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

NCT06356922 | Recruiting Phase 1 DMC

• 1 other identifier: RC20_0123
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 4

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.

Conditions

Acute Leukemia

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (14)

• Overall response rate

  Between Week 4 and Week 6

• Complete response rate

  Between Week 4 and Week 6

• Overall survival

  Month 12

• Leukemia-free survival

  Month 12

• Minimal residual disease

  Month 12

Other Outcomes (1)

• Predictive role of PET/MRI (ancillary study)

  Between Week 4 and Week 6

Study Arms (1)

[177Lu]Lu-PentixaTher

EXPERIMENTAL

Injection of \[177Lu\]Lu-PentixaTher

Drug: Experimental drug [177Lu]Lu-PentixaTher

Interventions

Experimental drug [177Lu]Lu-PentixaTher DRUG

Injection of \[177Lu\]Lu-PentixaTher

[177Lu]Lu-PentixaTher

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• AML/ALL (OMS) with \>5% of blasts in bone marrow (with or without extramedullary localisation)
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Nantes University Hospital: lead

Study Sites (4)

CHU de Bordeaux

Bordeaux, Gironde, 33604, France

RECRUITING

CHU de Nantes

Nantes, Loire-Atlantique, 44000, France

RECRUITING

CHU d'Angers

Angers, Maine et Loire, 49100, France

RECRUITING

CHU de Clermont-Ferrand

Clermont-Ferrand, Puy de Dôme, 63000, France

RECRUITING

MeSH Terms

Interventions

Drugs, Investigational

Intervention Hierarchy (Ancestors)

Pharmaceutical Preparations

Central Study Contacts

Patrice CHEVALLIER

CONTACT

02 40 08 39 94; patrice.chevallier@chu-nantes.fr

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 22, 2024
• First Posted: April 10, 2024
• Study Start: October 22, 2024
• Primary Completion (Estimated): October 22, 2027
• Study Completion (Estimated): October 22, 2027
• Last Updated: April 16, 2026

Record last verified: 2026-04

Locations

FR (4)