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AML/MDSPhase 2HO155NCT04097470

Tolerability and Efficacy of Midostaurin to 10-day Decitabine in Unfit Adult AML and High Risk MDS Patients

A Phase 2 study testing Decitabine and Midostaurin in people with AML/MDS, run by Stichting Hemato-Oncologie voor Volwassenen Nederland at 37 sites in 4 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

The aim of this study is to investigate how safe and effective the addition of the new medicine midostaurin to decitabine is for the treatment of unfit acute myeloid leukemia (AML) and high-risk myelodysplasia (MDS) patients. Read more about this study

Who is it for?
Ages 18 to 100 years
Conditions the study is for
AML/MDS
What is being tested?
Decitabine and Midostaurin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
140 participants
Where
37 sitesin 4 countries
Study dates
5 Dec 2019to Nov 2026
Phase
Phase 2
Are there results?
Not yet: the study is under way

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 100 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients with:
  • a diagnosis of AML and related precursor neoplasms according to WHO 2016 classification (excluding acute promyelocytic leukemia) including secondary AML (after an antecedent hematological disease (e.g. MDS) and therapy-related AML, or
  • a diagnosis of myelodysplastic syndrome with excess of blasts (MDS) and International Prognostic Score System (IPSS) > 4.5
  • Patients 18 years and older.
  • Patients NOT eligible for standard chemotherapy, defined as hematopoietic cell transplantation comorbidity index (HCT-CI) ≥ 3.
  • or Patients NOT eligible for standard chemotherapy for other reasons (wish of patient).
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  • White blood cell (WBC) ≤ 30 x109/L (prior hydroxyurea allowed for a maximum of 5 days, stop 2 days before start decitabine treatment)
  • Adequate renal and hepatic functions unless clearly disease related as indicated by the following laboratory values:
  • Serum creatinine ≤ 221.7 µmol/L (≤ 2.5 mg/dL ), unless considered AML-related
  • Serum bilirubin ≤ 2.5 x upper limit of normal (ULN), unless considered AML-related or due to Gilbert's syndrome
  • Alanine transaminase (ALT) ≤ 2.5 x ULN, unless considered AML-related
  • WHO performance status 0, 1 or 2.
  • Patient is willing and able to use adequate contraception during and until 5 months after the last protocol treatment.
  • Written informed consent.
  • Patient is capable of giving informed consent.

Who cannot join

  • Acute promyelocytic leukemia.
  • Acute leukemia's of ambiguous lineage according to WHO 2016
  • Patient has symptomatic central nervous system (CNS) leukemia (NO routinely lumbar puncture required to investigate CNS involvement)
  • Blast crisis of chronic myeloid leukemia.
  • Diagnosis of any previous or concomitant malignancy is an exclusion criterion:
  • except when the patient completed successfully treatment (chemotherapy and/or surgery and/or radiotherapy) with curative intent for this malignancy at least 6 months prior to randomization. OR
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  • except for basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix
  • Patients previously treated for AML (any antileukemic therapy including investigational agents), a short treatment period ( ≤ 5 days) with Hydroxyurea is allowed
  • Current concomitant chemotherapy, radiation therapy, or immunotherapy; other than hydroxyurea
  • Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, infection, hypertension, pulmonary disease etc.)
  • Cardiac dysfunction as defined by:
  • Myocardial infarction within the last 3 months of study entry, or
  • Reduced left ventricular function with an ejection fraction < 40% as measured by MUGA scan or echocardiogram or
  • Unstable angina or
  • New York Heart Association grade IV congestive heart failure or
  • Unstable cardiac arrhythmias.
  • History of stroke or intracranial hemorrhage within 6 months prior to randomization.
  • Patient has a history of human immunodeficiency virus or active infection with Hepatitis C or B.
  • Patients known to be pregnant
  • Patients with a history of non-compliance to medical regimens or who are considered unreliable with respect to compliance.
  • Patients with any serious concomitant medical condition which could, in the opinion of the investigator, compromise participation in the study.
  • Patients who have senile dementia, mental impairment or any other psychiatric disorder that prohibits the patient from understanding and giving informed consent.
  • Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule

Trial locations and contacts

37 sites in 4 countries.

37 sites in 4 countries

Netherlands23 sites

  • NL-Den Bosch-JBZ

    's-Hertogenbosch

  • NL-Amersfoort-MEANDERMC

    Amersfoort

  • NL-Amsterdam-OLVG

    Amsterdam

  • NL-Amsterdam-VUMC

    Amsterdam

  • NL-Arnhem-RIJNSTATE

    Arnhem

  • NL-Breda-AMPHIA

    Breda

  • NL-Delft-RDGG

    Delft

  • NL-Doetinchem-SLINGELAND

    Doetinchem

  • NL-Dordrecht-ASZ

    Dordrecht

  • NL-Ede-ZGV

    Ede

  • NL-Eindhoven-CATHARINA

    Eindhoven

  • NL-Eindhoven-MAXIMAMC

    Eindhoven

  • NL-Enschede-MST

    Enschede

  • NL-Groningen-UMCG

    Groningen

  • NL-Leeuwarden-MCL

    Leeuwarden

  • NL-Maastricht-MUMC

    Maastricht

  • NL-Nieuwegein-ANTONIUS

    Nieuwegein

  • NL-Nijmegen-CWZ

    Nijmegen

  • NL-Nijmegen-RADBOUDUMC

    Nijmegen

  • NL-Rotterdam-ERASMUSMC

    Rotterdam

  • NL-Den Haag-HAGA

    The Hague

  • NL-Utrecht-UMCUTRECHT

    Utrecht

  • NL-Zwolle-ISALA

    Zwolle

Other trials in Netherlands

Switzerland10 sites

  • CH-Aarau-KSA

    Aarau

  • CH-Basel-USB

    Basel

  • CH-Bellinzona-IOSI

    Bellinzona

  • CH-Bern-INSEL

    Bern

  • CH-Fribourg-HFR

    Fribourg

  • CH-Geneve (14)-HCUGE

    Geneva

  • CH-Lausanne-CHUV

    Lausanne

  • CH-Luzern-LUKS

    Lucerne

  • CH-St. Gallen-KSSG

    Sankt Gallen

  • CH-Zürich-USZ

    Zurich

Other trials in Switzerland

Belgium3 sites

  • BE-Antwerpen-ZNASTUIVENBERG

    Antwerp

  • BE-Haine-Saint-Paul-JOLIMONT

    Haine-Saint-Paul

  • BE-Roeselare-AZDELTA

    Roeselare

Other trials in Belgium

Germany1 site

  • DE-Magdeburg-OVGU

    Magdeburg

Other trials in Germany

About this study

Official title: A Randomized Phase II Multicenter Study to Assess the Tolerability and Efficacy of the Addition of Midostaurin to 10-day Decitabine Treatment in Unfit Adult Acute Myeloid Leukemia and High Risk Myelodysplasia Patients

The aim of this study is to investigate how safe and effective the addition of the new medicine midostaurin to decitabine is for the treatment of unfit acute myeloid leukemia (AML) and high-risk myelodysplasia (MDS) patients. Patients who are ineligible for intensive chemotherapy because of accompanying diseases may opt for gentler treatment. This does not produce a cure but serves to allow the quality of life to be acceptable for as long as possible. Decitabine is an example of a gentler treatment. It is effective against leukemia and has fewer side effects than intensive chemotherapy. Given in courses of 5 successive days, decitabine is registered for the treatment of AML. There is scientific research to suggest that decitabine is more effective and generally well tolerated when given in courses of 10 successive days. Therefore, treatment with 10-day courses of decitabine is the standard treatment in this scientific research. The aim is to investigate whether this standard treatment can be improved by adding a new product, midostaurin. Midostaurin is a medicine that is directed against a specific protein on leukaemia cells (FLT3).

Read the detailed description

This trial aims to develop effective treatments for unfit (i.e. Hematopoietic cell transplantation co-morbidity index (HCT-CI) ≥ 3) in adult (≥ 18 yrs) AML patients, for whom current treatment strategies are highly unsatisfactory. Therefore new treatment modalities are introduced and evaluated in multiple parallel randomized phase II studies that will be conducted within the frame of a master protocol. The scheme of this new design consists of one arm with one of the currently considered best available treatments for unfit AML patients (i.e. 10-day decitabine). After a maximum of 3 10-day courses, or less in case of good response, treatment will be continued with 5-day decitabine courses. This treatment will be compared to investigational treatments in combination with decitabine.

The competitor of the 10-day decitabine schedule will be 10-day decitabine combined (sequential) with the tyrosine kinase inhibitor midostaurin (independent of the presence of FLT3 mutations). The rationale for midostaurin is: 1) single agent midostaurin has shown efficacy in both FLT3 wild type and mutant AML; 2) it has shown efficacy in a phase III randomized controlled trial when combined with intensive chemotherapy in FLT3-mutated AML (RATIFY study); 3) midostaurin has been successfully combined with hypomethylating agents (azacitidine and decitabine) and improved the response compared with historical response rates of these drugs, suggesting at least additive affects of midostaurin with hypomethylating agents.

Conditions
AML/MDS
Being tested
Decitabine, Midostaurin

What participants receive

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

  • DecitabineDrug

    Also called Dacogen

    Decitabine dosage 20mg/m2 i.v.

  • MidostaurinDrug

    Also called Rydapt

    Midostaurin 50 mg b.i.d.

Study groups in NCT04097470
Study groupRoleWhat they receive
Arm A: DecitabineActive comparatorCycles 1-3: Decitabine 10-day; depending on day +28 bone marrow (BM) blasts after the previous cycle, next cycle consists of either 5-day (BM blasts < 5%) or 10-day (BM blasts ≥5%) decitabine. Cycles 4 and beyond: 5-day decitabine (in cycles of 4-8 weeks); continuation of these cycles until progression. Dosage for Decitabine 20 mg/m2 i.v.
Receives: Drug: Decitabine
Arm B: Decitabine and MidostaurinExperimentalCycle 1:Decitabine; 10-day schedule (start day +1) + midostaurin (start day +11). Midostaurin is given until 2 days before start next cycle of decitabine. Cycles 2-3: Decitabine 5 or 10-day schedule; depending on day +28 bone marrow blasts of the previous cycle, next cycle consist of either 5-day (BM blasts < 5%) or 10-day (BM blasts ≥5%) decitabine + midostaurin (daily, starting the day after the last dose of decitabine (i.e. day +6 or +11). Midostaurin is given until 2 days before start next cycle. Cycles 4 and beyond: 5-day decitabine (in cycles of 4-8 weeks) followed by midostaurin starting at day +6 until two days before start of next cycle of decitabine; continuation of these cycles until progression. Midostaurin is given until 2 days before start next cycle of decitabine. Dosage for Decitabine 20 mg/m2 i.v. Dosage for Midostaurin 50 mg b.i.d.
Receives: Drug: Decitabine; Drug: Midostaurin

What is being measured

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

  1. Cumulative Complete Remission (CR) / CR with incomplete blood count (CRi) rate

    Cumulative CR/CRi rate during 3 cycles

    Measured: 4-5 months

Secondary outcomes (10)

  1. Safety and tolerability of midostaurin determined by the type, frequency, severity and relationship of adverse events to study treatment

    Safety and tolerability of midostaurin added to 10-day decitabine treatment for AML (type, frequency, severity and relationship of adverse events to study treatment).

    Measured: 5 years

  2. Efficacy profile

    The response rate after first three cycles together with the best response during three cycles and after 9 months will determinine the efficacy profile.

    Measured: 4-9 months

  3. Event free survival (EFS)

    The time from registration to induction failure, death or relapse whichever occurs first).

    Measured: 5 years

  4. Overall survival (OS)

    The time from the date of randomization to the date of death, whatever the cause. Patients still alive at the date last contact will be censored.

    Measured: 5 years

  5. Hospital stay duration

    Days of staying in hospital during 3 cycles.

    Measured: 4-5 months

  6. Transfusion need

    Number of participants with transfusion needs during 3 cycles.

    Measured: 4-5 months

  7. Prognostic value of MRD

    Assessment of the prognostic value of Minimal Residual Disease (MRD) by flowcytometry or PCR

    Measured: 9 months and at relapse

  8. Predictive value of gene mutations

    Assessment of the predictive value of gene mutations by exploratory analysis

    Measured: 5 years

  9. Prognostic value of baseline physical conditions as measured by the short physical performance battery

    Assessment of the prognostic value of baseline physical and functional conditions using a comprehensive geriatric assessment tool, short physical performance battery (SPPB), on treatment outcome. Total scores (range 0 to 12) will be used to determine physical performance.

    Measured: 5 years

  10. Prognostic value of baseline functional conditions as measured by the activities of daily living

    Assessment of the prognostic value of baseline functional conditions using a comprehensive geriatric assessment tool, activities of daily living (ADL), on treatment outcome. Total points (range 0 to 6) will be used to determine functional condition.

    Measured: 5 years

Timeline

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

  1. First posted20 Sep 2019
  2. Study start5 Dec 2019
  3. Primary completion15 Nov 2021
  4. Study completionNov 2026 (estimated)

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
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
140 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04097470
Sponsor's protocol ID
HOVON 155 AML
Other IDs
2018-000047-31, 2018-674, NL64632.042.18, 2018
Acronym
HO155
Status last verified
Sep 2024
First submitted
25 Mar 2019
Last updated
19 Sep 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Decitabine and Midostaurin in people with AML/MDS, run by Stichting Hemato-Oncologie voor Volwassenen Nederland at 37 sites in 4 countries.

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 15 inclusion and 23 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: under way, not looking for participants, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 37 sites in Netherlands, Switzerland, Belgium, 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?

This study is still under way. Results are not available in the source record yet.

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?

Cumulative Complete Remission (CR) / CR with incomplete blood count (CRi) rate (time frame: 4-5 months). 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 NCT04097470.

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 19 Sep 2024.

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