hydroxyurea

P2, N=119, Recruiting, Novartis Pharmaceuticals | Trial completion date: Jun 2026 --> Jan 2025

P3, N=319, Completed, Celgene | Active, not recruiting --> Completed

This case report demonstrates the feasibility and role of combination pre-clinical high throughput screening to aid decision making in high-risk leukaemia. It also demonstrates the role a JAK1/2 inhibitor can have in the palliative setting in select patients with AML.

After transitioning from anagrelide to hydroxyurea and discontinuing bisoprolol, her renal function improved. This case suggests the importance of considering anagrelide as a potential cause of renal dysfunction in patients using this medication. Therefore, renal biopsy, combined with a comprehensive medical history, is crucial for evaluating the etiology of renal injury in such cases.

Most commonly used agents include hydroxyurea, interferon, Janus kinase inhibitors, and hypomethylating agents, though none are disease-modifying. Actionable mutations (NRAS/KRAS, ETNK1) have also been identified, supporting novel agents targeting involved pathways. Preclinical and clinical studies evaluating new drugs (e.g., fedratinib, phase 2) and combinations are detailed.

Eight drugs have been approved by the FDA for HNC, including both generic and commercial forms: bleomycin sulfate, cetuximab (Erbitux), docetaxel (Taxotere), hydroxyurea (Hydrea), pembrolizumab (Keytruda), loqtorzi (Toripalimab-tpzi), methotrexate sodium (Trexall), and nivolumab (Opdivo). The most common drugs to treat HPV-associated OPC under these clinical trials and implemented as well for HPV-negative HNC include cisplatin, nivolumab, cetuximab, paclitaxel, pembrolizumab, 5-fluorouracil, and docetaxel...In this context, we identified most mutated genes found in HPV-associated OPC that can represent potential targets for drug development. These include TP53, PIK3CA, PTEN, NOTCH1, RB1, FAT1, FBXW7, HRAS, KRAS, and CDKN2A.

The propositus was not controlled by hydroxyurea, and JAK2 inhibitors were not tolerated; however, Ropeginterferon-alfa-2b (Ropeg-IFN-α) induced a remission. We report dominantly inherited erythrocytosis secondary to a novel germline JAK2R715T gain-of-function mutation with many but not all comparable molecular features to JAK2V617F PV. We also document a previously unreported inhibitory mechanism of JAK2 signaling by Ropeg-IFN-α.

While anti-platelets and conventional cytoreductive agents, mainly hydroxycarbamide (hydroxyurea), anagrelide and pegylated interferon, remain the cornerstone of treatment, recent research has shed light on the effectiveness of novel therapies that may help improve outcomes. This comprehensive review focuses on the evolving landscape of treatment strategies in ET, with an emphasis on the role of molecular profiling in guiding therapeutic decisions. Besides evidence-based management according to revised IPSET-thrombosis stratification, we also provide specific observations for those patients with CALR-, MPL-mutated and triple-negative ET, as well as cases with high-risk mutations.

P2, N=49, Active, not recruiting, PharmaEssentia | Trial completion date: Apr 2024 --> May 2025

P2, N=17, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Mar 2024 --> Mar 2025 | Trial primary completion date: Mar 2024 --> Mar 2025

Identification of rearranged PDGFRA or PDGFRB is critical because of the exquisite responsiveness of these diseases to imatinib. Pemigatinib was recently approved for patients with relapsed or refractory FGFR1-rearranged neoplasms...Hydroxyurea and interferon-α have demonstrated efficacy as initial treatment and in steroid-refractory cases of HES. Mepolizumab, an interleukin-5 (IL-5) antagonist monoclonal antibody, is approved by the U.S Food and Drug Administration for patients with idiopathic HES. Cytotoxic chemotherapy agents, and hematopoietic stem cell transplantation have been used for aggressive forms of HES and CEL, with outcomes reported for limited numbers of patients. Targeted therapies such as the IL-5 receptor antibody benralizumab, IL-5 monoclonal antibody depemokimab, and various tyrosine kinase inhibitors for MLN-eo-TK, are under active investigation.

Additionally, the type 2 positive allosteric modulator (PAM2) PNU120596 and hydroxyurea (HU) also inhibited the binding. Our studies demonstrate that activation of α7 AChRs has efficacy in inhibiting the SARS-Cov-2 interaction with the ACE2 receptor and in such a way can prevent virus target cell penetration. These studies also help to clarify the consistent efficacy and positive outcomes for utilizing HU in treating COVID-19.

P2, N=132, Completed, Vanderbilt University Medical Center | Active, not recruiting --> Completed

P3, N=126, Active, not recruiting, Sellas Life Sciences Group | Recruiting --> Active, not recruiting

It is derived from the ATR inhibitor VE-821 and recruits the E3 ubiquitin-ligase component cereblon to ATR...This mechanism provokes DNA replication catastrophe and augments anti-leukemic effects of the clinically used ribonucleotide reductase-2 inhibitor hydroxyurea...Treatment of wild-type but not of cereblon knockout cells with Abd110 stalls their proliferation which verifies that ATR elimination is the primary mechanism of Abd110. Altogether, our findings demonstrate specific anti-leukemic effects of an ATR PROTAC.

P2, N=135, Not yet recruiting, European Organisation for Research and Treatment of Cancer - EORTC

To support objective risk/benefit assessment of cytoreductive drugs in PV patients younger than 60 (PV<60), this systematic review and meta-analysis was conducted to evaluate toxicity and disease-related complications in PV<60 treated with interferon alfa (rIFNα) or hydroxyurea (HU)...With acceptable rates of non-fatal toxicity, cytoreductive treatment, particularly with disease-modifying rIFNα, may benefit PV<60. Future randomized trials prioritizing inclusion of PV<60 are needed to establish a long-term benefit of early cytoreductive treatment in these patients.

