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NCT Number: NCT04687098

Risk-adapted Therapy for Primary Acute Myeloid Leukemia

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.

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Key information

Conditions

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

Age range

17 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

ICO Badalona-Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Idarubicin

Drug

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

Other names: Ida

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.

Other names: HDAC

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.

Other names: Pegfilgrastim

Allogeneic matched or unrelated donor transplant.

Procedure

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

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.

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.

Other names: MRD

Primary outcomes

  1. Complete remission rate (CRR)

    Time frame: 2 months

    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. Disease free survival (DFS)

    Time frame: 4 years

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

  3. Relapse rate (RR)

    Time frame: 4 years

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

Secondary outcomes

  1. Feasibility of treatment completion

    Time frame: 4 years

    Increase the number of patients who complete all treatment phases

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

    Time frame: 4 years

    Evaluate the feasibility of the consolidation treatments in the different risk groups by comparison of overall survival (OS), RR and DFS.

  3. Feasibility of centralized monitoring of measurable residual disease (MRD)

    Time frame: 4 years

    Survival outcomes in positive vs negative MRD patients. Number of patients with modified risk due to positive MRD.

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

    Time frame: 4 years

    Comparison of CRR, OS, RR and DFS

Sponsors and collaborators

Lead sponsor

Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias

Other

Registry information

Official study title

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

Important dates

Study start
2012
Primary completion
2022
Study completion
2022
First posted
Dec 29, 2020
Registry last updated
Jun 27, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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