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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

1. 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. 2. Patients of either gender aged > 18 years. 3. Body weight < 180 kg. 4. At least one measurable lymphoma manifestation in the CNS, either contrast-enhanced lesion in the brain parenchyma or measurable meningeal lesion. 5. Histologically confirmed diagnosis of relapsed or refractory primary central nervous system lymphoma (PCNSL) or histologically confirmed diagnosis of relapsed or refractory secondary central nervous system lymphoma (SCNSL) with only isolated CNS involvement (at initial diagnosis of relapse). 6. Recurrent or refractory CNSL. 1. For recurrent disease, comprising new lesions or recurrent CNSL after a complete response (CR) at that site, there are no maximum number of recurrences. 2. Refractory CNSL comprises patients with non-responding CNSL (no objective response rate (ORR), no progressive disease (PD)) to frontline therapy, or progressive disease after an initial, partial response (PR). 7. Stored stem cells with at least ≥ 2 x 106 CD34+ cells/kg of body weight. 8. 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. 9. Female patient without childbearing potential: documented history (e.g., tubal ligation or hysterectomy) or is post-menopausal. 10. 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. 11. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2. 12. 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. 13. Blood test results as follows: 1. Absolute neutrophil count: > 1.0 x 109/L. 2. Hemoglobin: ≥ 8 g/dL. 3. Platelets: ≥ 75 x 109/L. 4. Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase (ALP): ≤ 3 x ULN (upper limit of normal) 5. Serum creatinine: ≤ 2 x ULN and Cockcroft Gault calculated glomerular filtration rate (GFR) ≥ 50 mL/min. 6. Bilirubin: ≤ 3 x ULN.

Exclusion Criteria:

1. Known or suspected hypersensitivity to study product(s) or related products. 2. 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. 3. Previous participation in this study. Participation is defined as signed informed consent. 4. 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). 5. Male of reproductive age who or whose partner(s) is not using an adequate contraceptive method (adequate contraceptive measures as required by local regulation or practice). 6. Participation in any clinical study of an approved or non-approved investigational medicinal product (IMP) within the last 30 days (or ≤ 5 terminal elimination half-lives of previous IMP, whichever is longer) before screening. 7. Any disorder (e.g., active infection, unstable angina pectoris, cardiac arrhythmia (excluding atrial fibrillation and atrial flutter, uncontrolled congestive heart failure), poorly controlled hypertension, poorly controlled diabetes mellitus [HbA1c ≥ 9%], etc.) or laboratory findings, except for conditions associated with CNS lymphoma, which in the investigator's opinion might jeopardize patient's safety or compliance with the protocol. 8. Presence of active infection at screening, or history of serious infection within the previous six weeks. Patients with uncontrolled human immunodeficiency virus (HIV) infection as well as acute or chronic active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection are excluded (Note: Patients on antiretroviral therapy (ART) with controlled HIV infection (defined as sufficient ART compliance, non-measurable HIV and CD4+ T helper cells > 200/Micro Liter) may be enrolled, if considered eligible for study treatment by the investigator.). 9. SCNSL with systemic involvement. 10. Chronic use (> 21 days) of immunosuppressive drugs, e.g., steroids for systemic autoimmune disease, due to previous organ transplantation, or other clinically evident form of immunodeficiency. Patients receiving only acute treatment (less than 21 days) with corticosteroids can be included. 11. Any mental condition rendering the patient unable to understand the nature, scope, and possible consequences of the study, and/or evidence of an uncooperative attitude without designated legal representative.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT06132737
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1/Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Pentixapharm AG
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Bastian von Tresckow, Prof. Dr.
Principal Investigator Affiliation University Hospital, Essen
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Industry
Overall Status Recruiting
Countries Germany
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

CNS Lymphoma
Arms & Interventions

Arms

Experimental: [90Y]Y-PTT

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.

Interventions

Drug: - [90Y]Y-PentixaTher

[90Y]Y-PTT i.v. injection

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

International Sites

University Hospital Essen, Essen, Germany

Status

Recruiting

Address

University Hospital Essen

Essen, ,

Site Contact

Bastian von Tresckow, Prof. Dr.

PTT101@pentixapharm.com

+49-172-426-9635

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