IMPACT-AML: A Randomized Pragmatic Clinical Trial for Relapsed or Refractory Acute Myeloid Leukemia. (IMPACT-AML)

IMPACT-AML: A Randomized Pragmatic Clinical Trial for Relapsed or Refractory Acute Myeloid Leukemia. IMPACT-AML RPCT

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)

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia; Relapse/Recurrence
• Intervention / Treatment: Drug: Low intensity therapies; Drug: High intensity therapies

Detailed Description

Thanks to recent advantages and results that demonstrate that low-intensity rescues may be quantitatively comparable to chemotherapy, novel personalized therapies are being slowly integrated into the treatment options of R/R AML. These new strategies, for the high interpatient variability, for the different cross-country reimbursement, for the school of thinking of treatment physicians, will wait decades to be proficiently compared with standard chemotherapy in the R/R setting, especially because most of the novel drugs are being pushed by the companies in the front-line (a setting that still has a large room for improvements). In IMPACT-AML RPCT, low-intensity therapies will be compared with high intensity chemotherapy rescue following a pragmatic, clinical-oriented approach. The study is funded by European Commission (HORIZON-MISS-2022-CANCER-01-03, Project ID 101104421)

• Study Type: Interventional
• Enrollment (Estimated): 339
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Impact-aml coord Impact-aml coord; Email: impact-aml@irst.emr.it
• Study Contact Backup: Name: Oriana Nanni; Phone Number: +39 0543739100; Email: cc.ubsc@irst.emr.it

Study Locations

• Czechia
  • Brno, Czechia, 625 00
    • Recruiting
    • University Hospital Brno
    • Contact: Jiri Mayer, Prof.
  • Hradec Králové, Czechia, 500 05
    • Not yet recruiting
    • University hospital Hradec Králové
    • Contact: Pavel Žák, MD
  • Olomouc, Czechia, 779 00
    • Not yet recruiting
    • University Hospital Olomouc
    • Contact: Tomáš Szotkowski, MD
  • Ostrava, Czechia, 708 00
    • Not yet recruiting
    • University Hospital in Ostrava
    • Contact: Zdeněk Kořístek,, MD
  • Pilsen, Czechia, 323 00
    • Recruiting
    • University Hospital in Pilsen
    • Contact: Pavel Jindra, MD
• Germany
  • Aachen, Germany, 52074
    • Recruiting
    • Uniklinik RWTH Aachen
    • Contact: Martina Crysandt, MD
  • Greifswald, Germany, 17475
    • Recruiting
    • University Hospital Greifswald
    • Contact: Adrian Schwarzer, MD
  • Halle, Germany, 06120
    • Recruiting
    • University Hospital Halle
    • Contact: Judith Schaffrath, MD
  • Halle, Germany, 06110
    • Recruiting
    • Krankenhaus St. Elisabeth und St. Barbara Halle (Saale) GmbH
    • Contact: Kinga Ligeti, MD
  • Rostock, Germany, 18507
    • Recruiting
    • University Hospital of Rostock
    • Contact: Christian Junghanß, MD
  • Zwickau, Germany, 08060
    • Recruiting
    • Heinrich-Braun-Klinikum gGmbH
    • Contact: Sara Hilber, MD
• Italy
  • Ancona, Italy, 60126
    • Recruiting
    • Azienda Ospedaliero Universitaria delle Marche
    • Contact: Lorenzo Brunetti, MD
  • Brescia, Italy, 25123
    • Recruiting
    • ASST degli Spedali Civili
    • Contact: Erika Borlenghi, MD
  • Busto Arsizio, Italy, 21052
    • Recruiting
    • ASST Valle Olonda
    • Contact: Elisabetta Todisco, MD
  • Castelfranco Veneto, Italy, 31033
    • Recruiting
    • Istituto Oncologico Veneto IRCCS
    • Contact: Alessandra Sperotto, MD
  • Florence, Italy, 50019
    • Recruiting
    • AOU Careggi
    • Contact: Francesco Mannelli, MD
  • Meldola, Italy, 47014
    • Recruiting
    • IRST Istituto Romagnolo per lo Studio dei Tumori Dino Amadori
    • Contact: Maria Benedetta Giannini, MD
  • Milan, Italy, 20122
    • Recruiting
    • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
    • Contact: Nicola Stefano Fracchiolla, MD
  • Milan, Italy, 20162
    • Not yet recruiting
    • ASST Grande Ospedale Metropolitano Niguarda
    • Contact: Valentina Mancini, MD
  • Naples, Italy, 80131
    • Not yet recruiting
    • Azienda Ospedaliera di Rilievo Nazionale Antonio Cardarelli
    • Contact: Mario Annunziata, MD
  • Padova, Italy, 35100
    • Recruiting
    • Azienda Ospedale-Università Padova
    • Contact: Federica Lessi, MD
  • Pavia, Italy, 27100
    • Not yet recruiting
    • Fondazione IRCCS Policlinico San Matteo
    • Contact: Patrizia Zappasodi, MD
  • Piacenza, Italy, 29121
    • Not yet recruiting
    • Azienda Unita Sanitaria Locale Di Piacenza
    • Contact: Lara Pochintesta, MD
  • Rimini, Italy, 47923
    • Recruiting
    • Ospedale Infermi
    • Contact: Anna Maria Mianulli, MD
  • San Giovanni Rotondo, Italy, 71013
    • Not yet recruiting
    • Casa Sollievo Della Sofferenza
    • Contact: Giovanni Rossi, MD
  • Siena, Italy, 53100
    • Not yet recruiting
    • Azienda Ospedaliero-Universitaria Senese
    • Contact: Monica Bocchia, MD
  • Vicenza, Italy, 36100
    • Recruiting
    • Ospedale San Bortolo
    • Contact: Davide Facchinelli, MD
  • BO
    • Bologna, BO, Italy, 40138
      • Recruiting
      • Policlinico Sant'Orsola
      • Contact: Antonio Curti, MD
  • GE
    • Genova, GE, Italy, 16132
      • Recruiting
      • IRCCS Ospedale Policlinico San Martino
      • Contact: Fabio Guolo, MD
    • Genova, GE, Italy, 16132
      • Not yet recruiting
      • IRCCS Ospedale Policlinico San Martino
      • Contact: Marica Laurino, MD
  • PA
    • Palermo, PA, Italy, 90146
      • Recruiting
      • Ospedali Riuniti Villa Sofia - Cervello
      • Contact: Antonino Mulè, MD
  • PE
    • Pescara, PE, Italy, 65124
      • Not yet recruiting
      • Ospedale S.Spirito - ASL Pescara
      • Contact: Prassede Salutari
  • PG
    • Perugia, PG, Italy, 06156
      • Recruiting
      • Ospedale Santa Maria Della Misericordia
      • Contact: Maria Paola Martelli, MD
  • RA
    • Ravenna, RA, Italy, 48121
      • Recruiting
      • Ospedale Santa Maria delle Croci
      • Contact: Giovanni Marconi, MD
  • RM
    • Roma, RM, Italy, 00133
      • Recruiting
      • Policlinico Tor Vergata
      • Contact: Adriano Venditti, MD
    • Roma, RM, Italy, 00161
      • Recruiting
      • Policlinico Umberto I
      • Contact: Saveria Capria, MD
  • TO
    • Torino, TO, Italy, 10126
      • Recruiting
      • AOU Città della Salute e della Scienza di Torino
      • Contact: Ernesta Audisio, MD
    • Torino, TO, Italy, 10128
      • Recruiting
      • A. O. Ordine Mauriziano
      • Contact: Daniela Cilloni, MD
• Lithuania
  • Kaunas, Lithuania, 50161
    • Recruiting
    • The Hospital of Lithuanian University of Health Sciences Kauno Klinikos
    • Contact: Rolandas Gerbutavičius, MD
• Portugal
  • Lisbon, Portugal, 1649-035
    • Recruiting
    • Hospital de Santa Maria
    • Contact: Joana Brioso Infante, MD
• Romania
  • Bucharest, Romania, 022328
    • Recruiting
    • Fundeni Clinical Institute
    • Contact: Daniel Coriu, MD
• Spain
  • Albacete, Spain, 02006
    • Not yet recruiting
    • Hospital General Universitario de Albacete
    • Contact: Jesús Lorenzo Algarra, MD
  • Alicante, Spain, 03010
    • Not yet recruiting
    • Hospital General Universitario Dr. Balmis
    • Contact: Carmen Botella Prieto, MD
  • Barcelona, Spain, 08035
    • Not yet recruiting
    • Hospital Universitari Vall d Hebron
    • Contact: Olga Salamero, MD
  • Valencia, Spain, 46010
    • Not yet recruiting
    • Hospital Clínico Universitario de Valencia
    • Contact: Maria del Mar Tormo Díaz, MD
  • Valencia, Spain, 46026
    • Recruiting
    • Instituto de Investigación Sanitaria La Fe
    • Contact: Pau Montesinos, MD
  • Valencia, Spain, 46014
    • Not yet recruiting
    • Consorcio Hospital General Universitario de Valencia
    • Contact: Armando Mena Duran, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

