eurological adverse events in tumor patients receiving CAR-T-cells and immune checkpoint inhibitors: clinical and molecular patterns of toxicityeffects

• Conditions: Tumor patients with B-cell lymphomas, leukemias, NSCLC, metastatic melanoma, or urologic tumors who are receiving system therapy with or without immunotherapy; C00-C14; C34; C43-C44; C64-C68; Malignant neoplasms of lip, oral cavity and pharynx; Malignant neoplasm of bronchus and lung; Melanoma and other malignant neoplasms of skin; Malignant neoplasms of urinary tract

• Registration Number: DRKS00032520
• Lead Sponsor: niversitätsklinikum Jena

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2023-08-18
• Last Update Posted: 19 August 2024

Recruitment & Eligibility

• Status: Pending
• Sex: All
• Target Recruitment: 220

Inclusion Criteria

Inclusion criteria ICI cohort:
- Age = 18 years, female or male sex.
- Capacity to consent given or legal guardian available
- Informed consent available
- Histologically confirmed bronchial carcinoma (NSCLC), metastasized
melanoma or urological tumor
- Therapy regime with immune checkpoint inhibition indicated &.
Treatment planned at UKJ
- ECOG status 0-2 / Karnofsky index > 50 %***
- MRI suitability given
- No known gadolinium intolerance/contraindication
- No intake of steroids > 3 mg dexamethasone or
Equivalent at the time of study enrollment

Inclusion criteria CAR T-cell cohort:
- Age = 18 years, female or male sex.
- Capacity to give consent given or legal guardian available
- Informed consent available
- histologically confirmed hematological neoplasia, depending on the preparation
with approved indication for treatment with CAR-T at the time of individual recruitment
indication for treatment with CAR-T cells in Germany (e.g.
B-cell lymphoma, leukemias)
- Therapy with CAR-T cells in the hematooncological tumor board
indicated & treatment planned at UKJ
- ECOG status 0-2 / Karnofsky index > 50 %***
- MRI suitability given
- No known gadolinium intolerance/contraindication
- No use of steroids at the time of study enrollment
(> 3 mg dexamethasone or equivalent)

Inclusion criteria physician's choice cohort:
(PARTICIPATE control group):
- Age = 18 years, female or male sex.
2023_06_13 Version 1.3_PARTICIPATE Protocol Page 12 of 65
- Capacity to consent given or legal guardian present.
- Informed consent available
- Histologically confirmed hematological neoplasia (if possible
matched pairs strategy with respect to line of therapy and entity of the
CAR T-cell target cohort), bronchial carcinoma, metastatic melanoma
melanoma or urological tumor
- Systemic treatment planned at UKJ
- Oncologic systemic treatment (except immunotherapies!) indicated & planned at the UKJ
- No preceding or parallel planned ICI therapy
- ECOG status 0-2 /Karnofsky index > 50 %***
- MRI suitability given
- No known gadolinium intolerance/contraindication
- No use of steroids > 3 mg dexamethasone or equivalent

Exclusion Criteria

- No Informed Consent available
- Simultaneous participation in an interventional clinical trial
trial
- Presence of further tumor diseases requiring treatment
(incl. exclusive need for radiotherapy or surgery),
other than systemically treated entity; except for
treated prostate carcinoma with PSA < 0.2 ng/ml as well as non-invasive
dermatologic tumors (basal cell carcinomas /
squamous cell carcinomas)
- Presence of a persistent neurological disorder CTCAE grade 4
or persistent pre-therapy associated neurotoxicity grade
4 at the time of therapy initiation
- MRI suitability not given, e.g. in case of
a. pronounced obesity with BMI >30 kg/m²
b. Condition after pacemaker fitting
c. non-MR compatible implants, e.g. port system
- known gadolinium intolerance/contraindication
- Relevant drug immunosuppression prior to initiation of
Immune checkpoint inhibition (incl. > 3 mg dexamethasone or
equivalent)
- Other known immunosuppression (e.g., as congenital
immunodeficiency syndrome)
- Pregnancy or lactation
- Presence of a contagious infectious disease
(especially HIV, hepatitis B or C) at the time of study enrollment

Study & Design

• Study Type: observational
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The primary objective of the study is to characterize morphological abnormalities associated with immunotherapy-induced neurological symptoms during immunotherapy. Patients will be examined prior to therapy and at 6 time points during the 12 months of systemic treatment (baseline, 7-14 days, 6 weeks, 3 months, 6 months, 12 months after study inclusion) using the multimodal diagnostic concept of the study (observation phase). Subsequently, a one-time follow-up is carried out after 6 months on the basis of the patient files for the final documentation of the oncological course and neurological outcome. <br><br>Primary outcome:<br>• Presence of morphological changes in patients with immunotherapy-associated neurological deterioration at the time of onset and within 12 months after the start of immunotherapy<br>- Change in NANO / EDSS / TNS and MRI category / sonography score<br>- Change in MMST / ICE / MOCA and MRI category