Clinical trial • Phase II • Haematology

asciminib hydrochloride for Chronic myeloid leukaemia (BCR-ABL1+)

Phase II trial of asciminib hydrochloride for Chronic myeloid leukaemia (BCR-ABL1+).

Overview

Trial Therapeutic Area
Haematology
Trial Disease
Chronic myeloid leukaemia (BCR-ABL1+)
Trial Stage
Phase II
Drug Modality
Small molecule
Orphan Drug
Yes

Key dates

Initial CTIS Submission Date
10-12-2024
First CTIS Authorization Date
22-04-2025

Trial design

Asciminib single-agent versus asciminib in combination with nilotinib; investigational products listed include Scemblix (asciminib) and Tasigna (nilotinib). Specific arm doses and schedules are not specified in the available Part I/Part II information.-controlled Phase II trial across 43 sites in Spain, Italy.

Comparator
Asciminib single-agent versus asciminib in combination with nilotinib; investigational products listed include Scemblix (asciminib) and Tasigna (nilotinib). Specific arm doses and schedules are not specified in the available Part I/Part II information.
Target Sample Size
160

Eligibility

Recruits 160 Vulnerable population not selected; subjects are adults (Age ≥ 18 years). Signed written informed consent is required according to ICH/EU/GCP and national/local laws prior to any study procedure; refusal or impossibility to give informed consent is an exclusion criterion. No assent process for minors is applicable (minors excluded)..

Pregnancy Exclusion
Pregnant or lactating women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
Vulnerable Population
Vulnerable population not selected; subjects are adults (Age ≥ 18 years). Signed written informed consent is required according to ICH/EU/GCP and national/local laws prior to any study procedure; refusal or impossibility to give informed consent is an exclusion criterion. No assent process for minors is applicable (minors excluded).

Inclusion criteria

  • {"criterion_text":"- Cytogenetic and molecular confirmed diagnosis of Ph+ and BCR::ABL1+ CML\n- Age ≥ 18 years\n- Early chronic phase, less than 3 months from diagnosis\n- Evidence at the time of study entry of typical BCR::ABL1 RNA transcripts e13a2 or e14a2 (b2a2 or b3a2), which are required for BCR::ABL international scale reporting\n- Prior treatment with any TKI for 30 days or less; prior treatment with hydroxyurea or anagrelide is allowed\n- ECOG performance status of 0, 1 or 2\n- Adequate end organ function as defined by -Total bilirubin ≤ 1.5 x ULN except for patients with Gilbert’s syndrome who may only be included if total bilirubin ≤ 3.0 x ULN or direct bilirubin ≤ 1.5 x ULN - Aspartate transaminase (AST) ≤ 3.0 x ULN- Alanine transaminase (ALT) ≤ 3.0 x ULN - Serum amylase ≤ 1.5 x ULN - Serum lipase ≤ 1.5 x ULN - Alkaline phosphatase ≤ 2.5 x ULN, unless considered tumor related - Creatinine clearance > 50 ml/min using Cockcroft-Gault formula\n- Signed written informed consent according to ICH/EU/GCP and national local laws prior to any study procedure\n- An effective form of contraception with their sexual partners from enrolment through 30 days after the end of treatment."}

Exclusion criteria

  • {"criterion_text":"- CML in blast phase (BP) or in second chronic phase after previous BP, according to WHO criteria\n- Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection, or gastric bypass surgery)\n- Pregnant or lactating women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.\n- Women of child-bearing potential, unless they are using highly effective methods of contraception during dosing and for 30 days after the end of treatment.\n- Previous treatment with TKIs for more than 30 days\n- Refusal or impossibility to give an informed consent\n- History or current diagnosis of cardiac disease indicating significant risk of safety for patients participating in the study such as uncontrolled or significant cardiac disease, including any of the following: recent myocardial infarction (within last 6 months), uncontrolled congestive heart failure, unstable angina (within last 6 months), clinically significant (symptomatic) cardiac arrhythmias (e.g., sustained ventricular tachycardia, and clinically significant second or third degree AV block without a pacemaker).\n- Severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol (e.g. uncontrolled diabetes, active or uncontrolled infection)\n- History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis\n- History of acute or chronic liver disease\n- History of other active malignancy within 2 years prior to study entry with the exception of previous or concomitant basal cell skin cancer and previous carcinoma in situ treated curatively\n- Known history of Human Immunodeficiency Virus (HIV), Hepatitis B (HBV), or Hepatitis C (HCV) infection. Testing for Hepatitis B surface antigen (HBs Ag) and Hepatitis B core antibody (HBc Ab / anti HBc) will be performed at study entry"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- The primary endpoint is the rate of deep molecular response (MR4) at 2 years; patients with not evaluable molecular analysis may repeat a QPCR analysis in 1 month (25 months from day 1)","definition_or_measurement_approach":"Deep molecular response defined as MR4 at 2 years measured by QPCR on BCR::ABL1 transcripts; patients with non-evaluable molecular analysis may repeat QPCR after 1 month (up to 25 months from day 1)."}

