Acute Myeloid Leukemia, Relapse/Recurrence
Conditions
Keywords
Relapsed/Refractory, Acute Myeloid Leukemia, Low Intensity therapy, Pragmatic, Low intervention Clinical trial, Randomized controlled trial, Horizon Europe, Mission Cancer, Diagnosis and 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)
Interventions
DRUGHigh 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)
DRUGLow 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
Sponsors
Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS
Hospital Vall d'Hebron
Cyprus Institute of Neurology and Genetics
European Leukemia Net
Fundacion Para La Investigacion Hospital La Fe
Ostdeutsche Studiengruppe Haematologie Und Onkologie e.V.
Ospedale Pediatrico Bambin Gesù
Czech Lymphoma Study Group
Charite University, Berlin, Germany
Fundación Instituto de Estudios de Ciencias de la Salud de Castilla y León
University of Bologna
Hannover Medical School
German Society for Pediatric Oncology and Hematology GPOH gGmbH
Toscana Life Sciences Sviluppo s.r.l.
Lithuanian University of Health Sciences
Gruppo Italiano Malattie EMatologiche dell'Adulto
TIMELEX
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Czechia, Germany, Italy, Lithuania, Portugal, Romania, Spain
Contacts
CONTACTOriana Nanni
CONTACTImpact-aml coord Impact-aml coord
STUDY_CHAIRGiovanni Martinelli, MD, Prof
University of Bologna
Outcome results
None listed