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Acute Myeloid LeukemiaPhase 2MIDOKITNCT01830361

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

A Phase 2 study testing midostaurin (PKC412) in people with Acute Myeloid Leukemia, run by Technische Universität Dresden at 10 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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 Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Acute Myeloid Leukemia
What is being tested?
midostaurin (PKC412)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
10 sitesGermany
Study dates
13 Mar 2013to 30 Oct 2019
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Diagnosis of c-KIT mutated t(8;21) AML i.e.
  • >20% myeloid blasts in bone marrow and/or peripheral blood at initial diagnosis
  • Plus cytogenetic diagnosis of aberration t(8;21)/AML1-ETO
  • 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

Who cannot join

  • 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

Trial locations and contacts

10 sites in 1 country.

10 sites in 1 country

Germany10 sites

  • Klinikum Chemnitz gGmbH, Klinik für Innere Medizin III

    Chemnitz

  • Universitätsklinikum Dresden Medizinische Klinik und Poliklinik I

    Dresden

  • Universitätsklinikum Erlangen, Medizinische Klinik 5

    Erlangen

  • Klinikum der Johann-Wolfgang-Goethe Universität

    Frankfurt am Main

  • Universitätsklinikum Heidelberg

    Heidelberg

  • Universitätsklinikum Jena, Klinik für Innere Medizin II

    Jena

  • Universitätsklinikum Gießen und Marburg GmbH

    Marburg

  • Universitätsklinikum Münster

    Münster

  • Städtisches Klinikum Nord

    Nuremberg

  • Klinikum der Universität Regensburg

    Regensburg

Other trials in Germany

About this study

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

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

Read the 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.

Being tested
midostaurin (PKC412)
Keywords
AML, Acute Myeloid Leukemia, c-KIT, FLT3-ITD, t(8;21), chemotherapy, midostaurin
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • midostaurin (PKC412)Drug

    Also called Rydapt

    Midostaurin 50 mg (2 capsules) twice daily days 8-21 in induction II + consolidation I-III; maintenance treatment twice daily continuously for 12 months

Study groups in NCT01830361
Study groupRoleWhat they receive
midostaurin (PKC412), capsulesExperimentalmidostaurin 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.
Receives: Drug: midostaurin (PKC412)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Event-free Survival

    Measured: 2-year Event-free Survival

Secondary outcomes (7)

  1. Time to relapse

    Measured: 2-years

  2. Overall survival

    Measured: 2-years

  3. Relapse-free survival

    Measured: 2-years

  4. morphologic and molecular CR rate

    Measured: 2-years

  5. incidence of AEs/SAEs

    Measured: until 30 days after end of treatment

  6. MRD kinetics (molecular residual disease)

    molecular diagnostics of markers in peripheral blood / bone marrow

    Measured: 2-years

  7. Cumulative incidence of relapse

    Measured: 2-year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Apr 2013 (estimated)
  2. Study start13 Mar 2013
  3. Primary completion30 Oct 2019
  4. Study completion30 Oct 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01830361
Sponsor's protocol ID
TUD-MIDOKI-052
Other IDs
2011-002567-17
Acronym
MIDOKIT
Status last verified
Aug 2020
First submitted
25 Mar 2013
Last updated
6 Aug 2020
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing midostaurin (PKC412) in people with Acute Myeloid Leukemia, run by Technische Universität Dresden at 10 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Event-free Survival (time frame: 2-year Event-free Survival). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01830361.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2020.

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