Vyxeos (cytarabine/daunorubicin liposomal formulation)

No abstract available

P2, N=75, Completed, University of Nebraska | Active, not recruiting --> Completed | Trial primary completion date: Oct 2024 --> Mar 2024

P=N/A, N=112, Active, not recruiting, Jazz Pharmaceuticals | Recruiting --> Active, not recruiting

P3, N=882, Recruiting, University of Ulm | Trial completion date: Mar 2024 --> Jun 2027 | Trial primary completion date: Mar 2024 --> Jun 2027

P2, N=42, Completed, French Innovative Leukemia Organisation | Recruiting --> Completed | Trial completion date: Sep 2025 --> Dec 2023

This study highlights that lower-intensity therapy of CPX-351 plus venetoclax as induction therapy provides a well-tolerated treatment option in adults with AML deemed unfit for intensive chemotherapy. This trial was registered at www.clinicaltrials.gov as #NCT04038437.

Since 2017, twelve agents have been approved for the treatment of AML subsets: the BCL2 inhibitor venetoclax; the CD33 antibody drug conjugate gemtuzumab ozogamicin; three FLT3 inhibitors (midostaurin, gilteritinib, quizartinib); three IDH inhibitors (ivosidenib and olutasidenib targeting IDH1 mutations; enasidenib targeting IDH2 mutations); two oral hypomethylating agents (oral poorly absorbable azacitidine; fully absorbable decitabine-cedazuridine [latter approved as an alternative to parenteral hypomethylating agents in myelodysplastic syndrome and chronic myelomonocytic leukemia but commonly used in AML]); and CPX-351 (encapsulated liposomal 5:1 molar ratio of cytarabine and daunorubicin), and glasdegib (hedgehog inhibitor)...To achieve optimal results in such a rare and heterogeneous entity as AML requires expertise, familiarity with this rare cancer, and the access to, and delivery of disparate therapies under rigorous supportive care conditions. In this review, we update the standard-of-care and investigational therapies and outline promising current and future research directions.

P2, N=30, Active, not recruiting, University of California, Irvine | Recruiting --> Active, not recruiting | Trial completion date: Sep 2025 --> Jun 2027 | Trial primary completion date: Jun 2024 --> Jun 2025

P2, N=4, Terminated, Case Comprehensive Cancer Center | N=25 --> 4 | Recruiting --> Terminated; Slow Accrual

P2, N=78, Suspended, National Cancer Institute (NCI) | Recruiting --> Suspended

P2, N=13, Active, not recruiting, Case Comprehensive Cancer Center | Trial completion date: Jun 2026 --> Dec 2026 | Trial primary completion date: Jun 2024 --> Dec 2024

P1/2, N=24, Recruiting, Georgetown University | Trial completion date: Aug 2024 --> Aug 2025 | Trial primary completion date: Aug 2024 --> Aug 2025

P1, N=22, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Aug 2025 --> Nov 2025 | Trial primary completion date: Aug 2024 --> Nov 2024

P1, N=18, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial primary completion date: Dec 2024 --> Nov 2025

P1, N=18, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting

P2, N=268, Not yet recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2024 --> Mar 2027 | Trial primary completion date: Sep 2024 --> Mar 2027

P2, N=750, Not yet recruiting, National Cancer Institute (NCI) | Trial completion date: May 2032 --> May 2029 | Trial primary completion date: May 2032 --> May 2029

P1, N=18, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Feb 2027 --> May 2025 | Trial primary completion date: Feb 2027 --> May 2025

P1, N=18, Recruiting, M.D. Anderson Cancer Center | Trial completion date: May 2024 --> Feb 2027 | Trial primary completion date: May 2024 --> Feb 2027

FLT3 inhibitors, gemtuzumab ozogamicin, and CPX-351 have been shown to improve outcomes for specific subsets of patients. Venetoclax (VEN) with a hypomethylating agent (HMA) is the standard-of-care frontline regimen for most older patients, except perhaps for those with an IDH1 mutation where ivosidenib with azacitidine may also be considered...This article focuses on recent updates and ongoing challenges in the management of AML, with a particular focus on the ongoing challenge of secondary AML and considerations regarding the selection of initial therapy in younger patients. An overview of common side effects and toxicities associated with targeted therapies is also presented here, along with recommended strategies to mitigate these risks.

