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

Phase 3

Recruiting

• Conditions: Acute Myeloid Leukemia; Relapse/Recurrence
• Interventions: Drug: Low intensity therapies; Drug: High intensity therapies

• Registration Number: NCT06713837
• Lead Sponsor: Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS

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)

Study Timeline

• Study First Submitted: 2024-11-27
• Study First Submitted QC: 2024-11-27
• Study First Posted: 2024-12-03
• Study Start: 2025-02-27
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-28
• Last Update Posted: 2025-04-29
• Primary Completion: 2028-01
• Study Completion: 2028-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 339

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Low intensity treatment	Low intensity therapies	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
High intensity treatment	High intensity therapies	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.

Primary Outcome Measures

Name	Time	Method
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.	36 months	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.

Secondary Outcome Measures

Name	Time	Method
To determine if low intensity therapy improves overall survival	36 months	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))	36 months	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	36 months	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	36 months	Proportion of patients experiencing adverse events.

Trial Locations

Locations (21)

University Hospital Hradec Králové; 🇨🇿 Hradec Králové, Czechia

University Hospital Brno; 🇨🇿 Brno, Czechia

University Hospital Olomouc; 🇨🇿 Olomouc, Czechia

University Hospital in Ostrava; 🇨🇿 Ostrava, Czechia

University Hospital in Pilsen; 🇨🇿 Plzen, Czechia

University Hospital Greifswald; 🇩🇪 Greifswald, Germany

University Hospital Halle; 🇩🇪 Halle, Germany

University Hospital of Rostock; 🇩🇪 Rostock, Germany

Policlinico Sant'Orsola; 🇮🇹 Bologna, BO, Italy

IRCCS Ospedale Policlinico San Martino; 🇮🇹 Genova, GE, Italy

Ospedali Riuniti Villa Sofia - Cervello; 🇮🇹 Palermo, PA, Italy

Ospedale S.Spirito - ASL Pescara; 🇮🇹 Pescara, PE, Italy

Ospedale Santa Maria della Misericordia; 🇮🇹 Perugia, PG, Italy

Ospedale Santa Maria delle Croci; 🇮🇹 Ravenna, RA, Italy

Policlinico Tor Vergata; 🇮🇹 Roma, RM, Italy

Policlinico Umberto I; 🇮🇹 Roma, RM, Italy

AOU Città della Salute e della Scienza di Torino; 🇮🇹 Torino, TO, Italy

A. O. Ordine Mauriziano; 🇮🇹 Torino, TO, Italy

IRST Istituto Romagnolo per lo Studio dei Tumori Dino Amadori; 🇮🇹 Meldola, Italy

The Hospital of Lithuanian University of Health Sciences Kauno Klinikos; 🇱🇹 Kaunas, Lithuania

Instituto de Investigación Sanitaria La Fe; 🇪🇸 Valencia, Spain