Qinprezo (vosaroxin)

Molecular docking, molecular dynamics (MD) simulations, and MM/GBSA calculations further confirmed the stable binding of voreloxin to both c-Myc and Bcl-2 G4s, primarily driven by π-π stacking and hydrogen bonding interactions. These findings provide valuable insights for the development of G4-targeting drugs for cancer therapy.

P2/3, N=3100, Recruiting, University Hospital, Angers

P2, N=42, Active, not recruiting, Vanderbilt-Ingram Cancer Center | Trial completion date: Apr 2024 --> Sep 2024

P1, N=35, Completed, Washington University School of Medicine | Active, not recruiting --> Completed

P2, N=42, Active, not recruiting, Vanderbilt-Ingram Cancer Center | Trial completion date: Jan 2024 --> Apr 2024

Quinolones, antibacterials that attack DNA gyrase and topoisomerase IV (functional analog of mammalian Top2), possess a broad spectrum chemotherapeutic activities including anti-leukemic effects (e. g. vosaroxin)...Whereas, WAC did neither increase serum troponin-T nor decrease the crypt numbers in the small intestine, indicating WAC was less toxic than doxorubicin...R-WAC and cytarabine or daunorubicin and cytarabine did not exhibited decreased body weight in mice...ConclusionR-WAC has promising anti-leukemia effects with less toxicities compared with conventional anthracycline possibly due to the different inhibitory mechanisms of Top2 isoform (anthracycline inhibits Top2β). These results indicate that R-WAC is a promising therapeutic agent for AML and support its clinical development, especially as a combination of R-WAC with cytarabine or venetoclax.

P2, N=42, Active, not recruiting, Vanderbilt-Ingram Cancer Center | Trial completion date: Jul 2023 --> Jan 2024

P2, N=42, Active, not recruiting, Vanderbilt-Ingram Cancer Center | Trial completion date: Jul 2022 --> Jul 2023

Treatments included: Low dose Ara-C (LDAC) alone, sapacitabine alone and LDAC in combination with vosaroxin, tosedostat or ganetespib (MRC/NCRI); Azacytidine (AZA) alone, tipifarnib alone, and AZA in combination with mylotarg, midostaurin, and nivolumab (SWOG). Our ability to predict early death in older patients treated with lower intensity AML therapies is limited with routinely available clinical variables. Inclusion of cytogenetic risk, FLT3-ITD, and NPM1 mutation status minimally improved the prognostic accuracy as did some of the QLQ-C30 subscales. Our data highlight the difficulties in predicting outcomes with non-intensive AML therapy with routinely available baseline clinical information.

P2, N=42, Active, not recruiting, Vanderbilt-Ingram Cancer Center | Trial completion date: Jul 2021 --> Jul 2022

The trial design includes several randomizations (R): Idarubicin vs daunorubicin for induction (R1), HDAC vs IDAC for consolidation (R2), post-transplant GVHD prophylaxis modalities (R3). The phase 3 part of the trial will not open. The BIG-1 trial is still ongoing and uses the same design to tests addition of other drugs to the IDAC/HDAC consolidation backbone.

P2, N=42, Active, not recruiting, Vanderbilt-Ingram Cancer Center | Trial completion date: Jul 2020 --> Jul 2021

Vosaroxin and venetoclax synergistically induce apoptosis in acute myeloid leukemia cells and cooperatively target acute myeloid leukemia progenitor cells while sparing normal hematopoietic progenitor cells. Our results support the clinical testing of vosaroxin in combination with venetoclax for treating patients with acute myeloid leukemia, especially in the elderly population.