Risk-adapted Therapy for Primary Acute Myeloid Leukemia

NCT04687098 | Completed Phase 2 DMC

• 1 other identifier: AML-12
• Study Type: interventional
• Target: 1,034
• Locations: 1 country
• Sites: 15

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.

Conditions

Leukemia, Myeloid, Acute

Keywords

Leukemia; Myeloid

Outcome Measures

Primary Outcomes (3)

• Complete remission rate (CRR)

  Analyze the efficacy and toxicity of the current doses of IC (Idarubicin and cytarabine) with G-CSF priming to achieve complete remission in patients tih AML up to 70yo.

  2 months

• Disease free survival (DFS)

  Analyze the disease free survival in the whole cohort of AML patients.

  4 years

• Relapse rate (RR)

  Analyze the relapse rate of all patients achieving remission with intensive induction followed by risk-adapted consolidation strategies.

  4 years

Secondary Outcomes (4)

• Feasibility of treatment completion

  4 years

• Survival outcome analysis of the 3 risk-adapted categories (favourable, intermediate and adverse)

  4 years

• Feasibility of centralized monitoring of measurable residual disease (MRD)

  4 years

• Comparison of global outcomes with previous protocol (AML-03) and other published protocols.

  4 years

Study Arms (1)

Risk-adapted postremission treatment.

OTHER

Induction (idarubicin, cytarabine), first consolidation (high dose cytarabine), risk- stratification: allogeneic matched related or unrelated donor transplant vs. consolidation courses.

Drug: Idarubicin; Drug: Ara-C; Drug: G-CSF; Procedure: Allogeneic matched or unrelated donor transplant.; Procedure: Autologous peripheral blood stem cell transplant; Procedure: Measurable residual disease

Interventions

Idarubicin DRUG

12 mg/m2/day; intravenous, administration at induction phase, days 1 to 3.

Also known as: Ida

Risk-adapted postremission treatment.

Ara-C DRUG

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.

Also known as: HDAC

Risk-adapted postremission treatment.

G-CSF DRUG

* 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.

Also known as: Pegfilgrastim

Risk-adapted postremission treatment.

Allogeneic matched or unrelated donor transplant. PROCEDURE

To be performed in patients in the intermediate or adverse risk groups.

Risk-adapted postremission treatment.

Autologous peripheral blood stem cell transplant PROCEDURE

To be considered in patients in the intermediate risk group without an available allogeneic donor and negative measurable residual disease, per center decision.

Risk-adapted postremission treatment.

Measurable residual disease PROCEDURE

To be performed either with molecular monitoring or, if not applicable, by flow cytometry. Pre-stablished cut-off values are defined for decision-making.

Also known as: MRD

Risk-adapted postremission treatment.

Eligibility Criteria

• Age: 17 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias: lead

Study Sites (15)

ICO Badalona-Hospital Universitari Germans Trias i Pujol

Badalona, Barcelona, 08916, Spain

Location

ICO Hospital Universitari de Bellvitge

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

Hospital Universitari Son Espases

Palma de Mallorca, Mallorca, 07198, Spain

Location

Hospital Universitari Son Llatzer

Palma de Mallorca, Mallorca, Spain

Location

Hospital Verge de la Cinta

Tortosa, Tarragona, 43517, Spain

Location

Hospital del Mar

Barcelona, 08003, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 08025, Spain

Location

Hospital Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clinic Barcelona

Barcelona, 08036, Spain

Location

ICO-Girona Hopital Universitari de Girona Dr. Josep Trueta

Girona, 17007, Spain

Location

Hospital Universitari Arnau de Vilanova

Lleida, 25006, Spain

Location

Hospital Universitario Virgen de la Victoria

Málaga, 29010, Spain

Location

ICO Tarragona-Hospital Universitari Joan XXIII

Tarragona, 43007, Spain

Location

Mutua de Terrassa

Terrassa, 08225, Spain

Location

Hospital Clínico Universitario de Valencia

Valencia, 496010, Spain

Location

Related Publications (1)

• Onate G, Pratcorona M, Garrido A, Artigas-Baleri A, Bataller A, Tormo M, Arnan M, Vives S, Coll R, Salamero O, Vall-Llovera F, Sampol A, Garcia A, Cervera M, Avila SG, Bargay J, Ortin X, Nomdedeu JF, Esteve J, Sierra J; Spanish Cooperative Group for the Study and Treatment of Acute Leukemias and Myelodysplasias (CETLAM). Survival improvement of patients with FLT3 mutated acute myeloid leukemia: results from a prospective 9 years cohort. Blood Cancer J. 2023 May 5;13(1):69. doi: 10.1038/s41408-023-00839-1.

  PMID: 37147301 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia

Interventions

Idarubicin; Cytarabine; Granulocyte Colony-Stimulating Factor; pegfilgrastim

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Jorge Sierra, Prof, MD

  Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

  PRINCIPAL INVESTIGATOR

• Jordi Esteve, MD, PhD

  Hospital Clinic of Barcelona

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2020
• First Posted: December 29, 2020
• Study Start: February 1, 2012
• Primary Completion: July 31, 2022
• Study Completion: November 10, 2022
• Last Updated: June 27, 2023

Record last verified: 2023-06

Locations

ES (15)