed in 3 pts with CRC. PD analyses, including of CTCs and additional cell death biomarkers, are ongoing."

Clinical • P1 data • Colorectal Cancer • Gastrointestinal Cancer • Hematological Malignancies • Myelodysplastic Syndrome • Oncology • Solid Tumor • CTCs

Clofarabine inhibits U87MG glioblastoma cell line proliferation through CD99 signaling pathway (AACR 2024) - "RNAseq analysis of U87MG cells treated with clofarabine and compared to control showed downregulated genes involved in cell cycle regulation and mitosis, while upregulated genes were enriched in extracellular proteins, cell adhesion, locomotion, p53 signaling pathway, and apoptosis. Our data indicates clofarabine as a potential CD99 inhibitor to treat GBM patients."

Preclinical • Acute Lymphocytic Leukemia • Brain Cancer • CNS Tumor • Ewing Sarcoma • Glioblastoma • Hematological Malignancies • Leukemia • Oncology • Sarcoma • Solid Tumor • CD99

Ribonucleotide reductase is a potential therapeutic target in colorectal cancer (AACR 2025) - "In vivo testing on a CRC cell line xenograft confirmed substantial growth inhibition by clofarabine. These results unveil a possible therapeutic opportunity in colorectal cancer."

Colorectal Cancer • Oncology • Solid Tumor • RRM1

Safety and efficacy of clofarabine for preconditioning intervention in patients undergoing allogeneic hematopoietic stem cell transplantation for relapsed/refractory acute lymphoblastic leukemia. (PubMed, Int J Hematol) - "Thrombotic microangiopathy (n = 2), sinusoidal obstruction syndrome/veno-occlusive disease (n = 2), drug-induced cardiomyopathy (n = 1), and organizing pneumonia (n = 1) were also observed but were clinically manageable. Considering the high-risk nature of this cohort, CLO-based PCI followed by HSCT appears to be a feasible treatment strategy with acceptable toxicity, warranting further investigation."

Journal • Acute Graft versus Host Disease • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Cardiomyopathy • Cardiovascular • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Oncology • Pneumonia • Respiratory Diseases • Transplantation