Combination of Midostaurin and Gemtuzumab Ozogamicin in First-line Standard Therapy for Acute Myeloid Leukemia (MOSAIC)

NCT04385290 | Recruiting Phase 1

• 1 other identifier: TUD-MOSAIC-075
• Study Type: interventional
• Target: 214
• Locations: 1 country
• Sites: 21

Brief Summary

This phase I/II clinical trial evaluates the safety and efficacy of the combined administration of midostaurin and gemtuzumab ozogamicin in the frame of first-line standard chemotherapy in newly diagnosed acute myeloid leukemia (AML) patients displaying a cytogenetic aberration or fusion transcript in the core-binding factor (CBF) genes or FMS-like tyrosine Kinase 3 (FLT3) mutation.

Conditions

Acute Myeloid Leukemia

Keywords

AML; FLT3 mutation; CBF; midostaurin; gemtuzumab ozogamicin

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose (MTD) of midostaurin and GO combination

  as measured by the number of dose limiting toxicities related to midostaurin or GO exposure.

  treatment day 8 until day 42 at the latest

• Event Free Survival (EFS)

  Time interval from date of randomization until either primary treatment failure or relapse or death, whichever occurs first.

  up to 3 years from enrolment

Secondary Outcomes (6)

• CR/CRi rate

  after induction treatment, approx. 2 months

• Duration of remission

  up to 3 years from enrolment

• Cumulative incidence of relapse

  up to 3 years from enrolment

• Relapse-free survival

  up to 3 years from enrolment

• Overall survival

  up to 3 years from enrolment

Study Arms (5)

MODULE trial: dose escalation

EXPERIMENTAL

Phase I (Trial part MODULE): The treatment plan combines increasing doses levels of midostaurin (25/50 mg BID) and gemtuzumab ozogamicin (3 mg/m\^2 i.v. max 4.5 mg on day(s) 1, (4, 7)) with 7+3 standard chemotherapy scheme using cytarabine (200 mg/m\^2 cont. inf. i.v. on days 1 to 7) and daunorubicin (60 mg/m\^2 i.v. on days 1 to 3).

Drug: MODULE: conventional chemotherapy (Cytarabine+Daunorubicin) in combination with midostaurin+GO

MAGNOLIA-trial: conventional chemotherapy+GO and midostaurin

EXPERIMENTAL

Phase II (Trial part MAGNOLIA): midostaurin (recommended phase II dose, RP2D) is combined with treatment standard (7+3 standard chemotherapy scheme using cytarabine 200 mg/m\^2 cont. inf. i.v. and daunorubicin 60 mg/m\^2 i.v.) plus GO (recommended phase II dose, RP2D) in CBF AML

Drug: MAGNOLIA-trial: Midostaurin associated with conventional chemotherapy (AraC+DNR)+GO

MAGNOLIA-trial: conventional chemotherapy+GO

ACTIVE COMPARATOR

Phase II (Trial part MAGNOLIA): treatment standard of CBF AML (7+3 standard chemotherapy scheme using cytarabine 200 mg/m\^2 cont. inf. i.v. and daunorubicin 60 mg/m\^2 i.v. plus GO (3 mg/m\^2 i.v. max 4.5 mg) on days 1, 4, 7). No additional Midostaurin is given.

Drug: MAGNOLIA-trial: conventional chemotherapy (AraC+DNR)+GO

MAGMA-trial: conventional chemotherapy+midostaurin and GO

EXPERIMENTAL

Phase II (Trial part MAGMA): GO (recommended phase II dose, RP2D) is combined with treatment standard (7+3 standard chemotherapy scheme using cytarabine 200 mg/m\^2 cont. inf. i.v. and daunorubicin 60 mg/m\^2 i.v.) plus Midostaurin (recommended phase II dose, RP2D) in FLT3 mutated AML

Drug: MAGMA-trial:GO associated with conventional chemotherapy (AraC+DNR)+Midostaurin

MAGMA-trial: conventional chemotherapy+midostaurin

ACTIVE COMPARATOR

Phase II Trial (MAGMA): treatment standard of FLT3 mutated AML (7+3 standard chemotherapy scheme using cytarabine 200 mg/m\^2 cont. inf. i.v. and daunorubicin 60 mg/m\^2 i.v plus midostaurin). No additional GO is given.

Drug: MAGMA-trial: conventional chemotherapy (AraC+DNR)+Midostaurin

Interventions

MODULE: conventional chemotherapy (Cytarabine+Daunorubicin) in combination with midostaurin+GO DRUG

Midostaurin (IMP) induction: 25 mg or 50 mg peroral BID, days 8 to 21 depending on assigned dose level GO (IMP) induction: 3 mg/m\^2 i.v. max 4.5 mg, on day1, or on days 1, 4, or days 1, 4, 7 depending on assigned dose level Daunorubicin (DNR, non-IMP) induction: 60 mg/m\^2/day i.v., days 1 to 3 Cytarabine (AraC, non-IMP) induction: 200 mg/m\^2/day cont. infusion, days 1 to 7

Also known as: Rydapt, Mylotarg

MODULE trial: dose escalation

MAGNOLIA-trial: Midostaurin associated with conventional chemotherapy (AraC+DNR)+GO DRUG

Midostaurin (IMP): RP2D peroral, days 8 to 21, induction cycle 1; 50 mg peroral BID, days 8 to 21 induction cycle 2; 50 mg peroral BID, days 8 to 21, 3 consolidation cycles; 50 mg peroral BID, days 1 to 28, 12 maintenance cycles; GO (IMP): 3 mg/m\^2 i.v. max 4.5 mg, RP2D, 1 induction cycle only Daunorubicin (DNR, non-IMP): 60 mg/m\^2 i.v., days 1 to 3 of induction cycle 1 and 2 in good and moderate responders; 50 mg/m\^2/day i.v., days 1 to 3 of induction cycle 2 in non-responders Cytarabine (AraC, non-IMP): 200 mg/m\^2/day cont. infusion, days 1 to 7 of induction cycles 1 and 2 in good and moderate responders; 3000/1500 mg/m\^2/day i.v. BID, days 1 to 3 of induction cycle 2 in non-responders; 3000/1500 mg/m\^2 i.v. BID, days 1, 3, 5 of consolidation, 3 cycles

Also known as: Rydapt, Mylotarg

MAGNOLIA-trial: conventional chemotherapy+GO and midostaurin

MAGNOLIA-trial: conventional chemotherapy (AraC+DNR)+GO DRUG

GO (IMP): 3 mg/m\^2 i.v. max 4.5 mg on days 1, 4, 7; 1 induction cycle only Daunorubicin (DNR, non-IMP): 60 mg/m\^2/day i.v., days 1 to 3 of induction cycle 1 and 2 in good and moderate responders; 50 mg/m\^2/day i.v., days 1 to 3 of induction cycle 2 in non-responders Cytarabine (AraC, non-IMP): 200 mg/m\^2/day cont. infusion, days 1 to 7 of induction cycles 1 and 2 in good and moderate responders; 3000/1500 mg/m\^2/day i.v. BID, days 1 to 3 of induction cycle 2 in non-responders; 3000/1500 mg/m\^2 i.v. BID, days 1, 3, 5 of consolidation, 3 cycles

Also known as: Mylotarg

MAGNOLIA-trial: conventional chemotherapy+GO

MAGMA-trial:GO associated with conventional chemotherapy (AraC+DNR)+Midostaurin DRUG

