Midostaurin is a multi-targeted protein kinase inhibitor that has been investigated for the treatment of acute myeloid leukemia (AML), myelodysplastic syndrome ... From Wikipedia, the free encyclopedia Jump to navigationJump to search Other names PKC412, 4'-N-benzoylstaurosporine Molar mass 570.637 g/mol g·mol−1 Midostaurin (sold under the name Rydapt) is a multi-targeted protein kinase inhibitor that has been investigated for the treatment of acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) and advanced systemic mastocytosis. It is a semi-synthetic derivative of staurosporine, an alkaloid from the bacterium Streptomyces staurosporeus. Midostaurin was found to be active against oncogenic CD135 (FMS-like tyrosine kinase 3 receptor, FLT3), in preclinical studies. Clinical trials have primarily focused on relapsed/refractory AML and MDS and have included single agent and combination agent studies. After successful Phase II clinical trials, midostaurin was found to significantly prolong survival of FLT3-mutated AML patients when combined with conventional induction and consolidation therapies in a randomized Phase III clinical trial. On April 28, 2017, midostaurin was approved by the FDA for the treatment of adult patients with newly diagnosed AML who are positive for oncogenic FLT3, in combination with chemotherapy. The drug is approved for use with a companion diagnostic, the LeukoStrat CDx FLT3 Mutation Assay, which is used to detect the FLT3 mutation in patients with AML. Over 95% of patients with adult onset systemic mastocytosis and approximately 40% of children with cutaneous mastocytosis are positive for the D816V c-Kit activating mutation, which renders c-Kit resistant to currently available tyrosine kinase inhibitors. Midostaurin is an investigational treatment in patients with advanced forms of systemic mastocytosis and D816V c-Kit mutation with a subset of patients achieving clinical response. In an open-label study of patients with mastocytosis-related organ damage (89 eligible patients meeting inclusion for the primary efficacy population), midostaurin showed efficacy in patients with advanced systemic mastocytosis, including the highly fatal variant mast cell leukemia.
Apr 28, 2017 ... FDA also approved midostaurin for the treatment of adults with aggressive systemic mastocytosis (SM), SM with associated hematological ... U.S. Food and Drug Administration Search Menu Resources for Information | Approved Drugs On April 28, 2017, the U.S. Food and Drug Administration approved midostaurin (RYDAPT, Novartis Pharmaceuticals Corp.) for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) who are FLT3 mutation-positive (FLT3+), as detected by an FDA-approved test, in combination with standard cytarabine and daunorubicin induction and cytarabine consolidation. The FDA also approved a companion diagnostic, the LeukoStrat CDx FLT3 Mutation Assay (Invivoscribe Technologies Inc.), for use with midostaurin to test patients with AML for the FLT3 mutation. Approval was based on a randomized, double-blind, placebo-controlled trial in 717 patients with previously untreated FLT3+ AML. This trial randomized patients to either placebo or midostaurin 50 mg orally twice daily on days 8-21 of each cycle of induction and consolidation chemotherapy followed by continuous daily midostaurin for up to 12 cycles. The trial demonstrated a statistically significant improvement in overall survival (OS) for patients receiving midostaurin compared with those on the placebo-containing arm (HR 0.77, p=0.016). Common adverse reactions, occurring in at least 20% of patients, included febrile neutropenia, nausea, mucositis, vomiting, headache, petechiae, musculoskeletal pain, epistaxis, device-related infection, hyperglycemia, and upper respiratory tract infection. The most frequent serious adverse reaction was febrile neutropenia, occurring in 16% of patients on both arms.
Aug 19, 2019 ... Midostaurin is an orally administered type III tyrosine kinase inhibitor which in addition to FLT3 inhibits c-kit, platelet-derived growth factor ... US National Library of Medicine National Institutes of Health Search databaseSearch termSearch The new PubMed site will become the default in mid-May. Ther Adv Hematol. 2017 Sep;8(9):245-261. doi: 10.1177/2040620717721459. Epub 2017 Aug 19. Midostaurin: a novel therapeutic agent for patients with FLT3-mutated acute myeloid leukemia and systemic mastocytosis. Gallogly MM1, Lazarus HM1, Cooper BW2. The development of FLT3-targeted inhibitors represents an important paradigm shift in the management of patients with highly aggressive fms-like tyrosine kinase 3-mutated (FLT3-mut) acute myeloid leukemia (AML). Midostaurin is an orally administered type III tyrosine kinase inhibitor which in addition to FLT3 inhibits c-kit, platelet-derived growth factor receptors, src, and vascular endothelial growth factor receptor. Midostaurin is the first FLT3 inhibitor that has been shown to significantly improve survival in younger patients with FLT3-mut AML when given in combination with standard cytotoxic chemotherapy based on the recently completed RATIFY study. Its role for maintenance therapy after allogeneic transplantation and use in combination with hypomethylating agents for older patients with FLT3-mut has not yet been defined. Midostaurin also has recently been shown to have significant activity in systemic mastocytosis and related disorders due to its inhibitory effect on c-kit bearing a D816V mutation. Activation of downstream pathways in both of these myeloid malignancies likely plays an important role in the development of resistance, and strategies to inhibit these downstream targets may be synergistic. Incorporating patient factors and tumor characteristics, such as FLT3 mutant to wild-type allele ratios and resistance mutations, likely will be important in the optimization of midostaurin and other FLT3 inhibitors in the treatment of myeloid neoplasms.
Medscape - Acute myeloid leukemia (AML) and systemic mastocytosis dosing for Rydapt (midostaurin), frequency-based adverse effects, comprehensive ... This site is intended for healthcare professionals Classes: Antineoplastics, Tyrosine Kinase Inhibitor Indicated, in combination with standard cytarabine and daunorubicin induction and cytarabine consolidation chemotherapy, for adults with newly diagnosed acute myeloid leukemia (AML) who are FLT3 mutation-positive, as detected by an FDA-approved test 50 mg PO BID (~q12hr) on Days 8-21 of each cycle of induction with cytarabine and daunorubicin and on Days 8-21 of each cycle of consolidation with high-dose cytarabine Indicated for adults with aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematological neoplasm (SM-AHN), or mast cell leukemia (MCL) 100 mg PO BID (~q12hr) with food Continue treatment until disease progression or unacceptable toxicity Dosage Modifications (ASM, SM-AHN, MCL) ANC <1 x 10^9/L (without MCL) or ANC < 0.5 x 10^9/L with baseline ANC of 0.5-1.5 x 10^9/L Interrupt dosing until ANC ≥1 x 10^9/L, then resume at 50 mg BID; if tolerated, increase to 100 mg BID Discontinue if low ANC persists for >21 days and is suspected to be related to midostaurin Platelet count <50 x 10^9/L (without MCL) or <25 x 10^9/L with baseline of 25-75 x 10^9/L Interrupt dosing until platelet count ≥50 x 10^9/L, then resume at 50 mg BID; if tolerated, increase to 100 mg BID Discontinue if low platelet count persists for >21 days and is suspected to be related to midostaurin Hemoglobin <8 g/L (without MCL) or life-threatening anemia with baseline of 8-10 g/L
What Midostaurin Is Used For: Acute Myeloid Leukemia (AML) that is FLT3- positive; Mast Cell Leukemia (MCL); Aggressive Systemic Mastocytosis (ASM) ... Midostaurin is the generic name for the trade name drug Rydapt. In some cases, health care professionals may use the trade name Rydapt when referring to the generic drug name midostaurin. Drug Type: Midostaurin is a targeted anti-cancer therapy. This medication is classified as a tyrosine kinase inhibitor, more specifically a FLT3 inhibitor. (For more detail, see "How Midostaurin Works" below) Acute Myeloid Leukemia (AML) that is FLT3-positive Aggressive Systemic Mastocytosis (ASM) Systemic Mastocytosis with Associated Hematological Neoplasm (SM-AHN) Note: If a drug has been approved for one use, physicians may elect to use this same drug for other problems if they believe it may be helpful. This drug is given by mouth with food Anti-nausea medications may be given prior to midostaurin Doses are 50 mg to 100 mg twice daily The amount of midostaurin and duration of therapy that you will receive depends on many factors, including your general health or other health problems, the type of cancer or condition you have, and toxicities experienced while on midostaurin. Your doctor will determine your exact dosage and schedule. Important things to remember about the side effects of midostaurin: Most people will not experience all of the midostaurin side effects listed. Midostaurin side effects are often predictable in terms of their onset, duration, and severity. Midostaurin side effects will improve after therapy is complete. Midostaurin side effects may be quite manageable. There are many options to minimize or prevent the side effects of midostaurin.
Learn about RYDAPT treatment for FLT3-positive acute myeloid leukemia (AML)
and 3 types of systemic mastocytosis (SM). See full Prescribing & Safety Info.
Midostaurin is an orally available small molecule inhibitor of FMS-like tyrosine
kinase 3 (FLT3) which is used as an antineoplastic agent in the treatment of
Learn about the mechanism of action of RYDAPT® (midostaurin) capsules in
acute myeloid leukemia. See full Prescribing & Safety Info.
Aug 15, 2017 ... Midostaurin is also used to certain types of mastocytosis (a blood disorder in
which there are too many mast cells [a certain kind of white blood ...