This will be an open-label, single-arm, national phase 1/2 therapeutic study to evaluate the safety, tolerability, and preliminary efficacy of \[90Y\]Y-PentixaTher (\[90Y\]Y-PTT) for the treatment of recurrent or refractory primary or isolated secondary central nervous system (CNS) lymphoma. The study will be performed in three cohorts with different dose levels according to the best-of-5 dose escalation design. A safety review committee (SRC) will evaluate dose-limiting toxicities and decide about escalation and de-escalation. Eligible patients will receive one cycle of \[90Y\]Y-PTT, which will be administered intravenously. There will be no comparator in this study. Safety, biodistribution, dosimetry and efficacy will be evaluated during the core study phase (Visit 1 until Visit 5). Thereafter three follow-up (FU) visits will take place, at three-months intervals to evaluate the extent of disease.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
15
\[90Y\]Y-PTT i.v. injection
University Hospital Rechts der Isar
Munich, Bavaria, Germany
WITHDRAWNUniversity Hospital Essen
Essen, Germany
RECRUITINGIncidence, severity and relationship of (S)AEs (graded in severity according to NCI CTCAE version 5.0)
Incidence, severity and relationship of (/serious) adverse events (S)AEs will be analyzed by descriptive statistical methods. The analyses will be based on the safety analysis set (SAF). AEs as well as SAEs will be tabulated. Verbatim terms will be coded using the Medical Dictionary for Regulatory Activities (MedDRA), and tabulations will occur by System Organ Class and Preferred Term. Severity will be graded and tabulated according to NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Treatment-emergent AEs will be the focus of the analyses. AEs and SAEs assessed as causality related to IMP by the investigator, and AEs leading to death will be tabulated separately.
Time frame: From screening until including the last follow-up visit. SAEs occuring after the end of the study should only be reported to Pentixapharm if the Investigator considers there is a causal relationship with the study drug.
Maximal uptake (%) for tumor lesion
The lesion activity values will be determined manually. Two volume of interests (VOIs) are drawn around a slightly enlarged organ/lesion contour, based on the computed tomography (CT) and a sphere centered around the maximal activity.
Time frame: 1 ± 0.5 hours post infusion (p.i.).; 5 ± 1 hours p.i.; 22 ± 4 hours p.i.; 30 ± 4 hours p.i.
Maximal uptake (%) in discernible organs
The organ activity values will be determined manually. Two volume of interests (VOIs) are drawn around a slightly enlarged organ/lesion contour, based on the CT and a sphere centered around the maximal activity.
Time frame: 1 ± 0.5 hours post infusion (p.i.); 5 ± 1 hours p.i.; 22 ± 4 hours p.i.; 30 ± 4 hours p.i.
TAC in discernible thoracic and abdominal organs, target lesion and blood
The organ/lesion activity values will be determined manually. Two volume of interests (VOIs) are drawn around a slightly enlarged organ/lesion contour, based on the CT and a sphere centered around the maximal activity. For both evaluations the total activity will be noted and scaled to the injected activity. The Time activity curves (TAC) will be calculated. The blood samples will be measured in a calibrated well counter. Applying the calibration factor, the counts will be converted to activity of the blood samples.
Time frame: Discernible thoracic /abdominal organs /target lesion: 1 ± 0.5 hours post infusion (p.i.).; 5 ± 1 hours p.i.; 22 ± 4 hours p.i.; 30 ± 4 hours p.i. For Blood: 5 ± 2 minutes, 30 ± 5 minutes, 1 hour ± 10 minutes, 5 ± 1 hours, 22 ± 4 hours, 48 ± 6 hours p.i.
AUC of 90Y-PTT in discernible thoracic and abdominal organs, target lesion and blood
The organ/lesion activity values will be determined manually. Two volume of interests (VOIs) are drawn around a slightly enlarged organ/lesion contour, based on the CT and a sphere centered around the maximal activity. For both evaluations the total activity will be noted and scaled to the injected activity. The time activity curves (TAC) will be calculated. The blood samples will be measured in a calibrated well counter. Applying the calibration factor, the counts will be converted to activity of the blood samples. The area under the curve (AUC) will be calculated.
Time frame: Discernible thoracic /abdominal organs /target lesion: 1 ± 0.5 hours post infusion (p.i.).; 5 ± 1 hours p.i.; 22 ± 4 hours p.i.; 30 ± 4 hours p.i. For blood: 5 ± 2 minutes, 30 ± 5 minutes, 1 hour ± 10 minutes, 5 ± 1 hours, 22 ± 4 hours, 48 ± 6 hours p.i.
AUC of 90Y-PTT in urine
The activity concentrations of the collected urine will be measured in a well counter. The area under the curve (AUC) will be calculated.
Time frame: 0 - 5 hours (before 2nd PET scan); 5 - 22 hours (before 3rd PET scan); 22 - 48 hours
Organ receiving the highest absorbed dose
The organ/lesion activity values will be determined manually. Two volume of interests (VOIs) are drawn around a slightly enlarged organ/lesion contour, based on the computed tomography (CT) and a sphere centered around the maximal activity.
Time frame: 1 ± 0.5 hours post infusion (p.i).; 5 ± 1 hours p.i.; 22 ± 4 hours p.i.; 30 ± 4 hours p.i.
Cumulative absorbed organ/lesion doses (Gy)
The organ/lesion activity values will be determined manually. Two volume of interests (VOIs) are drawn around a slightly enlarged organ/lesion contour, based on the CT and a sphere centered around the maximal activity.
Time frame: 1 ± 0.5 hours post infusion (p.i).; 5 ± 1 hours p.i.; 22 ± 4 hours p.i.; 30 ± 4 hours p.i.
ORR at one month and three months
Proportion of patients who have partial response or complete response after treatment during study duration according to (International Primary Central Nervous System Lymphoma Collaborative Group) IPCG response criteria. This is also called the objective response rate (ORR).
Time frame: Month 1 (Visit 4) and Month 3 (Visit 5)
PFS at one month and three months
Proportion of patients whose status results in death or progressive disease or disease relapse after achieving complete response according to IPCG response criteria. This is also called progression-free survival (PFS).
Time frame: Month 1 (Visit 4) and Month 3 (Visit 5) post infusion
Rate of CR and PR at one month and three months
Proportion of patients with complete response (CR) and partial response (PR) according to IPCG response criteria.
Time frame: Month 1 (Visit 4) and Month 3 (Visit 5) post infusion
PFS at 12 month (including a nine-month FU according to the local investigator's discretion)
Progression free survival (PFS) of patients according to IPCG response criteria.
Time frame: 6 months post infusion (p.i.); 9 months p.i.; 12 months p.i.;
OS at 12 month (including a nine-month FU according to the local investigator's discretion)
Overall survival (OS) at 6 months, 9 months and 12 months after infusion is assessed.
Time frame: 6 months post infusion (p.i.); 9 months p.i.; 12 months p.i.;
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