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

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

Interventions

DRUG

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

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

DRUG

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

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

DRUG

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

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

DRUG

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

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

DRUG

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

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

Sponsors & Collaborators

• Novartis Pharmaceuticals

  collaborator INDUSTRY

• Pfizer

  collaborator INDUSTRY

• Technische Universität Dresden

  lead OTHER

Principal Investigators

• Christoph Röllig, Prof. Dr. · Technische Universität Dresden, Medical Faculty Carl Gustav Carus

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2020-09-04

Primary Completion

2027-04-30

Completion

2028-04-30

Countries

• Germany

Study Locations