- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06356922
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
Conditions
Intervention / Treatment
Study Type
Enrollment (Estimated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: Patrice CHEVALLIER
- Phone Number: 00332 40 08 39 94
- Email: patrice.chevallier@chu-nantes.fr
Study Locations
-
-
Gironde
-
Bordeaux, Gironde, France, 33604
- CHU de Bordeaux
-
Contact:
- DUMAS Pierre-Yves
-
Contact:
- pierre-yves.dumas@chu-bordeaux.fr
-
-
Loire-Atlantique
-
Nantes, Loire-Atlantique, France, 44000
- 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
- CHU d'Angers
-
Contact:
- HUNAULT Mathilde
- Email: mahunault@chu-angers.fr
-
-
Puy De Dôme
-
Clermont-Ferrand, Puy De Dôme, France, 63000
- 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
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: [177Lu]Lu-PentixaTher
Injection of [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
Time Frame: Week 6
|
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
|
Week 6
|
Tolerance
Time Frame: Week 6
|
Tolerance of the RLT will be evaluated by dosimetry studies, especially in terms of renal and hepatic doses delivered
|
Week 6
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall response rate
Time Frame: Week 6
|
Response evaluation (CR, CRp and PR) after the infusion of [177Lu]Lu-PentixaTher
|
Week 6
|
Complete response rate
Time Frame: Week 6
|
Response evaluation (CR, CRp) after the infusion of [177Lu]Lu-PentixaTher
|
Week 6
|
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
|
Month 12
|
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
|
Month 12
|
Minimal residual disease
Time Frame: Month 12
|
CXCR4 expression by flow cytometry after [177Lu]Lu-PentixaTher
|
Month 12
|
Whole-body biodistribution
Time Frame: Week 6
|
Serial whole body scintigraphies
|
Week 6
|
Radiation dosimetry
Time Frame: Week 6
|
Whole body quantitative scintigraphies
|
Week 6
|
Renal safety
Time Frame: Month 12
|
Renal safety will be assessed by measuring creatinine
|
Month 12
|
Renal safety
Time Frame: Month 12
|
Renal safety will be assessed by measuring urea
|
Month 12
|
Renal safety
Time Frame: Month 12
|
Renal safety will be assessed by measuring eGFR by MDRD or CKDEPI
|
Month 12
|
Renal safety
Time Frame: Month 12
|
Renal safety will be assessed by measuring urinalysis
|
Month 12
|
Correlation between different cytokines and toxicity
Time Frame: Month 12
|
FLT3 and IL6 serum level
|
Month 12
|
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
|
Month 12
|
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
|
Month 12
|
Serum uptake
Time Frame: Week 6
|
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
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- RC20_0123
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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