CLINICAL TRIALS PROFILE FOR MIDOSTAURIN

All Clinical Trials for midostaurin

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00045942 ↗	PKC412 in Participants With Acute Myeloid Leukemia or With Myelodysplastic Syndrome (CPKC412A2104 Core); and PKC412 in Participants With Acute Myeloid Leukemia or With Myelodysplastic Syndrome With Either Wild Type or Mutated FMS-like Tyrosine Kinas	Completed	Dana-Farber Cancer Institute	Phase 1/Phase 2	2002-01-30	CPKC412A2104 core had a 2 stage design. In stage 1, eight participants were treated. If at least one participant showed a clinical response, four more participants were recruited to stage 2. The trial was to be stopped if no participants showed a response in stage 1. POC was achieved if at least 2 participants out of 12 responded. In PKC412A2104E1, participants with AML or high risk MDS with wild-type or mutant FTL3 who had not previously received a FLT3 inhibitor were randomized to receive continuous twice daily oral doses of either 50 or 100 mg midostaurin in 1 28-day cycle regimen. Participants were to be treated until disease progression or the occurrence of unacceptable treatment-related toxicity. PKC412A2104 E2 contained 2 dosing regimens: 1) intra-participant midostaurin dose escalation and 2) midostaurin with itraconazole in participants with AML and high risk MDS irrespective of FLT3 status. Eligible participants were alternately assigned to the regimens. At the Investigator's discretion, intra-participant dose escalation was allowed for any previously enrolled CPKC412A2104E1 participant receiving midostaurin at the time of the approval of amendment 4. Participants were treated until the time of disease progression.
NCT00045942 ↗	PKC412 in Participants With Acute Myeloid Leukemia or With Myelodysplastic Syndrome (CPKC412A2104 Core); and PKC412 in Participants With Acute Myeloid Leukemia or With Myelodysplastic Syndrome With Either Wild Type or Mutated FMS-like Tyrosine Kinas	Completed	Memorial Sloan Kettering Cancer Center	Phase 1/Phase 2	2002-01-30	CPKC412A2104 core had a 2 stage design. In stage 1, eight participants were treated. If at least one participant showed a clinical response, four more participants were recruited to stage 2. The trial was to be stopped if no participants showed a response in stage 1. POC was achieved if at least 2 participants out of 12 responded. In PKC412A2104E1, participants with AML or high risk MDS with wild-type or mutant FTL3 who had not previously received a FLT3 inhibitor were randomized to receive continuous twice daily oral doses of either 50 or 100 mg midostaurin in 1 28-day cycle regimen. Participants were to be treated until disease progression or the occurrence of unacceptable treatment-related toxicity. PKC412A2104 E2 contained 2 dosing regimens: 1) intra-participant midostaurin dose escalation and 2) midostaurin with itraconazole in participants with AML and high risk MDS irrespective of FLT3 status. Eligible participants were alternately assigned to the regimens. At the Investigator's discretion, intra-participant dose escalation was allowed for any previously enrolled CPKC412A2104E1 participant receiving midostaurin at the time of the approval of amendment 4. Participants were treated until the time of disease progression.
NCT00045942 ↗	PKC412 in Participants With Acute Myeloid Leukemia or With Myelodysplastic Syndrome (CPKC412A2104 Core); and PKC412 in Participants With Acute Myeloid Leukemia or With Myelodysplastic Syndrome With Either Wild Type or Mutated FMS-like Tyrosine Kinas	Completed	University of California, Los Angeles	Phase 1/Phase 2	2002-01-30	CPKC412A2104 core had a 2 stage design. In stage 1, eight participants were treated. If at least one participant showed a clinical response, four more participants were recruited to stage 2. The trial was to be stopped if no participants showed a response in stage 1. POC was achieved if at least 2 participants out of 12 responded. In PKC412A2104E1, participants with AML or high risk MDS with wild-type or mutant FTL3 who had not previously received a FLT3 inhibitor were randomized to receive continuous twice daily oral doses of either 50 or 100 mg midostaurin in 1 28-day cycle regimen. Participants were to be treated until disease progression or the occurrence of unacceptable treatment-related toxicity. PKC412A2104 E2 contained 2 dosing regimens: 1) intra-participant midostaurin dose escalation and 2) midostaurin with itraconazole in participants with AML and high risk MDS irrespective of FLT3 status. Eligible participants were alternately assigned to the regimens. At the Investigator's discretion, intra-participant dose escalation was allowed for any previously enrolled CPKC412A2104E1 participant receiving midostaurin at the time of the approval of amendment 4. Participants were treated until the time of disease progression.
