Clinical trial NCT06356922: Study Assessing RLT Using [177Lu]Lu-PentixaTher for Relapsed/Refractory CXCR4+ Acute Leukemia.
Official title: Phase I/II Study Assessing Radioligand Therapy (RLT) Using [177Lu]Lu-PentixaTher for Relapsed/Refractory CXCR4+ Acute Leukemia.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Acute Leukemia
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
First posted: 2024-04-10
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Safety of RLT using one injection of [177Lu]Lu-PentixaTher
timeFrame: Between Week 4 and Week 6
measure: Tolerance
timeFrame: Between Week 4 and Week 6
Secondary outcomes:
measure: Overall response rate
timeFrame: Between Week 4 and Week 6
measure: Complete response rate
timeFrame: Between Week 4 and Week 6
measure: Overall survival
timeFrame: Month 12
measure: Leukemia-free survival
timeFrame: Month 12
measure: Minimal residual disease
timeFrame: Month 12
measure: Whole-body biodistribution
timeFrame: Between Week 4 and Week 6
measure: Plasma uptake
timeFrame: Between Week 4 and Week 6
measure: Radiation dosimetry
timeFrame: Between Week 4 and Week 6
measure: Renal safety
timeFrame: Month 12
measure: Renal safety
timeFrame: Month 12
measure: Renal safety
timeFrame: Month 12
measure: Renal safety
timeFrame: Month 12
measure: Correlation between different cytokines and toxicity
timeFrame: Month 12
measure: Factors associated response
timeFrame: Month 12
measure: Exploratory outcome measure = Identification of biological biomarkers
timeFrame: Month 12
Other outcomes:
measure: Predictive role of PET/MRI (ancillary study)
timeFrame: Between Week 4 and Week 6
Locations:
city: Bordeaux
country: France
facility: CHU de Bordeaux
state: Gironde
city: Nantes
country: France
facility: CHU de Nantes
state: Loire-Atlantique
city: Angers
country: France
facility: CHU d'Angers
state: Maine et Loire
city: Clermont-Ferrand
country: France
facility: CHU de Clermont-Ferrand
state: Puy de Dôme
Study officials:
References: