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Clinical Trial Details — Status: Not yet recruiting

Administrative data

NCT number NCT06356922
Other study ID # RC20_0123
Secondary ID
Status Not yet recruiting
Phase Phase 1/Phase 2
First received
Last updated
Start date May 15, 2024
Est. completion date May 15, 2027

Study information

Verified date March 2024
Source Nantes University Hospital
Contact Patrice CHEVALLIER
Phone 00332 40 08 39 94
Email patrice.chevallier@chu-nantes.fr
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Recruitment information / eligibility

Status Not yet recruiting
Enrollment 21
Est. completion date May 15, 2027
Est. primary completion date May 15, 2027
Accepts healthy volunteers No
Gender All
Age group 18 Years to 100 Years
Eligibility Inclusion Criteria: - Age = 18 years - AML/ALL (OMS) with >5% of blasts in bone marrow (with or without extramedullary localisation) - CXCR4+ expression = 20% of the blast population 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 mmol/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 including Covid infection - 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

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Experimental drug [177Lu]Lu-PentixaTher
Injection of [177Lu]Lu-PentixaTher

Locations

Country Name City State
France CHU d'Angers Angers Maine Et Loire
France CHU de Bordeaux Bordeaux Gironde
France CHU de Clermont-Ferrand Clermont-Ferrand Puy De Dôme
France CHU de Nantes Nantes Loire-Atlantique

Sponsors (1)

Lead Sponsor Collaborator
Nantes University Hospital

Country where clinical trial is conducted

France, 

Outcome

Type Measure Description Time frame Safety issue
Primary Safety of RLT using one injection of [177Lu]Lu-PentixaTher Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 Week 6
Primary Tolerance Tolerance of the RLT will be evaluated by dosimetry studies, especially in terms of renal and hepatic doses delivered Week 6
Secondary Overall response rate Response evaluation (CR, CRp and PR) after the infusion of [177Lu]Lu-PentixaTher Week 6
Secondary Complete response rate Response evaluation (CR, CRp) after the infusion of [177Lu]Lu-PentixaTher Week 6
Secondary Overall survival Time interval from the date from initial of study treatment (D0) until the date of last follow-up or death Month 12
Secondary Leukemia-free survival Time interval from the date of documented complete response (CR, CRp) until the date of last follow-up, death or relapse Month 12
Secondary Minimal residual disease CXCR4 expression by flow cytometry after [177Lu]Lu-PentixaTher Month 12
Secondary Whole-body biodistribution Serial whole body scintigraphies Week 6
Secondary Serum uptake The activity in each serum sample will be determined by counting 0,2 ml of serum in a calibrated gamma counter with an appropriate window setting. The maximal uptake (%) and area under the curve (AUC) of [ 177Lu]Lu-PentixaTher at the target lesion, organs and blood will be determined Week 6
Secondary Radiation dosimetry Whole body quantitative scintigraphies Week 6
Secondary Renal safety Renal safety will be assessed by measuring creatinine Month 12
Secondary Renal safety Renal safety will be assessed by measuring urea Month 12
Secondary Renal safety Renal safety will be assessed by measuring eGFR by MDRD or CKDEPI Month 12
Secondary Renal safety Renal safety will be assessed by measuring urinalysis Month 12
Secondary Correlation between different cytokines and toxicity FLT3 and IL6 serum level Month 12
Secondary Factors associated response Responses will be evaluated 4/6 weeks after the infusion of [177Lu]Lu-PentixaTher (Day 0): Complete remission (CR) is defined by normalization of the blood and the bone marrow with < or = 5% of blasts, neutrophil count > 1.109 /l and platelet count >100 Giga/l. CR with incomplete platelets recovery (CRp) is defined as for CR including platelet transfusion independence but with platelet count remaining below 100 Giga/l. Partial response (PR) is defined by blast clearance =50% in blood or bone marrow or bone marrow with > 5% and < 20 % of blasts Month 12
Secondary Exploratory outcome measure = Identification of biological biomarkers Different cytokines including FLT3 and IL6 serum levels will be monitored by serial blood sampling at D1, D8, D15, D22 as well as during the monitoring visits at 1 month, and only FLT3 and IL6 at 3, 6, 9 and 12 months Month 12
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