P1/2, N=47, Recruiting, Ohio State University Comprehensive Cancer Center | Suspended --> Recruiting

There has been import of the IDH1 inhibitor ivosidenib, initially approved for AML; the Bcl-2 inhibitor venetoclax and liposomal daunorubicin/cytarabine (CPX-351) are under active investigation as well. Unfortunately, effective treatment of TP53-mutated disease remains elusive, though preliminary evidence suggests improved outcomes with oral decitabine/cedazuridine over parenteral hypomethylating agent monotherapy. Investigational agents with novel mechanisms of action may help expand the repertoire of treatment options for HR-MDS and trials continue to offer a hopeful therapeutic avenue for suitable patients.

P=N/A, N=100, Recruiting, Centre Hospitalier Universitaire de Nice

P2, N=30, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Jun 2024 --> Jun 2025 | Trial primary completion date: Jun 2024 --> Jun 2025

P3, N=1400, Active, not recruiting, Children's Oncology Group | Recruiting --> Active, not recruiting

P1, N=38, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

P2, N=30, Completed, Weill Medical College of Cornell University | Active, not recruiting --> Completed

In pairwise comparisons adjusted for age, HMA + VEN was associated with improved OS vs. 7 + 3 in patients with SF3B1 mutation and improved OS vs. CPX-351 in those with RNA splicing factor mutations. In molecularly defined secondary AML treatment with HMA + VEN might be preferred but could further be guided by co-mutations.

P1/2, N=47, Suspended, Ohio State University Comprehensive Cancer Center | Recruiting --> Suspended | Trial primary completion date: Dec 2023 --> Dec 2024

P2, N=0, Withdrawn, Uwe Platzbecker | N=108 --> 0 | Not yet recruiting --> Withdrawn

Mechanistically, the protective effect of CPX-351 occurred through pathways involving both the host and the intestinal microbiota, namely via the activation of the aryl hydrocarbon receptor-IL-22-IL-10 host pathway and the production of immunomodulatory metabolites by anaerobes. This study reveals how the gut microbiota may contribute to the good safety profile, with a low infection-related mortality, of CPX-351 and highlights how a better understanding of the host-microbiota dialogue may contribute to pave the way for precision medicine in AML.

P2, N=12, Recruiting, Roswell Park Cancer Institute | N=46 --> 12

P2, N=78, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

P3, N=882, Recruiting, University of Ulm

P=N/A, N=108, Recruiting, Jazz Pharmaceuticals | Not yet recruiting --> Recruiting

Here, we review the current in vitro, clinical, and real-world evidence on the use of CPX-351 in patients with AML and mutations in FLT3. Additionally, we review preliminary data from clinical trials and patient case reports that suggest the combination of CPX-351 with FLT3 inhibitors may represent another treatment option for patients with FLT3 mutation-positive AML.

As in AML, FL kinetic profile predicts response and survival in HR-MDS/CMML. A FLD kinetic profile was the only factor independently associated with higher CR/CRi rates and better EFS. These results have to be confirmed on larger cohorts.

Four pts (33%) were refractory to venetoclax (VEN)-based therapy and 3 pts (25%) had previous alloHCT (Table 1)... Combination of cladribine with standard dose of CPX-351 is well tolerated. Cladribine dose 5 mg/m 2 was selected as RP2D. Safety profile does not indicate any significant additional myelosuppression.

Among patients with AML treated with CPX-351, PTPN11 and IDH2 mutations were independently associated with inferior overall survival compared to those without these mutations. The PTPN11 gene is involved in RAS pathway regulation and has also been associated with shorter survival in AML in other studies. Here, mutated SRSF2 was associated with improved survival after CPX-351 induction.

CPX-351 is able to induce good quality remission with high CR rate and MRD negativity, regardless of mutational burden, allowing a high number of elderly AML patients to undergo to HSCT. MRD evaluation has proven to be a strong prognostic tool also in the setting of elderly s-AML and t-AML patients receiving CPX-351. The prognostic value of high risk mutation seems to be less relevant in CPX-351 treated patients.

The use of CPX-351 demonstrated efficacy across subgroups, especially in t-AML and pts without prior HMA exposure, as shown in larger studies. In pts <60 years, even though CRc rates were lower, CPX-351 led to longer mOS in those who achieved CRc and in those who underwent alloSCT compared to pts ≥60 years, although it didn't reach statistical significance in this small cohort. Induction therapy outcomes and treatment-related complications in our study corroborate the data for prior CPX-351 studies.