P=N/A, N=900, Not yet recruiting, New York University

P2, N=21, Active, not recruiting, New York Medical College | Trial primary completion date: Dec 2023 --> Dec 2024

JAK2V617F was strongly associated with thrombosis and worse TFS. Hydroxyurea was the most preferred cytoreductive agent for patients with high thrombosis risk.

Drug therapy is currently not disease-modifying and includes hydroxyurea and hypomethylating agents; a recent phase-3 study (DACOTA) comparing hydroxyurea and decitabine, in high-risk MP-CMML, showed similar overall survival at 23.1 versus 18.4 months, respectively, despite response rates being higher for decitabine (56% vs. 31%). These include systemic inflammatory autoimmune diseases, leukemia cutis and lysozyme-induced nephropathy; the latter requires close monitoring of renal function during leukocytosis and is a potential indication for cytoreductive therapy.

P3, N=220, Recruiting, Italfarmaco | Not yet recruiting --> Recruiting

P4, N=140, Completed, Novartis Pharmaceuticals | Active, not recruiting --> Completed

Autophosphorylation of ATR at the threonine 1989 site was expressed at a greater level in HTB94 cells compared to AG01522 cells at the baseline and in response to hydroxyurea treatment or exposure to 1 Gy of X-rays...Our results indicate that HTB94 cells were likely more efficient in DNA repair than AG01522 cells, specifically via ATR signaling, which inhibited the bystander signal-induced MN formation. This study highlights the significance of DNA repair efficiency in bystander cell responses.

CDK4/6 inhibitor LEE011 treatment alone may not be a suitable treatment option for lymphocytic leukemia; however, our findings in vitro support the combination of LEE011 with chemotherapy drugs to enhance anti-tumor activity in lymphocytic leukemia.

P1/2, N=336, Active, not recruiting, Constellation Pharmaceuticals | Trial primary completion date: Dec 2023 --> Oct 2024

P2, N=3, Terminated, Mayo Clinic | Trial completion date: May 2025 --> Jun 2023 | Active, not recruiting --> Terminated | Trial primary completion date: May 2024 --> Apr 2023; Slow accrual

There was no statistically significant difference in expression of HIF-2α in the group that reached MMR and did not reach MMR, namely 123.45 pg/mg protein and 89.25 pg/mg protein respectively (p 0.718). This study found no statistically significant difference between HIF-2α expression level and MMR achievement of chronic phase CML patients who received HU before IM therapy.

On most recent exam, the patient had no new symptoms or side effects following 3 months of oral hydroxyurea (25 mg/kg/day). Repeat orbital imaging showed no progression of the lesion and the patient will be monitored closely. Here, we report a rare case of isolated orbital indeterminate cell histiocytosis in a young child.

P2, N=46, Recruiting, Forma Therapeutics, Inc. | Trial completion date: Aug 2025 --> Feb 2026 | Trial primary completion date: Oct 2024 --> Jan 2025

P=N/A, N=60, Not yet recruiting, Nationwide Children's Hospital

P2, N=119, Recruiting, Novartis Pharmaceuticals | Trial completion date: Feb 2026 --> Jun 2026 | Trial primary completion date: May 2024 --> Jan 2025

P3; Trial completion date: Dec 2023 --> Mar 2024

P1, N=48, Active, not recruiting, University of Chicago | Trial completion date: Nov 2023 --> Nov 2027 | Trial primary completion date: Nov 2023 --> Nov 2027

In this regard, once-daily low-dose aspirin is advised for all patients and twice daily for low-risk disease. First-line cytoreductive drugs of choice are hydroxyurea and pegylated interferon-α and second-line busulfan. The current review includes specific treatment strategies in the context of extreme thrombocytosis, pregnancy, splanchnic vein thrombosis, perioperative care, and post-essential thrombocythemia MF, as well as new investigational drugs.

P2, N=207, Active, not recruiting, RWTH Aachen University | N=380 --> 207

P2, N=3, Active, not recruiting, Mayo Clinic | Recruiting --> Active, not recruiting | N=33 --> 3

The sterile alpha motif and histidine-aspartate (HD) domain containing protein 1 (SAMHD1) is a deoxynucleoside triphosphate triphosphohydrolase with ara-CTPase activity that confers cytarabine (ara-C) resistance in several haematological malignancies. In SOX11-negative MCL, SOX11-mediated ara-CTPase inhibition could be mimicked by adding the recently identified SAMHD1 inhibitor hydroxyurea. Taken together, our results identify SOX11 as a novel SAMHD1 interaction partner and its first known endogenous inhibitor with potentially important implications for clinical therapy stratification.

Utilising GSDIM super-resolution microscopy, here we investigated the distribution of fluorescently tagged DDR proteins (53BP1, RNF168, MDC1) and γH2AX in U2OS cells treated with γ-irradiation, etoposide, cisplatin, or hydroxyurea. Furthermore, distinct behaviours of DDR proteins were observed under the same treatment. These findings have implications for cancer treatment strategies involving these agents and provide insights into the nanoscale organisation of the DDR.

P1/2, N=48, Not yet recruiting, Haukeland University Hospital

P4, N=60, Completed, Ain Shams University | Recruiting --> Completed | N=30 --> 60 | Trial completion date: Aug 2023 --> Jan 2024

P3, N=300, Recruiting, Merck Sharp & Dohme LLC | Not yet recruiting --> Recruiting