• No specific treatment protocol can be rationally considered better suited to patient needs.This specifically include, but is not limited to:

  i) the availability of a drug that is already demonstrated superior to comparator arm and can be considered the only standard of care ii) specific contraindications related to fitness or any medical conditions that deem to avoid one of the two arms of this randomization iii) patient willingness to avoid one of the two arm of this randomization iv) lack of social support that make unfeasible one of the two arm of this randomization

• Male or Female, aged>18 years
• Eastern Cooperative Oncology Group (ECOG) performance status <4
• A female participant is eligible to participate if she is not pregnant and not breastfeeding. If Women of childbearing potential (WOCBP), negative serum pregnancy test within 14 days of starting treatment must be obtained. WOCBP must adopt highly effective birth control methods, according to guideline "Recommendation related to contraception and pregnancy testing in clinical trials". Male patient and his female partner who is of childbearing potential must use 2 methods of birth control (a condom as a barrier method of contraception and one of the highly effective birth control methods, according to guideline "Recommendation related to contraception and pregnancy testing in clinical trials". Use of- and compliance to- birth control methods are required beginning at the screening visit and continuing until 6 months following last treatment with study drug.
• Participant is willing and able to give informed consent for participation in the study

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low intensity treatment; Low intensity treatments are based on the single agent use of innovative and target drugs or their combination with other target drugs and less-toxic agents in doublets or triplets. Administration of low intensity therapies in combination with antibodies or target agents would be included in this cohort	Drug: Low intensity therapies; 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
Active Comparator: High intensity treatment; Intensive treatment of leukemia is based on high dose of chemotherapy agents. Administration of high-dose chemotherapy in combination with antibodies or target agents would be included in this cohort.	Drug: High intensity therapies; 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine if low intensity therapy improves overall survival	Overall survival, defined as time from randomization to the date of death from any cause.	36 months
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.	36 months
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.	36 months
To evaluate the safety of low intensity therapies as compared to high intensity therapies	Proportion of patients experiencing adverse events.	36 months

Collaborators and Investigators

• Sponsor: Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS
• Collaborators: Charite University, Berlin, Germany; University of Bologna; Hannover Medical School; Lithuanian University of Health Sciences; Fundación Instituto de Estudios de Ciencias de la Salud de Castilla y León; Gruppo Italiano Malattie EMatologiche dell'Adulto; Hospital Vall d'Hebron; Fundacion Para La Investigacion Hospital La Fe; Toscana Life Sciences Sviluppo s.r.l.; Cyprus Institute of Neurology and Genetics; Czech Lymphoma Study Group; European Leukemia Net; Ospedale Pediatrico Bambin Gesù; German Society for Pediatric Oncology and Hematology GPOH gGmbH; TIMELEX; Ostdeutsche Studiengruppe Haematologie Und Onkologie e.V.
• Investigators: Study Chair: Giovanni Martinelli, MD, Prof, University of Bologna

Study record dates

Study Major Dates

• Study Start (Actual): February 27, 2025
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: November 27, 2024
• First Submitted That Met QC Criteria: November 27, 2024
• First Posted (Actual): December 3, 2024

Study Record Updates

• Last Update Posted (Actual): June 10, 2026
• Last Update Submitted That Met QC Criteria: June 9, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Acute Myeloid Leukemia; Randomized controlled trial; Relapsed/Refractory; Pragmatic; Low Intensity therapy; Low intervention Clinical trial; Horizon Europe; Mission Cancer; Diagnosis and treatment
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease Attributes; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Leukemia; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Recurrence; Leukemia, Myeloid, Acute; Disease
• Other Study ID Numbers: IRST204.07; 2024-514517-35-00 (Ctis); 101104421 (Other Grant/Funding Number: European Commission)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No