NCT00045942 ↗	PKC412 in Participants With Acute Myeloid Leukemia or With Myelodysplastic Syndrome (CPKC412A2104 Core); and PKC412 in Participants With Acute Myeloid Leukemia or With Myelodysplastic Syndrome With Either Wild Type or Mutated FMS-like Tyrosine Kinas	Completed	Weill Medical College of Cornell University	Phase 1/Phase 2	2002-01-30	CPKC412A2104 core had a 2 stage design. In stage 1, eight participants were treated. If at least one participant showed a clinical response, four more participants were recruited to stage 2. The trial was to be stopped if no participants showed a response in stage 1. POC was achieved if at least 2 participants out of 12 responded. In PKC412A2104E1, participants with AML or high risk MDS with wild-type or mutant FTL3 who had not previously received a FLT3 inhibitor were randomized to receive continuous twice daily oral doses of either 50 or 100 mg midostaurin in 1 28-day cycle regimen. Participants were to be treated until disease progression or the occurrence of unacceptable treatment-related toxicity. PKC412A2104 E2 contained 2 dosing regimens: 1) intra-participant midostaurin dose escalation and 2) midostaurin with itraconazole in participants with AML and high risk MDS irrespective of FLT3 status. Eligible participants were alternately assigned to the regimens. At the Investigator's discretion, intra-participant dose escalation was allowed for any previously enrolled CPKC412A2104E1 participant receiving midostaurin at the time of the approval of amendment 4. Participants were treated until the time of disease progression.
NCT00045942 ↗	PKC412 in Participants With Acute Myeloid Leukemia or With Myelodysplastic Syndrome (CPKC412A2104 Core); and PKC412 in Participants With Acute Myeloid Leukemia or With Myelodysplastic Syndrome With Either Wild Type or Mutated FMS-like Tyrosine Kinas	Completed	Novartis Pharmaceuticals	Phase 1/Phase 2	2002-01-30	CPKC412A2104 core had a 2 stage design. In stage 1, eight participants were treated. If at least one participant showed a clinical response, four more participants were recruited to stage 2. The trial was to be stopped if no participants showed a response in stage 1. POC was achieved if at least 2 participants out of 12 responded. In PKC412A2104E1, participants with AML or high risk MDS with wild-type or mutant FTL3 who had not previously received a FLT3 inhibitor were randomized to receive continuous twice daily oral doses of either 50 or 100 mg midostaurin in 1 28-day cycle regimen. Participants were to be treated until disease progression or the occurrence of unacceptable treatment-related toxicity. PKC412A2104 E2 contained 2 dosing regimens: 1) intra-participant midostaurin dose escalation and 2) midostaurin with itraconazole in participants with AML and high risk MDS irrespective of FLT3 status. Eligible participants were alternately assigned to the regimens. At the Investigator's discretion, intra-participant dose escalation was allowed for any previously enrolled CPKC412A2104E1 participant receiving midostaurin at the time of the approval of amendment 4. Participants were treated until the time of disease progression.
NCT00093600 ↗	PKC412, Daunorubicin, and Cytarabine in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia	Completed	Novartis Pharmaceuticals	Phase 1	2004-02-01	RATIONALE: PKC412 may stop the growth of cancer cells by blocking the enzymes necessary for their growth. It may also increase the effectiveness of daunorubicin and cytarabine by making cancer cells more sensitive to the drugs. Drugs used in chemotherapy, such as daunorubicin and cytarabine, work in different ways to stop cancer cells from dividing so they stop growing or die. Combining PKC412 with chemotherapy may kill more cancer cells. PURPOSE: This phase I trial is studying the side effects and best way to give PKC412 when given either after or together with daunorubicin and cytarabine in treating patients with newly diagnosed acute myeloid leukemia.

