Study Assessing RLT Using [177Lu]Lu-PentixaTher for Relapsed/Refractory CXCR4+ Acute Leukemia. (PENTILULA)

Phase I/II Study Assessing Radioligand Therapy (RLT) Using [177Lu]Lu-PentixaTher for Relapsed/Refractory CXCR4+ Acute Leukemia.

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.

Study Overview

• Status: Recruiting
• Conditions: Acute Leukemia
• Intervention / Treatment: Drug: Experimental drug [177Lu]Lu-PentixaTher

• Study Type: Interventional
• Enrollment (Estimated): 21
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Patrice CHEVALLIER; Phone Number: +33 02 40 08 39 94; Email: patrice.chevallier@chu-nantes.fr

Study Locations

• France
  • Gironde
    • Bordeaux, Gironde, France, 33604
      • Recruiting
      • CHU de Bordeaux
      • Contact: DUMAS Pierre-Yves
      • Contact: pierre-yves.dumas@chu-bordeaux.fr
  • Loire-Atlantique
    • Nantes, Loire-Atlantique, France, 44000
      • Recruiting
      • CHU de Nantes
      • Contact: Patrice CHEVALLIER; Phone Number: 00332 40 08 39 94; Email: patrice.chevallier@chu-nantes.fr
  • Maine et Loire
    • Angers, Maine et Loire, France, 49100
      • Recruiting
      • CHU d'Angers
      • Contact: HUNAULT Mathilde; Email: mahunault@chu-angers.fr
  • Puy de Dôme
    • Clermont-Ferrand, Puy de Dôme, France, 63000
      • Recruiting
      • CHU de Clermont-Ferrand
      • Contact: MOLUCON Cécile; Email: cecile.chabrot@chu-clermontferrand.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: [177Lu]Lu-PentixaTher; Injection of [177Lu]Lu-PentixaTher	Drug: Experimental drug [177Lu]Lu-PentixaTher; Injection of [177Lu]Lu-PentixaTher

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of RLT using one injection of [177Lu]Lu-PentixaTher	Number of participants with treatment-related adverse events as assessed by CTCAE v5.0	Between Week 4 and Week 6
Tolerance	Tolerance of the RLT will be evaluated by dosimetry studies, especially in terms of renal and hepatic doses delivered	Between Week 4 and Week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Time interval from the date from initial of study treatment (D0) until the date of last follow-up or death	Month 12
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
Renal safety	Renal safety will be assessed by measuring creatinine	Month 12
Renal safety	Renal safety will be assessed by measuring urea	Month 12
Renal safety	Renal safety will be assessed by measuring eGFR by MDRD or CKDEPI	Month 12
Correlation between different cytokines and toxicity	FLT3 and IL6 serum level	Month 12
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
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
Overall response rate	Response evaluation (CR, CRp and PR) after the infusion of [177Lu]Lu-PentixaTher	Between Week 4 and Week 6
Complete response rate	Response evaluation (CR, CRp) after the infusion of [177Lu]Lu-PentixaTher	Between Week 4 and Week 6
Minimal residual disease	CXCR4 ratio by flow cytometry after [177Lu]Lu-PentixaTher	Month 12
Whole-body biodistribution	Serial whole body scintigraphies	Between Week 4 and Week 6
Plasma uptake	The activity in each plasma sample will be determined by counting 0,2 ml of plasma 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	Between Week 4 and Week 6
Radiation dosimetry	Whole body quantitative scintigraphies	Between Week 4 and Week 6

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Predictive role of PET/MRI (ancillary study)	SUVmax will be recorded in extra-medullary sites of pathological uptake.	Between Week 4 and Week 6

Collaborators and Investigators

• Sponsor: Nantes University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 22, 2024
• Primary Completion (Estimated): October 22, 2027
• Study Completion (Estimated): October 22, 2027

Study Registration Dates

• First Submitted: March 22, 2024
• First Submitted That Met QC Criteria: April 9, 2024
• First Posted (Actual): April 10, 2024

Study Record Updates

• Last Update Posted (Actual): April 16, 2026
• Last Update Submitted That Met QC Criteria: April 13, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease Attributes; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia; Acute Disease; Pharmaceutical Preparations; Drugs, Investigational
• Other Study ID Numbers: RC20_0123

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No