This trial is evaluating whether MBG453 will improve 1 primary outcome and 5 secondary outcomes in patients with Myelodysplastic Syndromes. Measurement will happen over the course of 6 months.
This trial requires 20 total participants across 2 different treatment groups
This trial involves 2 different treatments. MBG453 is the primary treatment being studied. Participants will all receive the same treatment. There is no placebo group. The treatments being tested are in Phase 2 and have already been tested with other people.
The most commonly prescribed drug for patients with MDS is cytarabine; the most commonly used agent in childhood cases is the anthracycline regimen of doxorubicin plus daunorubicin.
The overall number of new cases of MDS, the MDS sub-trend and the number of new MDS sub-trend cases remain unclear. Future studies should determine when the current trend in the absolute number of MDS cases will change, and the relative sub-trend number of MDS cases may fluctuate in the future.
Overall survival for patients with indolent MDS is > 50%; although patients with refractoriness to cytotoxic or tyrosine kinase inhibitor therapy have a poor prognosis. Further studies are needed to elucidate causes of death and to delineate risks of therapy in patients with non-indolent MDS.
It is likely that there are multiple molecular pathways to myelodysplastic syndromes. However, as the molecular mechanisms become better understood, we may eventually have a means of classifying myelodysplastic syndromes as distinct malignancies.
The diagnosis of MDS usually does not require a bone marrow examination to make a correct diagnosis. Patients have a history of prolonged bleeding, bruising, and/or weakness, and often show signs of anemia of the gastrointestinal tract. Symptoms usually require more than 2 years to develop before the diagnosis is made. As MDS progresses, symptoms emerge, including blood or marrow malignancies, thromboses, or abnormal bleeding from the gastrointestinal or the brain. Bone marrow analyses frequently demonstrate myeloid blast cells, which may have specific associations with disease severity and progression.
Myelodysplastic syndromes are a group of blood cancers that most commonly affect infants and young children. They can be subclassified into different groups based on clinical and genetic features: the favorable-, intermediate-, and unfavorable-related types. Favorable-related cases have a normal or low risk for cancer relapse and an excellent prognosis. Clinically, they are also characterized by a specific morphology (immature granulocyte) and a characteristic cytogenetic profile.
[MBG453 is a novel MEK1 inhibitor being developed for the treatment of patients with refractory MDS, and for the treatment of refractory systemic mastocytosis. This drug has been found to induce rapid and durable responses in patients with relapsed or refractory disease. Current Phase II and III trials are ongoing.
[About 50/100,000 of MDS patients die annually from either hematological causes, such as infections, bleeding, or malignancies, or because of complications related MDS, such as congestive heart failure or respiratory infections] (source needed, and it can be searched using Power\n\nThe latest (and the second-most powerful) clinical trial database is PowerRun.\n(http://www.powerrun.com).
The study found that intravenous MG453 may be more effective than a placebo plus methylprednisolone (3 mg. d, 3 times/day) for people with an refractory MDS.
This work establishes Mbg453 as a new inhibitor of Mdm2/Mdmx and provides insights into how the Drosophila proteins are regulated by cell- and cell-signal proteins in the cytoplasm.
Myelodysplastic syndromes are rare. The prognosis is good with early diagnosis and treatment with cytarabine plus dexamethasone. In a review of MDS patients by the Cancer and Leukaemia Group of the UK National AML-AML-BSC Study, the median time to first chemotherapy was 41 days and the median survival time was 26 days, with an expected survival of 15 months after diagnosis but more than 40 months (95% CI 30, to 40 months) for patients without a marrow transplant. In one study of the Italian SICMMA database of patients treated between 1991 and 2007, the median rate of disease-free survival was 13% and the median OS was 9.
To obtain appropriate data to better characterize the incidence of MDS, the authors need to identify an appropriate study population and a suitable and practical definition of MDS. It is important to determine the average patient age at onset in order to establish appropriate diagnostic criteria. In a recent study, findings obtained in this study indicate that younger patients are more likely to have a lower risk/advanced MDS phenotype (i.e., AML, CMML etc.).