Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| [90Y]Y-PTT | Experimental | The study will be performed in three cohorts with different dose levels. Eligible patients will receive one cycle of 90Y-PTT, which will be administered intravenously. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| [90Y]Y-PentixaTher | Drug | [90Y]Y-PTT i.v. injection |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 1 ± 0.5 hours post infusion (p.i.).; 5 ± 1 hours p.i.; 22 ± 4 hours p.i.; 30 ± 4 hours p.i. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Up to 28 days post infusion |
| Changes from baseline in vital signs |
Inclusion Criteria:
Patients are eligible to be included in the study only if all of the following criteria apply and are maintained at Day -2 to Day 0 (before IMP infusion):
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.
Histologically, cytologically or radiologically confirmed relapsed/refractory primary central nervous system lymphoma (PCNSL) or relapsed/refractory secondary central nervous system lymphoma (SCNSL). Initial histologic confirmation at first diagnosis is mandatory. No peripheral lymphoma evidence is allowed.
Recurrent or refractory CNSL
Stored stem cells with at least ≥ 2 x 106 CD34+ cells/kg of body weight.
If sexually active female patient of childbearing potential: patient agrees to take adequate contraceptive measures during study participation and agrees to continue use of this method for the duration of the study and for six months after the last dose.
Female patient without childbearing potential: documented history (e.g., tubal ligation or hysterectomy) or is post-menopausal.
For male patient whose partner is of child-bearing potential: patient is willing to ensure that he and his partner use effective contraception during the study and for six months after 90Y-PTT treatment.
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
Confirmed presence of CXCR4 on technically evaluable tumor lesions documented by a visually CXCR4-positive [68Ga]Ga-PentixaFor positron emission tomography (PET) scan within two months prior to enrolment in the study or during Screening.
Blood test results as follows:
Exclusion Criteria:
Patients are excluded from the study if any of the following criteria apply during screening or Day -2 to Day 0 (before IMP infusion):
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Simone Pickel | Contact | +49-172-426-9635 | PTT101@pentixapharm.com |
| Name | Affiliation | Role |
|---|---|---|
| Bastian von Tresckow, Prof. Dr. med. | University Hospital, Essen | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospital Rechts der Isar | Withdrawn | Munich | Bavaria | 81675 | Germany | |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| 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. | 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. | 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. | 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. | 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. | 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. | 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). | 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). | 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. | 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. | 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. | 6 months post infusion (p.i.); 9 months p.i.; 12 months p.i.; |
Changes from the values of vital signs at screening visit will be assessed during the trial at different time points. |
| 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. |
| 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. | 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.; |
| Changes from baseline in laboratory parameters (urinalysis) | Changes from the values of laboratory parameters will be assessed during the trial at different time points. | 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.; |
| Abnormal findings in physical examination | Changes from values of the physical examination will be assessed during the trial at different time points. | -28 to -8 days before infusion; Before infusion; 2 days post infusion (p.i.); 14 ± 2 days p.i; 1 / 3 months ± 5 days p.i.; 6 / 9 / 12 months ± 14 days p.i.; |
| Findings12-lead ECG | Changes from values of the 12-lead electrocardiogram (ECG) will be assessed during the trial at different time points. | -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. |
| University Hospital Essen |
| Recruiting |
| Essen |
| Germany |
|