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

Overview

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)

Interventions

• 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)
• 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

Primary outcome measures

• 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. [Time frame: 36 months]

Secondary outcome measures (4)

• To determine if low intensity therapy improves overall survival [Time frame: 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)) [Time frame: 36 months]
• To determine if low intensity therapy improves patients-reported quality of life [Time frame: 36 months]
• To evaluate the safety of low intensity therapies as compared to high intensity therapies [Time frame: 36 months]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Italy · 27 centers

• Policlinico Sant'Orsola — Bologna
• IRCCS Ospedale Policlinico San Martino — Genova
• IRCCS Ospedale Policlinico San Martino — Genova
• Ospedali Riuniti Villa Sofia - Cervello — Palermo
• Ospedale S.Spirito - ASL Pescara — Pescara
• Ospedale Santa Maria della Misericordia — Perugia
• Ospedale Santa Maria delle Croci — Ravenna
• Policlinico Tor Vergata — Roma
• … and 19 more centers

Germany · 6 centers

• Uniklinik RWTH Aachen — Aachen
• University Hospital Greifswald — Greifswald
• Krankenhaus St. Elisabeth und St. Barbara Halle (Saale) GmbH — Halle
• University Hospital Halle — Halle
• University Hospital of Rostock — Rostock
• Heinrich-Braun-Klinikum gGmbH — Zwickau

Spain · 6 centers

• Hospital General Universitario De Albacete — Albacete
• Hospital General Universitario Dr. Balmis — Alicante
• Hospital Universitari Vall D Hebron — Barcelona
• Hospital Clinico Universitario De Valencia — Valencia
• Consorcio Hospital General Universitario De Valencia — Valencia
• Instituto de Investigación Sanitaria La Fe — Valencia

Czechia · 5 centers

• University Hospital Brno — Brno
• University Hospital Hradec Králové — Hradec Králové
• University Hospital Olomouc — Olomouc
• University Hospital in Ostrava — Ostrava
• University Hospital in Pilsen — Pilsen

Lithuania · 1 center

• The Hospital of Lithuanian University of Health Sciences Kauno Klinikos — Kaunas

Portugal · 1 center

• Hospital de Santa Maria — Lisbon

Romania · 1 center

• Fundeni Clinical Institute — Bucharest

Identifiers

NCT: NCT06713837 · IRST204.07 · 2024-514517-35-00 · 101104421

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