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.
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
Meningeal involvement
HIV positive
Active Hepatitis B or C
Active infection within 7 days of starting treatment
Single group
Experimental drug [177Lu]Lu-PentixaTher
DrugInjection of \[177Lu\]Lu-PentixaTher
Safety of RLT using one injection of [177Lu]Lu-PentixaTher
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Tolerance
Tolerance of the RLT will be evaluated by dosimetry studies, especially in terms of renal and hepatic doses delivered
Overall response rate
Response evaluation (CR, CRp and PR) after the infusion of \[177Lu\]Lu-PentixaTher
Complete response rate
Response evaluation (CR, CRp) after the infusion of \[177Lu\]Lu-PentixaTher
Overall survival
Time interval from the date from initial of study treatment (D0) until the date of last follow-up or death
Leukemia-free survival
Time interval from the date of documented complete response (CR, CRp) until the date of last follow-up, death or relapse
Predictive role of PET/MRI (ancillary study)
SUVmax will be recorded in extra-medullary sites of pathological uptake.
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