Clinical Trial Conditions for midostaurin

Condition Name

Condition Name for midostaurin
Intervention	Trials
Acute Myeloid Leukemia	21
Myelodysplastic Syndrome	5
Leukemia	5
Secondary Acute Myeloid Leukemia	4

Condition MeSH

Condition MeSH for midostaurin
Intervention	Trials
Leukemia, Myeloid, Acute	39
Leukemia	35
Leukemia, Myeloid	34
Myelodysplastic Syndromes	11

Clinical Trial Locations for midostaurin

Trials by Country

Trials by Country for midostaurin
Location	Trials
United States	220
Italy	58
Japan	33
Germany	18
Spain	13

Trials by US State

Trials by US State for midostaurin
Location	Trials
Massachusetts	16
California	14
Florida	9
Texas	9
Michigan	9

Clinical Trial Progress for midostaurin

Clinical Trial Phase

Clinical Trial Phase for midostaurin
Clinical Trial Phase	Trials
PHASE1	2
Phase 3	6
Phase 2/Phase 3	1

Clinical Trial Status

Clinical Trial Status for midostaurin
Clinical Trial Phase	Trials
Completed	17
Recruiting	15
Active, not recruiting	6

Clinical Trial Sponsors for midostaurin

Sponsor Name

Sponsor Name for midostaurin
Sponsor	Trials
Novartis Pharmaceuticals	21
National Cancer Institute (NCI)	8
Novartis	4

Sponsor Type

Sponsor Type for midostaurin
Sponsor	Trials
Other	50
Industry	35
NIH	8

Midostaurin: Clinical Trials Update, Market Analysis, and Future Projections

Last updated: October 28, 2025

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Introduction

Midostaurin (marketed as Rydapt), developed by Novartis, is a multikinase inhibitor initially approved by the FDA in 2017 for the treatment of FLT3-mutated acute myeloid leukemia (AML) and advanced systemic mastocytosis. Its mechanism of action involves inhibiting multiple kinases involved in tumor cell proliferation and survival. The drug's clinical development trajectory, evolving indications, and market dynamics are critical for stakeholders aiming to gauge future opportunities and competitive positioning.

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Clinical Trials Landscape

Current Status and Ongoing Studies

Since its initial approval, Midostaurin’s clinical development has expanded into various hematologic malignancies beyond AML. As of the latest update in 2023, several trials are ongoing, exploring efficacy, safety, and new therapeutic combinations:

• AML Treatment in Combination Regimens: Several Phases II and III trials examine Midostaurin combined with chemotherapies to enhance response rates. For instance, trials like NCT02997202 investigate its use with low-dose cytarabine in elderly AML patients.

• Systemic Mastocytosis: Newer studies focus on relapsed or refractory aggressive systemic mastocytosis and mast cell leukemia, expanding the drug’s therapeutic scope. NCT03969391 investigates Midostaurin in adult patients with advanced systemic mastocytosis.

• FLT3-Positive Leukemia Maintenance Therapy: Extended research, such as the RADIUS trial (NCT03626513), examines Midostaurin as a maintenance therapy post-chemotherapy or stem cell transplant in FLT3-mutated AML.

• Other Hematologic Malignancies: Investigations include its role in myelodysplastic syndromes and other kinase-driven disorders, although these are at earlier phases.

Key Trial Outcomes

Data from pivotal trials underpin regulatory approvals:

• The 2017 FDA approval of Midostaurin for AML was based on the RATIFY trial, a Phase III study demonstrating a significant improvement in overall survival (OS) and event-free survival (EFS) when combined with standard chemotherapy in FLT3-mutated AML patients. The median OS improved from 25.6 months with chemotherapy alone to 74.7 months with the addition of Midostaurin [1].

• For systemic mastocytosis, Phase II data indicate notable symptom improvement and disease control, leading to regulatory recognition of its efficacy in this indication.

Regulatory Developments

Ongoing clinical data influence regulatory status, with some regions considering expanded approvals for indications like systemic mastocytosis and combinations with other therapies. The evolving clinical evidence positions Midostaurin either to maintain or expand its market exclusivity as new approvals are granted.

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Market Analysis

Global Market Size and Trends

The hematologic cancer therapeutics market, into which Midostaurin primarily competes, was valued at approximately USD 13.2 billion in 2022 and is projected to grow at a CAGR of around 7.2% over the next five years (IQVIA, 2022). AML remains a significant segment within this space, driven by unmet needs in refractory cases and newly diagnosed elderly populations.

Key Market Drivers

• Increasing Incidence of FLT3 Mutations: AML with FLT3 mutations accounts for roughly 30% of AML cases globally, translating into a substantial patient subset eligible for Midostaurin treatment.

• Growing Use of Targeted Therapies: Increased adoption of molecular profiling facilitates the selection of patients with FLT3 mutations, expanding the potential market share.

• Approval Expansion: The potential for Midostaurin to be approved for additional indications, such as systemic mastocytosis and combination regimens, broadly increases its commercial footprint.

• Reimbursement Landscape: Favorable reimbursement scenarios in major markets like the US, EU, and Japan are supporting access to Midostaurin, although differences exist depending on healthcare policies.

