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

Acute Leukemia Clinical Trial

— PENTILULA  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06356922
• Other study ID #: RC20_0123
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• 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
• 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

Related Conditions & MeSH terms

• Acute Disease
• Acute Leukemia
• Leukemia

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