Central nervous system (CNS) lymphoma MedDRA version: 21.1 Level: PT Classification code 10028997 Term: Neoplasm malignant System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
PentixaPharm GmbH
Eligibility
Sex/Gender
All
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 = 2 for patients aged =65 years;ECOG performance status = 3 for patients aged =65 years) yes F.1.3.1 Number of subjects for this age range 15
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) 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the negative predictive value (NPV) of [68Ga]Ga-PentixaFor (PTF)-PET at interim examination (after 6 ± 2 weeks of induction chemotherapy) for progression-free survival (PFS).;Secondary Objective: TO EVALUATE : the positive predictive value of PTF-PET at interim examination for PFS, and the safety and tolerability of PTF-PET imaging,and the predictive values of PTF-PET at the end of induction chemotherapy for PFS, and the predictive values of PTF-PET at interim examination and end-of-chemotherapy-treatment for complete response(CR), and the predictive values of pre-treatment PTF-PET imaging parameters for PFS and CR, and the predictive values of interim PTF-PET imaging parameters for PFS and CR, and the predictive values of changes between pretreatment and interim PTF-PET imaging parameters for PFS. To determine the sensitivity of pre-treatment PTF-PET for CXCR4-positivity in the fraction of patients from whom biopsy tissue is available, by using histopathology as the reference standard on a patient basis. TO EVALUATE: the diagnostic agreement between PTF-PET and MRI at baseline imaging on a patient level, and the observer agreement of PTF PET;Primary end point(s): 1. to evaluate the negative predictive value (NPV) of [68Ga]Ga-PentixaFor (PTF) PET at interim examination (after 6 ± 2 weeks of induction chemotherapy) for progression-free survival (PFS).;Timepoint(s) of evaluation of this end point: Patients will be evaluated after 6 weeks of induction Chemotherapy | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 2. To evaluate the positive predictive value (PPV) of PTF PET at interim examination (after 6 ± 2 weeks of induction chemotherapy) for PFS. 3.To evaluate the safety and tolerability of PTF PET imaging. 4.To evaluate the predictive values of PTF PET at the end of induction chemotherapy for PFS. 5.To evaluate the predictive values of PTF PET at interim examination (after 6 ± 2 weeks of induction chemotherapy) and end-of-chemotherapy-treatment for complete response (CR). 6.To evaluate the predictive values of pre-treatment PTF PET imaging parameters for PFS and CR. 7.To evaluate the predictive values of interim (after 6 ± 2 weeks of induction chemotherapy) PTF PET imaging parameters for PFS and CR. 8.To evaluate the predictive values of changes between pre-treatment and interim (after 6 ± 2 weeks of induction chemotherapy) PTF PET imaging parameters for PFS. 9.To determine the sensitivity of pre-treatment PTF PET for CXCR4-positivity in the fraction of patients from whom biopsy tissue is available, by using histopathology (CXCR4 overexpression by immunohistochemistry, IHC) as the reference standard on a patient basis. 10.To evaluate the diagnostic agreement between PTF PET and MRI at baseline imaging on a patient level. 11.To evaluate the observer agreement of PTF PET (inter- and intra-reader agreement). ;Timepoint(s) of evaluation of this end point: Patients will be evaluated after 6 ± 2 weeks of induction chemotherapy for PFS and after 6 ± 2 weeks of induction chemotherapy and end-of-chemotherapy-treatment for complete response (CR). | — |
Countries
Denmark, France, Germany, Italy, Netherlands, United States
Contacts
Public ContactSenior Clinical Research Manager
PentixaPharm GmbH
Outcome results
None listed