Skip to main content
OpenTrials
Recruiting

NCT Number: NCT06356922

Study Assessing 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.

Recruiting

Interested in participating?

Request Info

Key information

Conditions

Acute Leukemia

Age range

18 year–100 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

CHU de Bordeaux, Bordeaux, Gironde, France

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Experimental drug [177Lu]Lu-PentixaTher

Drug

Injection of [177Lu]Lu-PentixaTher

Primary outcomes

  1. Safety of RLT using one injection of [177Lu]Lu-PentixaTher

    Time frame: Between Week 4 and Week 6

    Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

  2. Tolerance

    Time frame: Between Week 4 and Week 6

    Tolerance of the RLT will be evaluated by dosimetry studies, especially in terms of renal and hepatic doses delivered

Secondary outcomes

  1. Overall response rate

    Time frame: Between Week 4 and Week 6

    Response evaluation (CR, CRp and PR) after the infusion of [177Lu]Lu-PentixaTher

  2. Complete response rate

    Time frame: Between Week 4 and Week 6

    Response evaluation (CR, CRp) after the infusion of [177Lu]Lu-PentixaTher

  3. Overall survival

    Time frame: Month 12

    Time interval from the date from initial of study treatment (D0) until the date of last follow-up or death

  4. Leukemia-free survival

    Time frame: Month 12

    Time interval from the date of documented complete response (CR, CRp) until the date of last follow-up, death or relapse

  5. Minimal residual disease

    Time frame: Month 12

    CXCR4 ratio by flow cytometry after [177Lu]Lu-PentixaTher

  6. Whole-body biodistribution

    Time frame: Between Week 4 and Week 6

    Serial whole body scintigraphies

  7. Plasma uptake

    Time frame: Between Week 4 and Week 6

    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

  8. Radiation dosimetry

    Time frame: Between Week 4 and Week 6

    Whole body quantitative scintigraphies

  9. Renal safety

    Time frame: Month 12

    Renal safety will be assessed by measuring creatinine

  10. Renal safety

    Time frame: Month 12

    Renal safety will be assessed by measuring urea

  11. Renal safety

    Time frame: Month 12

    Renal safety will be assessed by measuring eGFR by MDRD or CKDEPI

  12. Correlation between different cytokines and toxicity

    Time frame: Month 12

    FLT3 and IL6 serum level

  13. Factors associated response

    Time frame: Month 12

    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

  14. Exploratory outcome measure = Identification of biological biomarkers

    Time frame: Month 12

    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

Other outcomes

  1. Predictive role of PET/MRI (ancillary study)

    Time frame: Between Week 4 and Week 6

    SUVmax will be recorded in extra-medullary sites of pathological uptake.

Study contacts

Contact information is provided by the study sponsor or research team.

Patrice CHEVALLIER

CONTACT

[email protected]

02 40 08 39 94 ext. +33

Sponsors and collaborators

Lead sponsor

Nantes University Hospital

Other

Registry information

Official study title

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

Acronym: PENTILULA

Important dates

Study start
2024
Primary completion
2027
Study completion
2027
First posted
Apr 10, 2024
Registry last updated
Apr 16, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.