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

Phase 1

• 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: 21.0Level: LLTClassification code 10000886Term: Acute myeloid leukemiaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2019-003863-23-DE
• Lead Sponsor: Technische Universität Dresden

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2019-11-28
• Last Update Posted: 18 June 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 214

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 < 2 x ULN
•Creatinin < 1.5 x ULN or Creatinine clearance > 40 ml/min,
- White blood cell count < 30 × 10^9/L. Note: Hydroxyurea and/or a dose of 100-200 mg/m^2 cytarabine per day for up to 3 days (for emergency use
for clinical stabilization) is permitted to meet this criterion.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 214
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 214

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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified