A prospective, international, multi-centre, open-label,single-arm phase II study investigating the predictive value of [68Ga]Ga-PentixaFor PET imaging in primary and isolated secondary CNS lymphoma patients
- Conditions
- Central Nervous system lymphomaBrain lymphomaBrain tumor10025322
- Registration Number
- NL-OMON51764
- Lead Sponsor
- PentixaPharm GmbH
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Withdrawn
- Sex
- Not specified
- Target Recruitment
- 6
All study patients must meet all the following criteria:
1.Written informed consent obtained according to international guidelines and
local laws by patient (or legally acceptable representative if the patient is
temporarily legally not competent owing to his/her disease). [Note: No invasive
study-specific procedures may be carried out until this consent has been given.]
2.Patient aged 18 years or above (either sex).
3.Histologically confirmed primary or secondary CNSL based on cytology/flow
cytometry of cerebrospinal fluid (CSF) or brain biopsy.
4.Disease exclusively located in the CNS (primary CNSL or secondary CNSL with
isolated CNS relapse). Subjects who had undergone allogeneic stem cell
transplant > 12 months prior to first dose of study drug, have no evidence
of active graft versus host disease, and are not on systemic immunosuppressive
therapy are allowed to participate in the study.
5.At least one measurable parenchymal lesion. [Note: parenchymal CNSL is a
*must*, and additional locations such as leptomeningeal disease are permitted.]
6.Previously untreated CNS disease.[Note: Previous or ongoing steroid treatment
is permitted. Prophylaxis chemotherapy is not necessary, as induction
chemotherapy will start within 72 hours after PTF-PET.]
7.At least one morphologically measurable lesion according to the IPCG criteria
(Appendix 1).
8.Patients scheduled to undergo induction chemotherapy based on one of the
following: High-dose methotrexate (HD-MTX)-based chemotherapy, ICE/DeVIC or
High-dose cytarabine (HD-AraC)-based chemotherapy.
9.ECOG performance status <= 2 for patients aged >=65 years;ECOG performance
status <= 3 for patients aged <65 years.
10.Life expectancy of at least 3 months, as estimated by the investigator.
11.For women of child-bearing potential: negative pregnancy test.
12.For sexually active female patients of child-bearing potential: The patient
agrees to take adequate contraceptive measures during study participation and
also agrees to continue use of this method for the duration of the study and
for 6 months after the last dose of PTF.
13.For male patients whose partner is of child-bearing potential: The patient
is willing to ensure that he and his partner use effective contraception during
the study and for 6 months after the last dose of PTF.
Any patient meeting one or more of the following criteria will not be included:
1.Known hypersensitivity to [68Ga]Ga-PentixaFor or its components.
2.Contraindication for contrast-enhanced MRI as set out in the relevant
institutional guidelines (e.g., pacemaker, defibrillator, aneurysm clip, metal
in the body, renal insufficiency, severe claustrophobia etc.).
3.Contraindication for the use of gadolinium contrast for MRI.
4.Contraindication for PET according to institutional guidelines (weight-based,
e.g. weight > 180 kg).
5.Inability to lie still for the entire imaging time.
6.Systemic lymphoma manifestation (outside the CNS).
7.Presence of active infection at screening or history of serious infection
within the previous 6 weeks (except HIV infection: patients with HIV-associated
primary CNSL are considered eligible).
8.Administration of another investigational medicinal product within the 30
days (or 5 excretion half-lives, whichever period is the longer) before first
treatment with PTF.
[Note: Re screening may be performed to accept washout of prior agents.]
9.Current toxicity of Grade >2 from previous standard or investigational
therapies (grade according to the NCI Common Terminology Criteria for Adverse
Events, version 5.0 (CTCAE 5.0).
10.For female patients: Pregnancy (existing or intended) or breast-feeding.
11.Renal impairment: Both of the following: Estimated glomerular filtration
rate (eGFR) < 30 ml/min/1.73 m2 Creatinine clearance < 60 ml/min
12.Hepatic impairment: Both of the following: Aspartate aminotransferase (AST)
> 3 upper limit of normalAlanine aminotransferase (ALT) > 3 upper limit
of normal
13.Presence of any unstable systemic disease (including, but not limited to,
active infection, uncontrolled hypertension, unstable angina, congestive heart
failure, serious cardiac arrhythmia requiring medication, hepatic, renal or
metabolic disease.
14.Presence of psychiatric disease, alcohol abuse or any other medical
condition(s) that, in the opinion of the investigator, makes the patient unable
to comply with study procedures and visits.
15. Patient weight <= 48 kg
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary efficacy endpoint will be the NPV of [68Ga]Ga-PentixaFor (PTF) PET<br /><br>at interim examination (after 6 ± 2 weeks of induction chemotherapy, PTF-PET2)<br /><br>for the prediction of 16 (±1) month PFS.</p><br>
- Secondary Outcome Measures
Name Time Method <p>Major secondary efficacy endpoints will be the PPV of PTF PET at interim<br /><br>examination (PTF-PET2) for prediction of 16 (±1) month PFS; NPV and PPV of<br /><br>PTF-PET at end-of-chemotherapy (PTF PET3) for prediction of 16 (±1) month PFS;<br /><br>NPV and PPV of PTF-PET2 and PTF-PET3 for the prediction of complete response.<br /><br>Exploratory analyses of the association between PTF PET variables (standardised<br /><br>uptake value, tumour-to-background ratio, metabolic tumour volume) and PFS and<br /><br>CR will be performed. Sensitivity of PTF-PET to detect CXCR4 overexpression<br /><br>will be assessed. Agreement between PTF-PET and MRI concerning CNSL-suspicion<br /><br>will be determined, and inter- and intra-reader agreement will be checked.</p><br>