Competitive Environment

Midostaurin faces competition from newer, more selective FLT3 inhibitors like Gilteritinib (Astellas/Fujifilm), which was approved in 2018 for relapsed/refractory FLT3-mutated AML, offering a different line of therapy with potentially superior efficacy [2]. However, Midostaurin maintains a strong position in front-line treatment due to its demonstrated survival benefits when combined with chemotherapy.

Market Challenges

• Resistance Development: Emerging data suggest some AML patients develop resistance, limiting long-term efficacy, prompting combination strategies or next-generation kinase inhibitors.

• Pricing and Cost-Effectiveness: High drug prices combined with the complexity of treatment regimens pose reimbursement and affordability challenges.

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Future Market Projections

Growth Opportunities

• Indication Expansion: Approval for systemic mastocytosis and other kinase-driven disorders could add considerable revenue streams.

• Combination Therapies: Incorporating Midostaurin into combination regimens for AML and other hematological malignancies is expected to improve outcomes, thus expanding its therapeutic role.

• Biomarker-Driven Approaches: Increasing use of advanced diagnostics to identify FLT3 and other kinase mutations will refine patient selection, driving sales and clinical outcomes.

Forecasted Revenue

Based on current adoption rates, clinical trial outcomes, and regulatory developments, Midostaurin’s global sales are projected to reach USD 600–800 million annually by 2026, contingent upon successful indication expansions and market penetration strategies (MarketWatch, 2022).

Emerging Trends

• Personalized Medicine: The trend towards precision oncology will favor targeted agents like Midostaurin, especially as molecular profiling becomes standard in AML management.

• Digital Health Integration: Enhanced monitoring of treatment response through digital platforms may optimize therapy adherence and outcomes.

• Competitive Landscape Shifts: Next-generation kinase inhibitors and combination strategies may influence market share, necessitating continuous R&D investments.

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Conclusion

Midostaurin remains a vital agent in the management of FLT3-mutated AML, bolstered by significant clinical trial data demonstrating survival benefits. Its expanding therapeutic indications, coupled with ongoing clinical research, suggest sustainable growth prospects. However, competitive pressures from newer agents and resistance challenges require strategic positioning through indication expansion, combination therapies, and personalized treatment approaches.

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Key Takeaways

• Clinical Evidence: The RATIFY trial remains a benchmark, confirming Midostaurin’s efficacy as a front-line AML therapy, especially in FLT3-mutated cases.

• Market Potential: Growing indications, combination regimens, and personalized medicine trends underpin promising revenue trajectories, projected to reach USD 600–800 million annually by 2026.

• Competitive Strategy: Continuous R&D, clinical trial expansion, and regulatory engagement are essential to maintain market relevance amid emerging competitors like Gilteritinib.

• Regulatory Outlook: Potential approvals for systemic mastocytosis and other indications could significantly widen Midostaurin’s market scope.

• Challenges: Resistance development, high costs, and competition necessitate proactive strategies to sustain growth.

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FAQs

1. Will Midostaurin’s approval expand to other hematologic malignancies?
Clinical trials are evaluating its efficacy in conditions like systemic mastocytosis, MDS, and other kinase-driven disorders, which could lead to regulatory approvals in these areas.

2. How does Midostaurin compare to newer FLT3 inhibitors like Gilteritinib?
While Gilteritinib offers benefits in relapsed/refractory AML, Midostaurin remains preferred in frontline therapy due to proven survival advantages in combination with chemotherapy, particularly in FLT3-mutated AML.

3. What are the main challenges facing Midostaurin’s market growth?
Emerging resistance, competition from more selective agents, high costs, and the need for precise biomarker-driven patient selection are key hurdles.

4. Are there ongoing trials exploring combination therapies including Midostaurin?
Yes. Trials like NCT02997202 examine combinations with chemotherapies and targeted agents to enhance efficacy and address resistance.

5. What is the potential impact of personalized medicine on Midostaurin’s market?
Increased use of molecular diagnostics will enable more targeted patient selection, improving response rates and market penetration, especially as indications expand.

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References

[1] Stone RM, et al. "Midostaurin plus chemotherapy for acute myeloid leukemia with FLT3 mutations." N Engl J Med, 2017;377(5):454-464.
[2] Perl AE, et al. "Gilteritinib or chemotherapy for relapsed or refractory FLT3-mutated AML." N Engl J Med, 2019;381(18):1728-1740.