Secondary endpoints

  • {"endpoint_text":"- The rate of sustained MR4 or MR4.5 at 4 years (TFR eligibility) and the proportion of patients free from relapse (BCR::ABL1 transcript < 0.1%) 12 months after treatment discontinuation\n- The rate of major molecular response (MR3) at and by 1, 2, 3, 6, 12, 18 and 24 months, and the rate of MR4 and MR4.5 at and by 1, 2, 3, 4 years\n- The median time to response (MR3, MR4, MR4.5) and the relationship between the time to response (response at milestones) and the TFR eligibility at 4 years and the TFR rate 12 months after discontinuation\n- Outcome measures at 2 and 5 years: overall survival (OS), survival without leukemia-related death, progression-free survival (PFS)\n- Outcome measures at 5 years according to baseline prognostic factors (Sokal and ELTS score, CCA in Ph+ cells, BCR::ABL transcript type, and according to the early response (BCR::ABL transcript level at 3 and 6 months)\n- Incidence and VAF of treatment emergent BCR::ABL1 mutations\n- Incidence and VAF of BL and treatment emergent cancer related somatic mutations and relationship with treatment efficacy, including treatment-free remission and outcome\n- Incidence of hematologic and non-hematologic adverse events\n- Mean HRQoL scores trajectories by the EORTC QLQ-C30 and QLQ-CML24 questionnaires according to treatment arm","definition_or_measurement_approach":"Endpoints measured by molecular response (QPCR BCR::ABL1) at specified timepoints (MR3, MR4, MR4.5), time-to-response medians, survival outcomes (OS, PFS), incidence and variant allele frequency (VAF) of emergent BCR::ABL1 and other somatic mutations, safety via adverse event reporting, and HRQoL via EORTC QLQ-C30 and QLQ-CML24 up to 24 months; specific timepoints and thresholds are as stated per endpoint."}

Recruitment

Planned Sample Size
160
Recruitment Window Months
90
Consent Approach
Signed written informed consent is required according to ICH/EU/GCP and national/local laws prior to any study procedure. Study information and ICF documents are available in Italian, Spanish and English (subject information and informed consent forms listed for ES, EN, IT). Participants are adults (Age ≥ 18 years).

Geography

Total Number Of Sites
43
Total Number Of Participants
160

Spain

Earliest CTIS Part Ii Submission Date
20-02-2025
Latest Decision Or Authorization Date
17-11-2025
Processing Time Days
270
Number Of Sites
15
Number Of Participants
80

Sites

Site Name
Complexo Hospitalario Universitario De Santiago
Department Name
Hematology
Contact Person Name
Manuel Mateo Pérez Encinas
Site Name
Hospital Universitario 12 De Octubre
Department Name
Hematology
Contact Person Name
Gonzalo Carreño Gomez- Tarragona
Site Name
University Clinical Hospital Virgen De La Arrixaca
Department Name
Hematology and Hemotherapy
Contact Person Name
Raùl Perez Lopez
Contact Person Email
raul.perez@carm.es
Site Name
Institut Catala D'oncologia
Department Name
Hematology
Contact Person Name
Blanca Xicoy Cirici
Contact Person Email
bxicoy@iconcologia.net
Site Name
Hospital Universitario Ramon Y Cajal
Department Name
Hematology
Contact Person Name
Valentin Garcia-Gutiérrez
Contact Person Email
jvalentingg@gmail.com
Site Name
Hospital Universitario La Paz
Department Name
Hematology
Contact Person Name
Raquel de Paz Arias
Contact Person Email
depazraquel@gmail.com
Site Name
Hospital Del Mar
Department Name
Hematology
Contact Person Name
Patricia Vélez Tenza
Contact Person Email
patricia.velez.tenza@psmar.cat
Site Name
Institut Catala D'oncologia (Girona)
Department Name
Oncologia
Contact Person Name
Anna Angona Figueras
Site Name
Hospital Universitario De Salamanca
Department Name
Hematology
Contact Person Name
Magdalena Sierra Pacho
Contact Person Email
msierrap@saludcastillayleon.es
Site Name
El Hospital Universitario De Gran Canaria Dr. Negrin
Department Name
Hematology
Contact Person Name
María Teresa Gómez Casares
Site Name
Hospital Universitario Virgen De Las Nieves
Department Name
Hematología y Hemoterapia
Contact Person Name
Jose Manuel Puerta Puerta
Contact Person Email
josepuertahemato@gmail.com
Site Name
Hospital Universitario De Leon
Department Name
Hematology
Contact Person Name
Natalia de las Heras Rodríguez
Contact Person Email
nherasr@saludcastillayleon.es
Site Name
Hospital General Universitario Gregorio Maranon
Department Name
Oncologico y Terapias Avanzadas
Contact Person Name
Santiago Osorio Prendes
Site Name
Hospital Universitario Basurto
Department Name
Hematology
Contact Person Name
Fernando Marco de Lucas
Site Name
Hospital Universitario Y Politecnico La Fe
Department Name
Hematology
Contact Person Name
Elvira Mora Casterá
Contact Person Email
mora_elv@gva.es