Midostaurin (IMP): RP2D peroral, days 8 to 21, induction cycle 1; 50 mg peroral BID, days 8 to 21, induction cycle 2; 50 mg peroral BID, days 8 to 21, 3 consolidation cycles; 50 mg peroral BID, days 1 to 28, 12 maintenance cycles; GO (IMP): 3 mg/m\^2 i.v. max 4.5 mg, RP2D, 1 induction cycle only Daunorubicin (DNR, non-IMP): 60 mg/m\^2/day i.v., days 1 to 3 of induction cycles 1-2 in good and moderate responders; 50 mg/m\^2/day i.v., days 1 to 3 of induction cycle 2 in non-responders Cytarabine (AraC, non-IMP): 200 mg/m\^2/day cont. infusion, days 1 to 7 of induction cycles 1 and 2 in good and moderate responders; 3000/1500 mg/m\^2/day i.v. BID, days 1 to 3 of induction cycle 2 in non-responders; 3000/1500 mg/m\^2 i.v. BID, days 1, 3, 5 of consolidation, 3 cycles

Also known as: Mylotarg, Rydapt

MAGMA-trial: conventional chemotherapy+midostaurin and GO

MAGMA-trial: conventional chemotherapy (AraC+DNR)+Midostaurin DRUG

Midostaurin (IMP): RP2D peroral, days 8 to 21, induction cycle 1; 50 mg peroral BID, days 8 to 21 induction cycle 2; 50 mg peroral BID, days 8 to 21, 3 consolidation cycles; 50 mg peroral BID, days 1 to 28, 12 maintenance cycles Daunorubicin (DNR, non-IMP): 60 mg/m\^2/day i.v., days 1 to 3 of induction cycle 1 and 2 in good and moderate responders; 50 mg/m\^2/day i.v., days 1 to 3 of induction cycle 2 in non-responders Cytarabine (AraC, non-IMP): 200 mg/m\^2/day cont. infusion, days 1 to 7 of induction cycles 1 and 2 in good and moderate responders; 3000/1500 mg/m\^2/day i.v. BID, days 1 to 3 of induction cycle 2 in non-responders; 3000/1500 mg/m\^2 i.v. BID, days 1, 3, 5 of consolidation, 3 cycles

Also known as: Rydapt

MAGMA-trial: conventional chemotherapy+midostaurin

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent
• Newly diagnosed AML according to the criteria of the World Health Organisation plus the following molecular or cytogenetic specifications:
• Phase I Trial - MODULE:
• t(8;21)/RUNX1-RUNX1T1 or
• inv(16) or t(16;16)/CBFB-MYH11 or
• FLT3-ITD or
• FLT3-tyrosine kinase domain (FLT3-TKD)
• Phase II Trial - MAGNOLIA
• t(8;21)/RUNX1-RUNX1T1 or
• inv(16) or t(16;16)/CBFB-MYH11
• Phase II Trial - MAGMA
• FLT3-ITD or
• FLT3-TKD
• Absence of mutations in CBF genes (i.e. t(8;21)/RUNX1-RUNX1T1 or inv(16) or t(16;16)/CBFB-MYH11)
• Male and female patients aged

You may not qualify if:

• 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
• central nervous system involvement
• Isolated extramedullary AML
• Uncontrolled infection
• AML after antecedent myelodysplasia (MDS) with prior cytotoxic treatment (e.g., azacytidine or decitabine)
• Any investigational agent within 30 days or 5 half-lives, whichever is greater, prior to day 1. An investigational agent is defined as an agent with no approved medical use in adults or in pediatric patients
• Prior treatment with a FLT3 inhibitor (e.g., midostaurin, quizartinib, sorafenib)
• Strong CYP3A4/5 enzyme inducing drugs unless they can be discontinued or replaced prior to enrollment
• Any other known disease or concurrent severe and/or uncontrolled medical condition (e.g., cardiovascular disease including congestive heart failure or active uncontrolled infection) that could compromise participation in the study
• Impairment of gastrointestinal (GI) function or GI disease that might alter significantly the absorption of midostaurin
• Confirmed diagnosis of HIV infection,
• Active viral hepatitis unless serology demonstrates clearance of infection. Occult or prior hepatitis B virus (HBV) infection, defined as negative hepatitis B surface antigen and positive total hepatitis core antibodies, may be included if HBV DNA is undetectable, provided that patients are willing to undergo monthly DNA testing. Patients who have protective titers of hepatitis B surface antibody after vaccination or prior cured hepatitis B are eligible. Patients for hepatitis C virus (HCV) antibody are eligible provided PCR is negative for HCV RNA.
• Cardiovascular abnormalities, including any of the following:
• History of myocardial infarction, angina pectoris, Coronary Artery Bypass Grafting within 6 months prior to starting study treatment

Sponsors & Collaborators

• Technische Universität Dresden: lead
• Novartis Pharmaceuticals: collaborator
• Pfizer: collaborator

Study Sites (21)

LMU Klinikum, Campus Großhadern

München, Bavaria, 81377, Germany

RECRUITING

Universitätsklinikum Essen

Essen, North Rhine-Westphalia, 45147, Germany

RECRUITING

Universitätsklinikum Aachen

Aachen, 52074, Germany

RECRUITING

Universitätsklinikum Augsburg

Augsburg, 86156, Germany

NOT YET RECRUITING

Klinikum Chemnitz gGmbH

Chemnitz, 09116, Germany

RECRUITING

Universitätsklinikum Dresden

Dresden, 01307, Germany

RECRUITING

Johann Wolfgang Goethe-Universität

Frankfurt am Main, 60590, Germany

RECRUITING

Universitätsklinikum Halle

Halle, 06120, Germany

RECRUITING

Universitätsklinikum Heidelberg

Heidelberg, 69120, Germany

RECRUITING

Universitätsklinikum Jena

Jena, 07740, Germany

RECRUITING

Universitätsklinikum Schleswig-Holstein

Kiel, 24105, Germany

RECRUITING

Gemeinschaftsklinikum Mittelrhein gGmbH

Koblenz, 56068, Germany

RECRUITING

Universitätsklinikum Leipzig

Leipzig, 04103, Germany

RECRUITING

Klinikum Mannheim gGmbH

Mannheim, 68167, Germany

RECRUITING

Philipps-Universität Marburg Fachbereich Medizin

Marburg, 35043, Germany

RECRUITING

Rotkreuzklinikum München gGmbH

München, 80634, Germany

RECRUITING

Universitätsklinikum Münster

Münster, 48149, Germany

RECRUITING

Klinikum Nürnberg-Nord

Nuremberg, 90419, Germany

NOT YET RECRUITING

Krankenhaus Barmherzige Brüder

Regensburg, 93049, Germany

RECRUITING

Robert-Bosch-Krankenhaus

Stuttgart, 70376, Germany

RECRUITING

Rems-Murr-Klinikum Winnenden

Winnenden, 71364, Germany

RECRUITING

Related Links

• homepage of study group

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

midostaurin; Gemtuzumab

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Calicheamicins; Aminoglycosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Christoph Röllig, Prof. Dr.

  Technische Universität Dresden, Medical Faculty Carl Gustav Carus

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Christoph Röllig, Prof. Dr.

CONTACT

+49 351 458; MOSAIC@ukdd.de

Manja Reimann, Dr.

CONTACT

+49 351 458; MOSAIC@ukdd.de

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The subtrials are not blinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The phase I dose escalation trial (MODULE) will be conducted according to the 3+3 design. The phase II trial in CBF AML (MAGNOLIA) will be conducted in a open label and randomized manner. The phase II trial in FLT3 mutated AML (MAGMA) will be conducted in a open label and randomized manner.

Study Record Dates

• First Submitted: May 8, 2020
• First Posted: May 12, 2020
• Study Start: September 4, 2020
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2028
• Last Updated: September 8, 2025

Record last verified: 2025-09

Locations

DE (21)