- ICH GCP
- US Clinical Trials Registry
- Clinical Trial 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
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.
Study Overview
Status
Conditions
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Jorge Sierra, Prof, MD
- Phone Number: 5649 +34935565649
- Email: jsierra@santpau.cat
Study Contact Backup
- Name: Ana Garrido, MD
- Phone Number: 5649 +34935565649
- Email: agarridod@santpau.cat
Study Locations
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Barcelona, Spain, 08003
- Hospital del Mar
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Barcelona, Spain, 08035
- Hospital Vall d'Hebron
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Barcelona, Spain, 08025
- Hospital de la Santa Creu i Sant Pau
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Barcelona, Spain, 08036
- Hospital Clinic Barcelona
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Girona, Spain, 17007
- ICO-Girona Hopital Universitari de Girona Dr. Josep Trueta
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Lleida, Spain, 25006
- Hospital Universitari Arnau de Vilanova
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Malaga, Spain, 29010
- Hospital Universitario Virgen de la Victoria
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Tarragona, Spain, 43007
- ICO Tarragona-Hospital Universitari Joan XXIII
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Terrassa, Spain, 08225
- Mutua de Terrassa
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Valencia, Spain, 496010
- Hospital Clínico Universitario de Valencia
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Barcelona
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Badalona, Barcelona, Spain, 08916
- ICO Badalona-Hospital Universitari Germans Trias I Pujol
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Hospitalet de Llobregat, Barcelona, Spain, 08907
- ICO Hospital Universitari de Bellvitge
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Mallorca
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Palma de Mallorca, Mallorca, Spain, 07198
- Hospital Universitari Son Espases
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Palma de Mallorca, Mallorca, Spain
- Hospital Universitari Son Llatzer
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Tarragona
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Tortosa, Tarragona, Spain, 43517
- Hospital Verge de la Cinta
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Other: Risk-adapted postremission treatment.
Induction (idarubicin, cytarabine), first consolidation (high dose cytarabine), risk- stratification: allogeneic matched related or unrelated donor transplant vs. consolidation courses.
|
12 mg/m2/day; intravenous, administration at induction phase, days 1 to 3.
Other Names:
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:
Other Names:
To be performed in patients in the intermediate or adverse risk groups.
To be considered in patients in the intermediate risk group without an available allogeneic donor and negative measurable residual disease, per center decision.
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:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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 months
|
Disease free survival (DFS)
Time Frame: 4 years
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Analyze the disease free survival in the whole cohort of AML patients.
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4 years
|
Relapse rate (RR)
Time Frame: 4 years
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Analyze the relapse rate of all patients achieving remission with intensive induction followed by risk-adapted consolidation strategies.
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4 years
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Feasibility of treatment completion
Time Frame: 4 years
|
Increase the number of patients who complete all treatment phases
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4 years
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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.
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4 years
|
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.
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4 years
|
Comparison of global outcomes with previous protocol (AML-03) and other published protocols.
Time Frame: 4 years
|
Comparison of CRR, OS, RR and DFS
|
4 years
|
Collaborators and Investigators
Investigators
- Principal Investigator: 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
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- AML-12
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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