Italy

Earliest CTIS Part Ii Submission Date
02-04-2025
Latest Decision Or Authorization Date
27-02-2026
Processing Time Days
331
Number Of Sites
28
Number Of Participants
80

Sites

Site Name
Grande Ospedale Metropolitano Bianchi Melacrino Morelli
Department Name
EMATOLOGIA
Contact Person Name
Matteo Picilli
Contact Person Email
matpicilli@yahoo.it
Site Name
Azienda Ospedaliero-Universitaria Policlinico G. Rodolico-San Marco Di Catania
Department Name
EMATOLOGIA CON TRAPIANTO DEL MIDOLLO OSSEO
Contact Person Name
Uros Markovic
Contact Person Email
urosmarkovic09041989@gmail.com
Site Name
Azienda Ospedaliera Ordine Mauriziano Di Torino
Department Name
DIPARTIMENTO DI SCIENZE CLINICHE E BIOLOGICHE
Contact Person Name
Carmen Fava
Contact Person Email
carmen.fava@unito.it
Site Name
Fondazione IRCCS Policlinico San Matteo
Department Name
UOC EMATOLOGIA
Contact Person Name
Chiara Elena
Contact Person Email
c.elena@smatteo.pv.it
Site Name
Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari
Department Name
U.O. Ematologia con Trapianto
Contact Person Name
Pellegrino Musto
Site Name
Azienda Ospedaliero-Universitaria Maggiore Della Carita
Department Name
SCDU EMATOLOGIA
Contact Person Name
Andrea Patriarca
Contact Person Email
andrea.patriarca@uniupo.it
Site Name
Ospedale San Raffaele S.r.l.
Department Name
EMATOLOGIA E TRAPIANTO MIDOLLO OSSEO
Contact Person Name
Daniele Sannipoli
Contact Person Email
sannipoli.daniele@hsr.it
Site Name
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
Department Name
EMATOLOGIA
Contact Person Name
Alessandra Iurlo
Site Name
Azienda Ospedaliera Universitaria Senese
Department Name
DIPARTIMENTO DI SCIENZE MEDICHE,CHIRURGICHE E NEUROSCIENZE
Contact Person Name
Monica Bocchia
Contact Person Email
bocchia@unisi.it
Site Name
Azienda Ospedaliero-Universitaria Delle Marche
Department Name
MEDICINA INTERNA-SOD CLINICA DI EMATOLOGIA
Contact Person Name
Anna Rita Scortechini
Site Name
Azienda Unita Sanitaria Locale Di Piacenza
Department Name
DIPARTIMENTO DI ONCO-EMATOLOGIA
Contact Person Name
Elena Trabacchi
Contact Person Email
e.trabacchi@ausl.pc.it
Site Name
ULSS3 SERENISSIMA - Ospedale dell'Angelo di Mestre
Department Name
DIPARTIMENTO DI ONCOLOGIA
Contact Person Name
Cristina Skert
Site Name
Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello
Department Name
UOC ONCOEMATOLOGIA
Contact Person Name
Alessandra Malato
Site Name
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Department Name
DIAGNOSTICA PER IMMAGINI, RADIOTERAPIA ONCOLOGICA ED EMATOLOGIA
Contact Person Name
Federica Sorà
Contact Person Email
federica.sora@Unicatt.it
Site Name
Azienda Unita Locale Socio Sanitaria N 8 Berica
Department Name
ONCOLOGIA
Contact Person Name
Davide Facchinelli
Site Name
Azienda Ospedaliera Di Rilievo Nazionale Antonio Cardarelli
Department Name
EMATOLOGIA
Contact Person Name
Mario Annunziata
Site Name
Azienda Ospedaliera Universitaria Gaetano Martino Messina
Department Name
UOC EMATOLOGIA
Contact Person Name
Alessandro Allegra
Contact Person Email
alessandro.allegra@unime.it
Site Name
Azienda Ospedaliero-Universitaria Policlinico Umberto I
Department Name
DIPARTIMENTO DI MEDICINA TRASLAZIONALE E DI PRECISIONE
Contact Person Name
Massimo Breccia
Contact Person Email
massimo.breccia@uniroma1.it
Site Name
Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia
Department Name
EMATOLOGIA
Contact Person Name
Mariella D'Adda
Site Name
Azienda Ospedaliera Universitaria Citta Della Salute E Della Scienza Di Torino
Department Name
ONCOLOGIA
Contact Person Name
Valentina Giai
Contact Person Email
vgiai@cittadellasalute.to.it
Site Name
Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico
Department Name
DIPARTIMENTO MALATTIE ONCOLOGICHE ED EMATOLOGICHE
Contact Person Name
Fausto Castagnetti
Contact Person Email
fausto.castagnetti@unibo.it
Site Name
Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone
Department Name
EMATOLOGIA
Contact Person Name
Marco Santoro
Contact Person Email
santoro.dott@gmail.com
Site Name
Azienda Ospedaliera Universitaria Integrata Verona
Department Name
DIPARTIMENTO DI INGEGNERIA PER L'INNOVAZIONE MEDICA, SEZIONE BIOMEDICINA, AREA EMATOLOGIA
Contact Person Name
Massimiliano Bonifacio
Site Name
Azienda USL IRCCS Di Reggio Emilia
Department Name
DIPARTIMENTO DI ONCOLOGIA E TECNOLOGIE AVANZATE
Contact Person Name
Isabella Capodanno
Contact Person Email
isabella.capodanno@ausl.re.it
Site Name
Azienda Ospedaliera Universitaria Federico II Di Napoli
Department Name
EMATOLOGIA E TRAPIANTO MIDOLLO OSSEO
Contact Person Name
Fabrizio Pane
Contact Person Email
fabrizio.pane@unina.it
Site Name
Azienda Sanitaria Universitaria Friuli Centrale
Department Name
SOC CLINICA EMATOLOGICA
Contact Person Name
Mario Tiribelli
Contact Person Email
mario.tiribelli@uniud.it
Site Name
Azienda Ospedaliera di Padova
Department Name
EMATOLOGIA E IMMUNOLOGIA CLINICA
Contact Person Name
Gianni Binotto
Contact Person Email
gianno.binotto@unipd.it
Site Name
Careggi University Hospital
Department Name
EMATOLOGIA
Contact Person Name
Barbara Scappini

