Central Nervous system lymphoma Brain lymphoma Brain tumor
Conditions
Interventions
The study product is [68Ga]Ga-PentixaFor, otherwise referred to as PTF. It is a
positron emitter and is used in this study as a PET tracer. It will be
administered to each patient by bolus injection
Sponsors
PentixaPharm GmbH
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 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 =65 years;ECOG performance status
Exclusion criteria
Exclusion criteria: 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary efficacy endpoint will be the NPV of [68Ga]Ga-PentixaFor (PTF) PET at interim examination (after 6 ± 2 weeks of induction chemotherapy, PTF-PET2) for the prediction of 16 (±1) month PFS. | — |
Secondary
| Measure | Time frame |
|---|---|
| Major secondary efficacy endpoints will be the PPV of PTF PET at interim examination (PTF-PET2) for prediction of 16 (±1) month PFS; NPV and PPV of PTF-PET at end-of-chemotherapy (PTF PET3) for prediction of 16 (±1) month PFS; NPV and PPV of PTF-PET2 and PTF-PET3 for the prediction of complete response. Exploratory analyses of the association between PTF PET variables (standardised uptake value, tumour-to-background ratio, metabolic tumour volume) and PFS and CR will be performed. Sensitivity of PTF-PET to detect CXCR4 overexpression will be assessed. Agreement between PTF-PET and MRI concerning CNSL-suspicion will be determined, and inter- and intra-reader agreement will be checked. | — |
Countries
Netherlands
Outcome results
None listed