Addition of midostaurin and gemtuzumab ozogamicin to standard chemotherapy with cytarabine and daunorubicin in patients with newly diagnosed acute myeloid leukemia

Midostaurin + Gemtuzumab Ozogamicin combination in first-line standard therapy for acute myeloid leukemia - MOSAIC

Status

Active, not recruiting

Phases

Phase 1Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2019-003863-23-DE

Enrollment

214

Registered

2019-11-28

Start date

2020-07-03

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

Patients with newly diagnosed acute myeloid leukemia (AML) fit for intensive curative treatment displaying a cytogenetic aberration or fusion transcript in the core-binding factor (CBF) genes or FLT3 mutation MedDRA version: 21.0 Level: LLT Classification code 10000886 Term: Acute myeloid leukemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Interventions

Trade Name: Rydapt Product Name: Rydapt Pharmaceutical Form: Capsule, soft INN or Proposed INN: MIDOSTAURIN CAS Number: 120685-11-2 Other descriptive name: MIDOSTAURIN Concentration unit: mg milligram

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: - Written informed consent - Newly diagnosed AML according to WHO criteria plus the following molecular or cytogenetic specifications: o Phase I (Dose escalation): • t(8;21)/RUNX1-RUNX1T1 or • inv(16) or t(16;16)/CBFB-MYH11 or • FLT3-ITD or • FLT3-TKD o Phase II (MAGNOLIA) Expansion in CBF AML • t(8;21)/RUNX1-RUNX1T1 or • inv(16) or t(16;16)/CBFB-MYH11, o Phase II (MAGMA) Expansion in FLT3mut AML • FLT3-ITD or • FLT3-TKD • Absence of mutations in the core-binding factor genes (i.e. t(8;21)/RUNX1-RUNX1T1 or inv(16) or t(16;16)/CBFB-MYH11) - Male and female patients with age • 18-70 years - ECOG 0-2, - Life expectancy > 14 days, - Adequate hepatic and renal function • ALAT/ASAT = 2.5 x ULN • Bilirubin 40 ml/min, - White blood cell count =65 years) yes F.1.3.1 Number of subjects for this age range 214

Exclusion criteria

Exclusion criteria: - Previous antineoplastic treatment for AML other than hydroxyurea and/or cytarabine for emergency use (100-200 mg/m^2 per day on maximal 3 days), - Previous treatment with anthracyclines, - CNS involvement, - Uncontrolled infection, - Strong CYP3A4/5 enzyme inducing drugs unless they can be discontinued or replaced prior to enrollment.

Design outcomes

Primary

Measure	Time frame
Main Objective: To evaluate the tolerability and efficacy of midostaurin plus gemtuzumab ozogamicin (GO) in combination with standard AML induction chemotherapy ;Secondary Objective: To investigate potential correlations between CD33 expression, c-kit expression, FLT3-ITD mutational load and response;Primary end point(s): - Phase I (Dose escalation): Maximum tolerated dose of midostaurin plus gemtuzumab ozogamicin in combination with standard induction chemotherapy within a 3+3 design - Phase II (Expansion): Event-free survival;Timepoint(s) of evaluation of this end point: Phase I: day 28-42 of induction cycle 1 = DLT Evaluation period Phase II: up to 3 years from enrolment (unless the event occurs earlier)	—

Measure

Time frame

Main Objective: To evaluate the tolerability and efficacy of midostaurin plus gemtuzumab ozogamicin (GO) in combination with standard AML induction chemotherapy ;Secondary Objective: To investigate potential correlations between CD33 expression, c-kit expression, FLT3-ITD mutational load and response;Primary end point(s): - Phase I (Dose escalation): Maximum tolerated dose of midostaurin plus gemtuzumab ozogamicin in combination with standard induction chemotherapy within a 3+3 design - Phase II (Expansion): Event-free survival;Timepoint(s) of evaluation of this end point: Phase I: day 28-42 of induction cycle 1 = DLT Evaluation period Phase II: up to 3 years from enrolment (unless the event occurs earlier)

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Secondary

Measure	Time frame
Secondary end point(s): - CR/CRi rate, - Depth of remission and measurable residual disease (MRD) by PCR-based RUNX1-RUNX1T1 or CBFB-MYH11 and NPM1 measurements and by multicolor flow cytometry (MFC), - Duration of remission, cumulative incidence of relapse, - Relapse-free survival, - Overall survival, - Early mortality (ED30, ED60), - Tolerability (toxicity, adverse events, VOD), - CD33 expression of AML blasts, - Proportion of allogeneic stem cell transplantation following response. ;Timepoint(s) of evaluation of this end point: up to 3 years from enrolment	—

Measure

Time frame

Secondary end point(s): - CR/CRi rate, - Depth of remission and measurable residual disease (MRD) by PCR-based RUNX1-RUNX1T1 or CBFB-MYH11 and NPM1 measurements and by multicolor flow cytometry (MFC), - Duration of remission, cumulative incidence of relapse, - Relapse-free survival, - Overall survival, - Early mortality (ED30, ED60), - Tolerability (toxicity, adverse events, VOD), - CD33 expression of AML blasts, - Proportion of allogeneic stem cell transplantation following response. ;Timepoint(s) of evaluation of this end point: up to 3 years from enrolment

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Countries

Germany

Contacts

Public ContactCoordinating Investigator

Medizinische Fakultät Carl Gustav Carus der TU Dresden, Medizinische Klinik und Poliklinik I

MOSAIC@ukdd.de00493514583775

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026