Informations générales (source: ClinicalTrials.gov)
Phase I/II Study Assessing Radioligand Therapy (RLT) Using [177Lu]Lu-PentixaTher for Relapsed/Refractory CXCR4+ Acute Leukemia.
Interventional
Phase 1/Phase 2
Nantes University Hospital (Voir sur ClinicalTrials)
octobre 2024
octobre 2027
18 septembre 2025
CXCR4 inhibition may represent a new therapeutic strategy in acute leukemia (AL)
patients, not only by increasing chemosensitivity but also by preventing relapse of the
disease by disruption of the interaction of residual leukemic cells with the bone marrow
niche. Radiolabeled CXCR4 ligands have been developed for PET imaging (68Ga-PentixaFor;
INN: Gallium (68Ga) boclatixafortide) and radioligand therapy (RLT)
([177Lu]Lu-PentixaTher/[90Y]Y-PentixaTher). [177Lu]Lu and [90Y]Y-PentixaTher have been
tested in three multiple myeloma patients in named-patient use with a remarkable efficacy
in 2 patients (Herrmann, 2016). Moreover, feasibility of CXCR4 PET imaging in AML was
reported, providing a framework for future theranostic approaches targeting the
CXCR4/CXCL12-defined leukemia-initiating cell niche (Herhaus, 2016).
Here a Phase I/II study to determine maximal tolerated dose (MTD) of a RLT using
[177Lu]Lu-PentixaTher in relapsed/refractory AL was designed. This will be a standard
phase I/II 3+3 dose escalation study. Five dose levels will be tested, so 6 to 21
patients have to be included in the study.
Etablissements
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CHU d'Angers - 49100 - Angers - Maine Et Loire - France | HUNAULT Mathilde | Contact (sur clinicalTrials) | |||
| CHU de Bordeaux - 33604 - Bordeaux - Gironde - France | DUMAS Pierre-Yves | Contact (sur clinicalTrials) | |||
| CHU de Clermont-Ferrand - 63000 - Clermont-Ferrand - Puy De Dôme - France | MOLUCON Cécile | Contact (sur clinicalTrials) | |||
| CHU de Nantes - 44000 - Nantes - Loire-Atlantique - France | Patrice CHEVALLIER | Contact (sur clinicalTrials) | |||
Critères
Tous
Inclusion Criteria:
- Age ≥ 18 years
- AML/ALL (OMS) with >5% of blasts in bone marrow (with or without extramedullary
localisation)
- CXCR4+ (ratio >2/isotypic control) at the time of pre-inclusion
- All previously treated AML/ALL patients who have experienced relapse or treatment
failure with no alternative treatment
- At least 15 days since previous treatment
- Eastern Cooperative Oncology Group (ECOG) performance status < 2 (Annex 6)
- eGFR ≥ 50 ml/min by MDRD or CKDEPI
- ASAT or ALAT > 5 upper normal value (except in case of documented presence of
leukemia in the liver)
- Serum bilirubin ≤ 30 µmol/l
- Negative pregnancy test documented prior to enrolment (for females of childbearing
potential)
- Agree to use an effective form of contraception with sexual partners throughout
study participation (for female and male patients who are fertile)
- No active cardiac dysfunction (LVEF > 45%)
- DLCO >40%
- Written informed consent
- Be willing and able to comply with scheduled visits and study procedures
- Affiliation with French social security system or beneficiary from such system
- Age ≥ 18 years
- AML/ALL (OMS) with >5% of blasts in bone marrow (with or without extramedullary
localisation)
- CXCR4+ (ratio >2/isotypic control) at the time of pre-inclusion
- All previously treated AML/ALL patients who have experienced relapse or treatment
failure with no alternative treatment
- At least 15 days since previous treatment
- Eastern Cooperative Oncology Group (ECOG) performance status < 2 (Annex 6)
- eGFR ≥ 50 ml/min by MDRD or CKDEPI
- ASAT or ALAT > 5 upper normal value (except in case of documented presence of
leukemia in the liver)
- Serum bilirubin ≤ 30 µmol/l
- Negative pregnancy test documented prior to enrolment (for females of childbearing
potential)
- Agree to use an effective form of contraception with sexual partners throughout
study participation (for female and male patients who are fertile)
- No active cardiac dysfunction (LVEF > 45%)
- DLCO >40%
- Written informed consent
- Be willing and able to comply with scheduled visits and study procedures
- Affiliation with French social security system or beneficiary from such system
- Meningeal involvement
- HIV positive
- Active Hepatitis B or C
- Active infection within 7 days of starting treatment
- Previous or concurrent second malignancy except for adequately treated basal cell
carcinoma of the skin, curatively treated in situ carcinoma of the cervix,
curatively treated solid cancer, with no evidence of disease for at least 1 year
- Any psychological, familial, sociological or geographical condition potentially
hampering compliance with the study protocol and follow-up schedule
- Participation at the same time in another study in which investigational drugs are
used
- Patient with contra-indications to Rhu-EPO, Rhu-GCSF, allopurinol, rasburicase,
anti-histamines and corticosteroids
- Absence of written informed consent
- Pregnant or child breast feeding woman
- Patient under guardianship or trusteeship
- Patient under judicial protection