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Trial to Assess the Efficacy of Midostaurin (PKC412) in Patients With c-KIT or FLT3-ITD Mutated t(8;21) AML (MIDOKIT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01830361
Recruitment Status : Completed
First Posted : April 12, 2013
Last Update Posted : August 6, 2020
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Technische Universität Dresden

Brief Summary:
To assess the efficacy of tyrosine-kinase inhibitor midostaurin in c-KIT or FLT3-ITD mutated t(8;21) AML. To assess the efficacy of midostaurin depending on the type of c-KIT mutation

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Drug: midostaurin (PKC412) Phase 2

Detailed Description:

AML patients displaying t(8;21) have a relatively favourable outcome. Nevertheless, only approximately 50% of patients carrying this cytogenetic aberration are alive at 5 years. This suggests that some patients have more aggressive leukemic phenotypes and indicates the need for treatment optimization with novel therapies.

The mutated KIT gene as well as the FLT3-ITD mutation have recently been identified as factors most likely to explain the heterogeneous clinical outcomes within the group of t(8;21) AML. The FLT3 and c-KIT genes encode type III receptor tyrosine kinases (RTK) with important and partly redundant functions in early hematopoietic stem cells. Various activating mutations have been described for both genes. For c-KIT, the incidence ranges from 17 to 48% depending on the source population and type of mutations determined. It has been consistently shown that in AMLs with t(8;21), mutated c-KIT is associated with a dramatically increased risk of relapse and reduced overall survival compared to their unmutated counterparts. The FLT3-ITD mutation has a similar negative effect on prognosis in the patient group of t(8;21) mutated AMLs as c-KIT.

PKC412 (midostaurin) is known to inhibit the c-KIT RTK activity as well as the FLT3 kinase, both in patients with ITD and TKD mutations. It should therefore be possible to abrogate the negative impact of pathologically increased c-KIT or FLT3-ITD activity on relapse and overall survival by using midostaurin in this patient population. Aim of the proposed clinical trial is to prove the efficacy of midostaurin in c-KIT or FLT3-ITD mutated t(8;21)- AMLs in an open-label one-arm design.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 18 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Single-arm Phase II Trial to Assess the Efficacy of Midostaurin (PKC412) Added to Standard Primary Therapy in Patients With Newly Diagnosed c-KIT or FLT3-ITD Mutated t(8;21) AML
Actual Study Start Date : March 13, 2013
Actual Primary Completion Date : October 30, 2019
Actual Study Completion Date : October 30, 2019

Arm Intervention/treatment
Experimental: midostaurin (PKC412), capsules
midostaurin 50 mg (two 25 mg capsules) is given in combination with the second of two induction cycles and in combination with three cycles of high-dose cytarabine (HiDAC) consolidation chemotherapies and maintenance treatment in patients with c-kit or FLT3-ITD positive t(8;21) AML in an open-label one-arm design. The first cycle of induction is not part of the study.
Drug: midostaurin (PKC412)
Midostaurin 50 mg (2 capsules) twice daily days 8-21 in induction II + consolidation I-III; maintenance treatment twice daily continuously for 12 months
Other Name: Rydapt

Primary Outcome Measures :
  1. Event-free Survival [ Time Frame: 2-year Event-free Survival ]

Secondary Outcome Measures :
  1. Time to relapse [ Time Frame: 2-years ]
  2. Overall survival [ Time Frame: 2-years ]
  3. Relapse-free survival [ Time Frame: 2-years ]
  4. morphologic and molecular CR rate [ Time Frame: 2-years ]
  5. incidence of AEs/SAEs [ Time Frame: until 30 days after end of treatment ]
  6. MRD kinetics (molecular residual disease) [ Time Frame: 2-years ]
    molecular diagnostics of markers in peripheral blood / bone marrow

  7. Cumulative incidence of relapse [ Time Frame: 2-year ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Diagnosis of c-KIT mutated t(8;21) AML i.e.

    1. >20% myeloid blasts in bone marrow and/or peripheral blood at initial diagnosis
    2. Plus cytogenetic diagnosis of aberration t(8;21)/AML1-ETO
    3. Plus mutation of c-KIT gene (mut-KIT17 or mut-KIT8) or FLT3-ITD mutation or both c-KIT and FLT3-ITD mutations
  • Chemoresponsive disease as determined by early bone marrow assessment on day 14-16 after first cycle of induction therapy with cytarabine in combination with daunorubicine or idarubicine, or mitoxantrone- Fit for further intensive chemotherapy
  • Age 18-65 years
  • ECOG performance status of 0-2
  • Life expectancy of at least 12 weeks

Exclusion Criteria:

  • Primary refractory or previously relapsed AML
  • Non-eligibility for high-dose cytarabine based consolidation, e.g. intolerance to cytarabine
  • Inability to swallow oral medications
  • Symptomatic congestive heart failure
  • Bilirubin >2.5 x upper limit of normal

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01830361

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Klinikum Chemnitz gGmbH, Klinik für Innere Medizin III
Chemnitz, Germany
Universitätsklinikum Dresden Medizinische Klinik und Poliklinik I
Dresden, Germany
Universitätsklinikum Erlangen, Medizinische Klinik 5
Erlangen, Germany
Klinikum der Johann-Wolfgang-Goethe Universität
Frankfurt Main, Germany
Universitätsklinikum Heidelberg
Heidelberg, Germany
Universitätsklinikum Jena, Klinik für Innere Medizin II
Jena, Germany
Universitätsklinikum Gießen und Marburg GmbH
Marburg, Germany
Universitätsklinikum Münster
Münster, Germany
Städtisches Klinikum Nord
Nürnberg, Germany
Klinikum der Universität Regensburg
Regensburg, Germany
Sponsors and Collaborators
Technische Universität Dresden
Novartis Pharmaceuticals
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Principal Investigator: Christoph Röllig, Prof. Dr. Medizinische Fakultät der TU Dresden, Medizinische Klinik und Poliklinik I
Additional Information:
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Responsible Party: Technische Universität Dresden Identifier: NCT01830361    
Other Study ID Numbers: TUD-MIDOKI-052
2011-002567-17 ( EudraCT Number )
First Posted: April 12, 2013    Key Record Dates
Last Update Posted: August 6, 2020
Last Verified: August 2020
Keywords provided by Technische Universität Dresden:
Acute Myeloid Leukemia
Additional relevant MeSH terms:
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Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action