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

NCT06713837 | Recruiting Phase 3

• 3 other identifiers: IRST204.072024-514517-35-00101104421
• Study Type: interventional
• Target: 339
• Locations: 7 countries
• Sites: 47

Brief Summary

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)

Conditions

Relapse/Recurrence; Acute Myeloid Leukemia

Keywords

Relapsed/Refractory; Acute Myeloid Leukemia; Low Intensity therapy; Pragmatic; Low intervention Clinical trial; Randomized controlled trial; Horizon Europe; Mission Cancer; Diagnosis and treatment

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• To determine if low intensity therapy improves overall survival

  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))

  36 months

• To determine if low intensity therapy improves patients-reported quality of life

  36 months

• To evaluate the safety of low intensity therapies as compared to high intensity therapies

  36 months

Study Arms (2)

Low intensity treatment

EXPERIMENTAL

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

High intensity treatment

ACTIVE COMPARATOR

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

Interventions

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)

High intensity treatment

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

Low intensity treatment

Eligibility Criteria

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

You may qualify if:

• Non-Acute promyelocytic leukemia (APL) AML defined according World Health Organization (WHO) 2022 (or International Consensus Classification (ICC) 2022) criteria
• st 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ospedale Pediatrico Bambin Gesù: collaborator
• Czech Lymphoma Study Group: collaborator
• Fundación Instituto de Estudios de Ciencias de la Salud de Castilla y León: collaborator
• Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS: lead
• Gruppo Italiano Malattie EMatologiche dell'Adulto: collaborator
• 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
• Charite University, Berlin, Germany: 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
• TIMELEX: collaborator

Study Sites (47)

University Hospital Brno

Brno, 625 00, Czechia

RECRUITING

University Hospital Hradec Králové

Hradec Králové, 500 05, Czechia

NOT YET RECRUITING

University Hospital Olomouc

Olomouc, 779 00, Czechia

NOT YET RECRUITING

University Hospital in Ostrava

Ostrava, 708 00, Czechia

NOT YET RECRUITING

University Hospital in Pilsen

Pilsen, 323 00, Czechia

NOT YET RECRUITING

Uniklinik RWTH Aachen

Aachen, 52074, Germany

RECRUITING

University Hospital Greifswald

Greifswald, 17475, Germany

RECRUITING

Krankenhaus St. Elisabeth und St. Barbara Halle (Saale) GmbH

Halle, 06110, Germany

NOT YET RECRUITING

University Hospital Halle

Halle, 06120, Germany

RECRUITING

University Hospital of Rostock

Rostock, 18507, Germany

RECRUITING

Heinrich-Braun-Klinikum gGmbH

Zwickau, 08060, Germany

NOT YET RECRUITING

Policlinico Sant'Orsola

Bologna, BO, 40138, Italy

RECRUITING

IRCCS Ospedale Policlinico San Martino

Genova, GE, 16132, Italy

NOT YET RECRUITING

IRCCS Ospedale Policlinico San Martino

Genova, GE, 16132, Italy

NOT YET RECRUITING

Ospedali Riuniti Villa Sofia - Cervello

Palermo, PA, 90146, Italy

RECRUITING

Ospedale S.Spirito - ASL Pescara

Pescara, PE, 65124, Italy

NOT YET RECRUITING

Ospedale Santa Maria della Misericordia

Perugia, PG, 06156, Italy

RECRUITING

Ospedale Santa Maria delle Croci

Ravenna, RA, 48121, Italy

RECRUITING

Policlinico Tor Vergata

Roma, RM, 00133, Italy

RECRUITING

Policlinico Umberto I

Roma, RM, 00161, Italy

RECRUITING

AOU Città della Salute e della Scienza di Torino

Torino, TO, 10126, Italy

RECRUITING

A. O. Ordine Mauriziano

Torino, TO, 10128, Italy

RECRUITING

Azienda Ospedaliero Universitaria Delle Marche

Ancona, 60126, Italy

NOT YET RECRUITING

ASST degli Spedali Civili

Brescia, 25123, Italy

RECRUITING

ASST Valle Olonda

Busto Arsizio, 21052, Italy

RECRUITING

Istituto Oncologico Veneto IRCCS

Castelfranco Veneto, 31033, Italy

RECRUITING

AOU Careggi

Florence, 50019, Italy

RECRUITING

IRST Istituto Romagnolo per lo Studio dei Tumori Dino Amadori

Meldola, 47014, Italy

RECRUITING

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

RECRUITING

ASST Grande Ospedale Metropolitano Niguarda

Milan, 20162, Italy

NOT YET RECRUITING

Azienda Ospedaliera di Rilievo Nazionale Antonio Cardarelli

Naples, 80131, Italy

NOT YET RECRUITING

Azienda Ospedale-Università Padova

Padova, 35100, Italy

RECRUITING

Fondazione IRCCS Policlinico San Matteo

Pavia, 27100, Italy

NOT YET RECRUITING

Azienda Unita Sanitaria Locale Di Piacenza

Piacenza, 29121, Italy

NOT YET RECRUITING

Ospedale Infermi

Rimini, 47923, Italy

RECRUITING

Casa Sollievo Della Sofferenza

San Giovanni Rotondo, 71013, Italy

NOT YET RECRUITING

Azienda Ospedaliero-Universitaria Senese

Siena, 53100, Italy

NOT YET RECRUITING

Ospedale San Bortolo

Vicenza, 36100, Italy

RECRUITING

The Hospital of Lithuanian University of Health Sciences Kauno Klinikos

Kaunas, 50161, Lithuania

RECRUITING

Hospital de Santa Maria

Lisbon, 1649-035, Portugal

RECRUITING

Fundeni Clinical Institute

Bucharest, 022328, Romania

RECRUITING

Hospital General Universitario De Albacete

Albacete, 02006, Spain

NOT YET RECRUITING

Hospital General Universitario Dr. Balmis

Alicante, 03010, Spain

NOT YET RECRUITING

Hospital Universitari Vall D Hebron

Barcelona, 08035, Spain

NOT YET RECRUITING

Hospital Clinico Universitario De Valencia

Valencia, 46010, Spain

NOT YET RECRUITING

Consorcio Hospital General Universitario De Valencia

Valencia, 46014, Spain

NOT YET RECRUITING

Instituto de Investigación Sanitaria La Fe

Valencia, 46026, Spain

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Recurrence; Disease

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Giovanni Martinelli, MD, Prof

  University of Bologna

  STUDY CHAIR

Central Study Contacts

Oriana Nanni

CONTACT

+39 0543739100; cc.ubsc@irst.emr.it

Impact-aml coord Impact-aml coord

CONTACT

impact-aml@irst.emr.it

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 27, 2024
• First Posted: December 3, 2024
• Study Start: February 27, 2025
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028
• Last Updated: April 8, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

ES (6); CZ (5); PT (1); LI (1); RO (1); IT (27); DE (6)