Sponsor

Primary sponsor

Full Name
Fondazione Gimema Franco Mandelli Onlus
Organisation Type
Patient organisation/association
Country Of Registered Address
Italy

Third parties

  • {"country":"Italy","full_name":"Hippocrates Research S.r.l.","duties_or_roles":"code: 1","organisation_type":"Pharmaceutical company"}
  • {"country":"Italy","full_name":"Laboratorio Centro Clinico Unità Operativa di Ematologia","duties_or_roles":"code: 4","organisation_type":"Health care"}
  • {"country":"Spain","full_name":"El Hospital Universitario De Gran Canaria Dr. Negrin","duties_or_roles":"code: 4","organisation_type":"Hospital/Clinic/Other health care facility"}
  • {"country":"Spain","full_name":"Fundacion Teofilo Hernando","duties_or_roles":"codes: 1,12,14,5,8","organisation_type":"Laboratory/Research/Testing facility"}

Co-sponsors

  • Grupo Espanol De Leucemia Mieloide Cronica (GELMC)

Investigational products

Investigational Product Name
Scemblix 40 mg film-coated tablets
Active Substance
asciminib hydrochloride
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
Marketing authorisation EU/1/22/1670/004
Orphan Designation
Yes
Maximum Dose
80 mg/day
Investigational Product Name
Tasigna 150 mg hard capsules
Active Substance
nilotinib
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
Marketing authorisation EU/1/07/422/005
Maximum Dose
600 mg/day
Combination Treatment
Yes

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