NCT04687098

Risk-adapted Therapy for Primary Acute Myeloid Leukemia

Risk-adapted Therapy for Primary Acute Myeloid Leukemia (AML) in Adult Patients up to 70 Years Old

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 1,034 (actual)
• Sponsor: Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias · Academic / Other
• Sex: All
• Age: 17 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

The AML-12 study investigates the efficacy and toxicity of standard induction chemotherapy with idarubicin and cytarabine (IC) with G-CSF priming followed by a risk-adapted post remission therapy for patients up to the age of 70 diagnosed with de novo acute myeloid leukemia (AML). Modifications from the previous protocol AML-03 (NCT01723657) include removal of etoposide in induction, limitation of the GCSF priming to the induction phase and categorization of post remission therapy (stem cell transplant or 2 high dose cytarabine consolidations) according to diagnostic genetics as well as post-remission clearance of measurable residual disease. The aims of these modifications are to improve the overall survival and leukemia free survival of acute myeloid leukemia patients with a risk-adapted approach.

Detailed description

Induction chemotherapy: Idarubicin (12mg/m2/day intravenous, days 1-3), Low-dose cytarabine (200mg/m2/day, intravenous in continuous infusion, days 1-7) and G-CSF priming 150mcg/m2/day, subcutaneous from day 0 to the last day of chemotherapy if white blood cell count (WBC) \<30x10E9/L. This induction chemotherapy can be repeated twice in the case of partial response (PR) to achieve complete response (CR). Once CR is achieved (with one or two induction cycles), all patients receive a consolidation course with high-dose cytarabine (3000mg/m2/12h days 1, 3 and 5) and pegfilgrastim 6mg on day 6. After this, patients will be allocated to the different risk groups as follows: * Favorable risk group \[patients with t(8;21)(q22;q22)/RUNX1/RUNX1T1, inv(16)(p12;q22) or t(16;16)/CBFB/MYH11; Intermediate risk cytogenetics (MRC 2010) and NPM1 mutation with FLT3 wild type or low ratio of FLT3 internal tandem duplication (ITD)/wild type (\<0.5); or CEBPA biallelic mutation\]. Patients in this group will receive 2 additional courses of consolidation therapy * Intermediate risk group \[Intermediate risk cytogenetics (MRC 2010) without NPM1 mutations, FLT3-ITD, or CEBPA biallelic mutation\]. Patients in this group receive an allogeneic stem cell transplant in first CR. Patients without an available donor can be autografted per center decision * Adverse risk group \[Adverse risk cytogenetics (MRC 2010), intermediate cytogenetics with FLT3-ITD without NPM1 mutation or NPM1-FLT3-ITD high ratio or MLL rearrangement; any favorable or intermediate risk patients with positive MRD following 1 (intermediate) or 2 (favorable) consolidation courses\]. Intention to treat of those patients is allogeneic stem cell transplant from any source.

Conditions

• Leukemia, Myeloid, Acute

Interventions

Type	Name	Description
DRUG	Idarubicin	12 mg/m2/day; intravenous, administration at induction phase, days 1 to 3.
DRUG	Ara-C	200mg/m2/day, intravenous at induction phase; days 1-7. \- High dose during consolidation phase. In patients up to 60 years 3g/m2/12hours days 1,3,5, and patients 60 to 70 years: 1.5g/m2/12hours days 1,3,5.
DRUG	G-CSF	* Administration at induction phase to remission days 1 to 7. G-CSF will not be initiated if the leukocyte count is over 30x10e9/L at diagnosis or will be interrupted if the leukocyte count during treatment arises 30x10e9/L. * Administration at consolidation phase day 7.
PROCEDURE	Allogeneic matched or unrelated donor transplant.	To be performed in patients in the intermediate or adverse risk groups.
PROCEDURE	Autologous peripheral blood stem cell transplant	To be considered in patients in the intermediate risk group without an available allogeneic donor and negative measurable residual disease, per center decision.
PROCEDURE	Measurable residual disease	To be performed either with molecular monitoring or, if not applicable, by flow cytometry. Pre-stablished cut-off values are defined for decision-making.

Timeline

• Start date: 2012-02-01
• Primary completion: 2022-07-31
• Completion: 2022-11-10
• First posted: 2020-12-29
• Last updated: 2023-06-27

Locations

15 sites across 1 country: Spain