This is a multicenter, randomized, open-label, pragmatic low intervention clinical trial comparing high intensity reinduction chemotherapy with low intensity therapies in 1st or 2nd relapse Acute Myeloid Leukemia. The study is funded by European Commission (HORIZON-MISS-2022-CANCER-01-03, Project ID 101104421)
Non-Acute promyelocytic leukemia (APL) AML defined according World Health Organization (WHO) 2022 (or International Consensus Classification (ICC) 2022) criteria
1st or 2nd relapse or refractory according to European leukemia Network (ELN) 2022
Patient is clinically candidate to both low intensity therapy and high dose chemotherapy in the opinion of the physician
Both low intensity therapy and high dose chemotherapy to which patient is candidate are available and can be provided as per local practice
Known contraindication to the study drug that will be selected by the treating physician within the list of high or low intensity treatment, according to most update version of Summary of Product Characteristics (SmPC) (e.g. hypersensitivity, allergy, organ failure precluding treatment)
Participation in another clinical trial with any investigational agents within 14 days or 5 drug half-lives (whatever comes first) prior to randomization
Active infections or other clinical conditions that in the opinion of the investigator make the patient ineligible to receive study treatment.
Parallel
High intensity therapies
Drug* High and intermediate dose Cytarabine * Mitoxantrone - Etoposide - Cytarabine (MEC) * fludarabine - cytarabine - idarubicin - G-CSF (FLAG-IDA) * cladribine - high dose cytarabine (2CDA+HDAraC) * mitoxantrone - intermediate dose cytarabine (MiDAC) * fludarabine - amsacrine - cytarabine (FLAMSA) * Mitoxantrone - Intermediate-dose Cytarabine (HAM) * 3+7 (cytarabine and daunorubicine or idarubicine)
Low intensity therapies
Drug* Venetoclax+hypomethylating agent (decitabine, azacitidine) * Venetoclax+low dose cytarabine * Gilteritinib alone or in combination with low dose hypomethylating agent or low dose cytarabine * 2CDA 5mg/sqm + low dose cytarabine * Glasdegib+low dose cytarabine * Ivosidenib alone or in combination with low dose hypomethylating agent or low dose cytarabine * Single agent Gemtuzumab or Gemtuzumab in combination with alone or in combination with low dose hypomethylating agent or low dose cytarabine
To determine in R/R AML patients the clinical benefit of low intensity therapy as shown by event-free survival compared to high intensity therapy.
Event-free survival defined as time from randomization to treatment failure, hematologic relapse from CR/CRh/Cri or death from any cause, whichever occurs first.
To determine if low intensity therapy improves overall survival
Overall survival, defined as time from randomization to the date of death from any cause.
To determine if low intensity therapy improves the overall response (Complete response (CR)/CR with partial hematologic recovery(CRh)/CR with incomplete hematologic recovery(CRi),morphologic leukemia-free state(MLFS))
Overall response rate (CR/CRh/CRi, MLFS) as the best assessment of response during the study treatment and the overall study cohort.
To determine if low intensity therapy improves patients-reported quality of life
Change in Hematologic Malignancy-Patient-Reported Outcome (HM-PRO) A-total as defined by the HM-PRO questionnaire between screening and end of treatment assessment.
To evaluate the safety of low intensity therapies as compared to high intensity therapies
Proportion of patients experiencing adverse events.
Click on the lead sponsor to view all of their trials.
Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS
Lead sponsor
Hospital Vall d'Hebron
Collaborator
Cyprus Institute of Neurology and Genetics
Collaborator
European Leukemia Net
Collaborator
Fundacion Para La Investigacion Hospital La Fe
Collaborator
Ostdeutsche Studiengruppe Haematologie Und Onkologie e.V.
Collaborator
Ospedale Pediatrico Bambin Gesù
Collaborator
Czech Lymphoma Study Group
Collaborator
Charite University, Berlin, Germany
Collaborator
Fundación Instituto de Estudios de Ciencias de la Salud de Castilla y León
Collaborator
University of Bologna
Collaborator
Hannover Medical School
Collaborator
German Society for Pediatric Oncology and Hematology GPOH gGmbH
Collaborator
Toscana Life Sciences Sviluppo s.r.l.
Collaborator
Lithuanian University of Health Sciences
Collaborator
Gruppo Italiano Malattie EMatologiche dell'Adulto
Collaborator
TIMELEX
Collaborator