National Stroke Foundation

Rydapt (midostaurin)

The following drug information is obtained from various newswires, published medical journal articles, and medical conference presentations.


Approval Status:

Approved April 2017

Specific Treatments:

FLT3 positive acute myeloid leukemia and mastocytosis

Therapeutic Areas

General Information

Rydapt (midostaurin) is a multikinase inhibitor.

Rydapt is specifically indicated for the following:

  • in combination with standard cytarabine and daunorubicin induction and cytarabine consolidation chemotherapy, for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) who are FLT3 mutationpositive, as detected by a FDA approved test
  • for the treatment of adult patients with aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematological neoplasm (SM-AHN), or mast cell leukemia

Rydapt is supplied as a capsule for oral administration. Recommended Dosage in Acute Myeloid Leukemia: 50 mg orally twice daily with food on Days 8 to 21 of each cycle of induction with cytarabine and daunorubicin and on Days 8 to 21 of each cycle of consolidation with high-dose cytarabine. Recommended Dosage in ASM, SM-AHN, and MCL: 100 mg orally twice daily with food. Continue treatment until disease progression or unacceptable toxicity occurs.

Please see drug label for recommendations for dose modifications in patients with ASM, SM-AHN, and MCL. Monitor patients for toxicity at least weekly for the first 4 weeks, every other week for the next 8 weeks, and monthly thereafter while on treatment.  

Clinical Results

FDA Approval

The FDA approval of Rydapt for FLT3+ AML was based on the Phase III RATIFY (CALGB 10603 [Alliance]) clinical trial, which was conducted in collaboration with the Alliance for Clinical Trials in Oncology and its 13 contributing international cooperative groups. In the trial, 717 newly diagnosed FLT3+ patients who received Rydapt plus chemotherapy experienced significant improvement in overall survival with a 23% reduction in the risk of death compared with chemotherapy alone (p=0.016). Event-free survival (EFS; event defined as no complete remission within 60 days of the start of induction therapy, relapse or death) was significantly higher for Rydapt plus chemotherapy versus chemotherapy alone (median of 8.2 months compared to 3.0 months, p=0.004).

The FDA approval of Rydapt for adult patients with ASM, SM-AHN, or mast cell leukemia was based on two single-arm open-label multicenter trials, including the Phase II study (CPKC412D2201). The efficacy of Rydapt was established on the basis of confirmed complete remission (CR) plus incomplete remission (ICR) by six cycles of treatment per the modified Valent criteria (n=89. This analysis demonstrated an overall response rate of 21%. Efficacy was also assessed in a post-hoc analysis using the 2013 International Working Group-Myeloproliferative Neoplasms Research and Treatment-European Competence Network on Mastocytosis (IWG-MRT-ECNM) consensus criteria (n=115). This assessment estimated complete remission or partial remission rate of 17%.

Side Effects

Adverse effects associated with the use of Rydapt may include, but are not limited to, the following:


  • febrile neutropenia
  • nausea
  • mucositis
  • vomiting
  • headache
  • petechiae
  • musculoskeletal pain
  • epistaxis
  • device-related infection
  • hyperglycemia
  • upper respiratory tract infection


  • nausea
  • vomiting
  • diarrhea
  • edema
  • musculoskeletal pain
  • abdominal pain
  • fatigue
  • upper respiratory tract infection
  • constipation
  • pyrexia
  • headache
  • dyspnea

Mechanism of Action

Rydapt (midostaurin) is a small molecule that inhibits multiple receptor tyrosine kinases. In vitro biochemical or cellular assays have shown that midostaurin or its major human active metabolites CGP62221 and CGP52421 inhibit the activity of wild type FLT3, FLT3 mutant kinases (ITD and TKD), KIT (wild type and D816V mutant), PDGFRα/β, VEGFR2, as well as members of the serine/threonine kinase PKC (protein kinase C) family.  Midostaurin demonstrated the ability to inhibit FLT3 receptor signaling and cell proliferation, and it induced apoptosis in leukemic cells expressing ITD and TKD mutant FLT3 receptors or overexpressing wild type FLT3 and PDGF receptors. Midostaurin also demonstrated the ability to inhibit KIT signaling, cell proliferation and histamine release and induce apoptosis in mast cells. 

Additional Information

For additional information regarding FLT3 positive acute myeloid leukemia and mastocytosis, please visit