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

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

NCT ID: NCT06356922

Condition: Acute Leukemia

Conditions: Official terms:
Leukemia
Acute Disease

Study type: Interventional

Study phase: Phase 1/Phase 2

Overall status: Not yet recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Experimental drug [177Lu]Lu-PentixaTher
Description: Injection of [177Lu]Lu-PentixaTher
Arm group label: [177Lu]Lu-PentixaTher

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.

Criteria for eligibility:
Criteria:
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

Gender: All

Minimum age: 18 Years

Maximum age: 100 Years

Healthy volunteers: No

Locations:

Facility:
Name: CHU de Bordeaux

Address:
City: Bordeaux
Zip: 33604
Country: France

Contact:
Last name: DUMAS Pierre-Yves

Contact backup:
Last name: pierre-yves.dumas@chu-bordeaux.fr

Facility:
Name: CHU de Nantes

Address:
City: Nantes
Zip: 44000
Country: France

Contact:
Last name: Patrice CHEVALLIER

Phone: 00332 40 08 39 94
Email: patrice.chevallier@chu-nantes.fr

Facility:
Name: CHU d'Angers

Address:
City: Angers
Zip: 49100
Country: France

Contact:
Last name: HUNAULT Mathilde
Email: mahunault@chu-angers.fr

Facility:
Name: CHU de Clermont-Ferrand

Address:
City: Clermont-Ferrand
Zip: 63000
Country: France

Contact:
Last name: MOLUCON Cécile
Email: cecile.chabrot@chu-clermontferrand.fr

Start date: September 15, 2024

Completion date: May 15, 2027

Lead sponsor:
Agency: Nantes University Hospital
Agency class: Other

Source: Nantes University Hospital

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06356922