A randomized phase II multicenter study to assess the tolerability and efficacy of the addition of midostaurin to 10-day decitabine in UNFIT (i.e. HCT-CI >= 3) adult AML and high risk myelodysplasia (MDS) (IPSS-R > 4.5) patients. A study in the frame of the masterprotocol of parallel randomized phase II studies in UNFIT- AML/high-risk MDS patients.

A randomized phase II multicenter study to assess the tolerability and efficacy of the addition of midostaurin to 10-day decitabine in UNFIT (i.e. HCT-CI >= 3) adult AML and high risk myelodysplasia (MDS) (IPSS-R > 4.5) patients. A study in the frame of the masterprotocol of parallel randomized phase II studies in UNFIT- AML/high-risk MDS patients. - HOVON 155 AML

Status

Recruiting

Phases

Phase 2

Study type

Interventional

Source

NL-OMON

Registry ID

NL-OMON55438

Enrollment

Registered

2019-01-31

Start date

2020-01-02

Completion date

Unknown

Last updated

2024-11-11

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Acute myeloid leukemia myelodysplastic syndromes

Interventions

Patients in this study are treated with 10-day decitabine treatment with or without midostaurin. The starting dose of midostaurin will be 50 mg bid (twice daily). During the part A run-in phase the

Eligibility

Age

18 Years to 99 Years

Inclusion criteria

Inclusion criteria: • 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 IPSS-R > 4.5 • Patients 18 years and older. • Patients NOT eligible for standard chemotherapy, defined as HCT-CI >= 3. (Appendix G) or Patients NOT eligible for standard chemotherapy for other reasons (wish of patient). • WBC

Exclusion criteria

Exclusion criteria: • 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 • 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 (

Design outcomes

Primary

Measure	Time frame
• Cumulative CR/CRi rate during 3 cycles	—

Secondary

Measure	Time frame
Secundary endpouints: • Safety and tolerability of midostaurin added to 10-day decitabine treatment for AML (type, frequency, severity and relationship of adverse events to study treatment). • Efficacy profile (response rate after each first three cycles and best response during three cycles and after 9 months (CRMRD-, CR, CRi, MLFS, PR)) • Event free survival (EFS) • Overall survival (OS)). • Days of staying in hospital and transfusion needs during three cycles. • Prognostic value of MRD (by flowcytometry or PCR). • Gene mutations predictive of response, EFS and OS by exploratory analysis. • Prognostic value of baseline physical and functional conditions using comprehensive geriatric assessment tools (short physical performance battery (SPPB) and activities of daily living (ADL) on treatment outcome. Translational endpoints To identify potential biomarkers (molecular) that predict for response to decitabine and/or midostaurin.	—

Measure

Time frame

Secundary endpouints: • Safety and tolerability of midostaurin added to 10-day decitabine treatment for AML (type, frequency, severity and relationship of adverse events to study treatment). • Efficacy profile (response rate after each first three cycles and best response during three cycles and after 9 months (CRMRD-, CR, CRi, MLFS, PR)) • Event free survival (EFS) • Overall survival (OS)). • Days of staying in hospital and transfusion needs during three cycles. • Prognostic value of MRD (by flowcytometry or PCR). • Gene mutations predictive of response, EFS and OS by exploratory analysis. • Prognostic value of baseline physical and functional conditions using comprehensive geriatric assessment tools (short physical performance battery (SPPB) and activities of daily living (ADL) on treatment outcome. Translational endpoints To identify potential biomarkers (molecular) that predict for response to decitabine and/or midostaurin.

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Countries

Netherlands

Outcome results

None listed

Source: NL-OMON (via WHO ICTRP)