Crenolanib is an investigational, orally administered medication. It is a type I kinase inhibitor designed to target specific pathways involved in cancer cell growth and survival.
Targeting Specific Cancers
Crenolanib functions as a targeted therapy, interfering with specific molecules involved in cancer growth. It inhibits proteins known as kinases, particularly FMS-like tyrosine kinase 3 (FLT3) and platelet-derived growth factor receptor (PDGFR) isoforms alpha and beta. Kinases are enzymes that play a significant role in cell proliferation, differentiation, and survival by regulating signaling pathways.
FLT3 is a receptor tyrosine kinase. Mutations in its gene, such as internal tandem duplications (ITD) and tyrosine kinase domain (TKD) mutations, are frequently observed in certain cancers, particularly acute myeloid leukemia (AML). These mutations lead to the continuous activation of the FLT3 protein, causing uncontrolled cell growth. Crenolanib blocks these mutated FLT3 signals, including those that confer resistance to other FLT3 inhibitors.
Conditions Where Crenolanib is Used
Crenolanib’s primary focus is for the treatment of acute myeloid leukemia (AML), especially in patients who have FLT3 gene mutations. These FLT3 mutations, particularly ITDs, are found in approximately 30% of AML cases and are linked to a less favorable outlook and higher rates of relapse following standard chemotherapy. Identifying these FLT3 mutations through genetic testing is important because it helps determine if crenolanib might be a suitable treatment option.
Crenolanib has shown activity against both FLT3-ITD and FLT3-TKD mutations, including the D835 point mutations that can lead to resistance to other FLT3 inhibitors. Beyond AML, crenolanib is also being investigated in clinical trials for other cancers, such such as gastrointestinal stromal tumors (GIST) with specific PDGFRα mutations and gliomas.
Receiving Crenolanib Treatment
Crenolanib is typically administered orally, making it a convenient option for patients. In clinical trials for newly diagnosed FLT3-mutated AML, crenolanib has been given at a dose of 100 mg three times daily, starting from day 9 of chemotherapy induction and continuing after consolidation or transplant for up to 12 months.
Patients undergoing treatment with crenolanib may experience various side effects, which are carefully monitored by healthcare professionals. Common adverse events include diarrhea, nausea, vomiting, and febrile neutropenia. Other reported side effects include peripheral edema, liver dysfunction, and rash. While most adverse events are manageable, some patients may require dose reductions or temporary discontinuation of the medication due to toxicity. Regular monitoring of blood counts, liver function, and other parameters helps healthcare providers manage these potential side effects and ensure patient safety throughout the treatment course.
Current Research and Availability
Crenolanib is currently an investigational product, meaning it has not yet received full approval for sale in the United States by the Food and Drug Administration (FDA). However, it has been granted Fast Track designation by the FDA for the treatment of FLT3 mutation-positive relapsed or refractory acute myeloid leukemia. This designation is given to drugs that address serious conditions and have the potential to fill an unmet medical need, aiming to expedite their development and review.
Crenolanib has been evaluated in multiple clinical trials across various phases, including phase 1 and phase 2 studies, for both newly diagnosed and relapsed/refractory AML patients with FLT3 mutations. A phase 3 randomized study comparing crenolanib to midostaurin, another FLT3 inhibitor, in newly diagnosed FLT3-mutated AML patients is currently underway.