Clinical trial NCT06713837: IMPACT-AML: A Randomized Pragmatic Clinical Trial for Relapsed or Refractory Acute Myeloid Leukemia.
Official title: IMPACT-AML: A Randomized Pragmatic Clinical Trial for Relapsed or Refractory Acute Myeloid Leukemia. IMPACT-AML RPCT
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Acute Myeloid Leukemia
Relapse/Recurrence
Keywords: Relapsed/Refractory
Acute Myeloid Leukemia
Low Intensity therapy
Pragmatic
Low intervention Clinical trial
Randomized controlled trial
Horizon Europe
Mission Cancer
Diagnosis and treatment
Lead sponsor: Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS
Sponsor class: OTHER
Collaborators: name: Hospital Vall d'Hebron
name: Cyprus Institute of Neurology and Genetics
name: European Leukemia Net
name: Fundacion Para La Investigacion Hospital La Fe
name: Ostdeutsche Studiengruppe Haematologie Und Onkologie e.V.
name: Ospedale Pediatrico Bambin Gesù
name: Czech Lymphoma Study Group
name: Charite University, Berlin, Germany
name: Fundación Instituto de Estudios de Ciencias de la Salud de Castilla y León
name: University of Bologna
name: Hannover Medical School
name: German Society for Pediatric Oncology and Hematology GPOH gGmbH
name: Toscana Life Sciences Sviluppo s.r.l.
name: Lithuanian University of Health Sciences
name: Gruppo Italiano Malattie EMatologiche dell'Adulto
name: TIMELEX
First posted: 2024-12-03
Enrollment: 339
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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)

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)

Eligibility criteria: 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.

Primary outcomes:
measure: 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.
timeFrame: 36 months
Secondary outcomes:
measure: To determine if low intensity therapy improves overall survival
timeFrame: 36 months
measure: 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))
timeFrame: 36 months
measure: To determine if low intensity therapy improves patients-reported quality of life
timeFrame: 36 months
measure: To evaluate the safety of low intensity therapies as compared to high intensity therapies
timeFrame: 36 months
Other outcomes:
Locations:
city: Brno
country: Czechia
facility: University Hospital Brno
city: Hradec Králové
country: Czechia
facility: University Hospital Hradec Králové
city: Olomouc
country: Czechia
facility: University Hospital Olomouc
city: Ostrava
country: Czechia
facility: University Hospital in Ostrava
city: Plzen
country: Czechia
facility: University Hospital in Pilsen
city: Greifswald
country: Germany
facility: University Hospital Greifswald
city: Halle
country: Germany
facility: University Hospital Halle
city: Rostock
country: Germany
facility: University Hospital of Rostock
city: Bologna
country: Italy
facility: Policlinico Sant'Orsola
state: BO
city: Genova
country: Italy
facility: IRCCS Ospedale Policlinico San Martino
state: GE
city: Genova
country: Italy
facility: IRCCS Ospedale Policlinico San Martino
state: GE
city: Palermo
country: Italy
facility: Ospedali Riuniti Villa Sofia - Cervello
state: PA
city: Pescara
country: Italy
facility: Ospedale S.Spirito - ASL Pescara
state: PE
city: Perugia
country: Italy
facility: Ospedale Santa Maria della Misericordia
state: PG
city: Ravenna
country: Italy
facility: Ospedale Santa Maria delle Croci
state: RA
city: Roma
country: Italy
facility: Policlinico Tor Vergata
state: RM
city: Roma
country: Italy
facility: Policlinico Umberto I
state: RM
city: Torino
country: Italy
facility: AOU Città della Salute e della Scienza di Torino
state: TO
city: Torino
country: Italy
facility: A. O. Ordine Mauriziano
state: TO
city: Brescia
country: Italy
facility: ASST degli Spedali Civili
city: Busto Arsizio
country: Italy
facility: ASST Valle Olonda
city: Castelfranco Veneto
country: Italy
facility: Istituto Oncologico Veneto IRCCS
city: Firenze
country: Italy
facility: AOU Careggi
city: Meldola
country: Italy
facility: IRST Istituto Romagnolo per lo Studio dei Tumori Dino Amadori
city: Milano
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
city: Milano
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda
city: Napoli
country: Italy
facility: Azienda Ospedaliera di Rilievo Nazionale Antonio Cardarelli
city: Padova
country: Italy
facility: Azienda Ospedale-Università Padova
city: Rimini
country: Italy
facility: Ospedale Infermi
city: Vicenza
country: Italy
facility: Ospedale San Bortolo
city: Kaunas
country: Lithuania
facility: The Hospital of Lithuanian University of Health Sciences Kauno Klinikos
city: Lisboa
country: Portugal
facility: Hospital de Santa Maria
city: Valencia
country: Spain
facility: Instituto de Investigación Sanitaria La Fe
Study officials:
affiliation: University of Bologna
name: Giovanni Martinelli, MD, Prof
role: STUDY_CHAIR
References: