Clinical trial NCT04687098: Risk-adapted Therapy for Primary Acute Myeloid Leukemia
Official title: Risk-adapted Therapy for Primary Acute Myeloid Leukemia (AML) in Adult Patients up to 70 Years Old
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia, Myeloid, Acute
Keywords: Leukemia
Myeloid
Lead sponsor: Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias
Sponsor class: OTHER
First posted: 2020-12-29
Enrollment: 1034
Sex: ALL
Minimum age (years): 17
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: Inclusion Criteria:

* Patients with newly diagnosed AML, classified using the World Health Organization (WHO) 2017 criteria.
* Patients with 70 years old or younger.

Exclusion Criteria:

* Patients previously treated for the AML with chemotherapy different from hydroxyurea.
* Acute promyelocytic leukemia with t(15;17).
* Chronic myeloid leukemia in blastic phase.
* Secondary AML or therapy related AML.
* Presence of concomitant active neoplastic disease.
* Abnormal renal and hepatic functions with creatinin and/or bilirubin 2 times higher than the normal threshold, except when the alteration should be attributed to the leukemia.
* Patients with a cardiac ejection fraction below 45%, symptomatic cardiac deficiency or both.
* Patients with neurological or concomitant psychiatric disease.
* HIV infection.

Primary outcomes:
measure: Complete remission rate (CRR)
timeFrame: 2 months
measure: Disease free survival (DFS)
timeFrame: 4 years
measure: Relapse rate (RR)
timeFrame: 4 years
Secondary outcomes:
measure: Feasibility of treatment completion
timeFrame: 4 years
measure: Survival outcome analysis of the 3 risk-adapted categories (favourable, intermediate and adverse)
timeFrame: 4 years
measure: Feasibility of centralized monitoring of measurable residual disease (MRD)
timeFrame: 4 years
measure: Comparison of global outcomes with previous protocol (AML-03) and other published protocols.
timeFrame: 4 years
Other outcomes:
Locations:
city: Badalona
country: Spain
facility: ICO Badalona-Hospital Universitari Germans Trias i Pujol
state: Barcelona
city: Hospitalet de Llobregat
country: Spain
facility: ICO Hospital Universitari de Bellvitge
state: Barcelona
city: Palma de Mallorca
country: Spain
facility: Hospital Universitari Son Espases
state: Mallorca
city: Palma de Mallorca
country: Spain
facility: Hospital Universitari Son Llatzer
state: Mallorca
city: Tortosa
country: Spain
facility: Hospital Verge de la Cinta
state: Tarragona
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic Barcelona
city: Girona
country: Spain
facility: ICO-Girona Hopital Universitari de Girona Dr. Josep Trueta
city: Lleida
country: Spain
facility: Hospital Universitari Arnau de Vilanova
city: Malaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria
city: Tarragona
country: Spain
facility: ICO Tarragona-Hospital Universitari Joan XXIII
city: Terrassa
country: Spain
facility: Mutua de Terrassa
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
Study officials:
affiliation: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
name: Jorge Sierra, Prof, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Clinic of Barcelona
name: Jordi Esteve, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: