About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Signed informed consent, by the patient or an authorized legal guardian in case the patient is temporarily not competent due to his or her disease, obtained before any study-related activities. Study-related activities are any procedures that are carried out as part of the study, including activities to determine suitability for the study.

Patients of either gender aged > 18 years.

Body weight < 180 kg.

At least one measurable lymphoma manifestation in the CNS, either contrast-enhanced lesion in the brain parenchyma or measurable meningeal lesion.

Disqualifiers

Known or suspected hypersensitivity to study product(s) or related products.

Contraindication for contrast-enhanced magnetic resonance imaging (MRI) as set out in the relevant institutional guidelines (e.g., pacemaker, defibrillator, aneurysm clip, metal in the body, renal insufficiency, severe claustrophobia etc.) or contraindication for the use of gadolinium contrast for MRI.

Previous participation in this study. Participation is defined as signed informed consent.

Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate contraceptive method (adequate contraceptive measures as required by local regulation or practice). A pregnancy test will be performed at the start of the study for all female patients of childbearing potential (i.e., not surgically sterile or two years postmenopausal).

Trial design

Design model

Sequential

Treatments tested in this trial

[90Y]Y-PentixaTher
Drug
\[90Y\]Y-PTT i.v. injection

Treatment groups

15 Participants

are divided into 1 treatment group

Group A: [90Y]Y-PTTExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

Incidence, 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.

Secondary outcomes

1

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.

2

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.

3

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.

4

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.

Other outcomes

1

Incidence and severity of DLT

DLT (Dose limiting toxicity) is defined as a toxicity with a severity that prevents further increase in dose level. The incidence and the severity will be assessed.

Time frame

Up to 28 days post infusion

2

Changes from baseline in vital signs

Changes from the values of vital signs at screening visit will be assessed during the trial at different time points.

Time frame

Baseline: -28 to -8 days before infusion; End of infusion; 5 ± 2 / 30 ± 5 minutes post infusion (p.i) ; 1 hour ± 10 minutes p.i.; 5 ± 1 / 22 ± 4 hours p.i. ; 22 to 48 hours p.i.; 2 / 14 days p.i.; 1/ 3 / 6 / 9 / 12 months p.i.

3

Changes from baseline in laboratory parameters (hematology and biochemistry)

Changes from the values of laboratory parameters will be assessed during the trial at different time points.

Time frame

Hematology/Biochemistry: -28 to -8 days before infusion; Before infusion; 5 ± 1 hours post infusion (p.i.).; 2 days p.i.; 14 ± 2 days p.i; 1 / 3 months ± 5 days p.i.; 6 / 9 / 12 months ± 14 days p.i.;

4

Changes from baseline in laboratory parameters (urinalysis)

Changes from the values of laboratory parameters will be assessed during the trial at different time points.

Time frame

Urinalysis: -28 to -8 days before infusion; 0 to 5 hours post infusion (p.i.) (before 2nd scan); 5 to 22 hours p.i.(before 3rd scan); 22 to 48 hours p.i.(before 4th scan); 2 days p.i.; 14 ± 2 days p.i; 1 / 3 months ± 5 days p.i.;

[90Y]Y-PTT Endoradiotherapy in CNS Lymphoma Patients

About this trial

Eligibility criteria

Qualifiers

Disqualifiers

Trial design

Treatments tested in this trial

Treatment groups

Trial outcomes

Primary outcomes

Secondary outcomes

Other outcomes

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