Metastatic melanoma
Conditions
Interventions
Group 1: Single-dose MB-CART20.1, intravenous
Sponsors
Miltenyi Biomedicine GmbH
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Histologically confirmed unresectable stage III or stage IV melanoma 2. Willingness to provide a tumor biopsy between the screening visit and prior to administration of the IMP and eight weeks after treatment 3. Progressive disease despite treatment with indicated standard therapies. Time window for decision about progressive disease is to be made depending on the treatment regimen chosen. 4. Measurable lesions according to RECIST1.1 5. ECOG (Eastern cooperative oncology group) performance status of 0-2 6. Negative serological hepatitis B (HBV) test defined as negative tests for HBsAg and HBcAb, unless serology is positive due to recent IVIG therapy, HBcAb positivity will be allowed if HbsAb is present, negative testing of HCVAb, negative human immunodeficiency virus (HIV) 1/2 test within 6 weeks prior to enrollment. 7. Estimated life expectancy of more than 6 months 8. At least 18 years of age 9. WBC = 2500/µL 10. ANC = 1000/µL 11. Platelets = 75 x 103/µL 12. Hemoglobin = 9 g/dL 13. AST = 3 x upper limit of normal (ULN) for patients without liver metastasis 14. AST < 5 x ULN for patients with liver metastasis 15. Total Bilirubin = 2 x ULN 16. patients with Gilbert’s Syndrome increase of indirect bilirubin < 6mg/dL 17. No childbearing potential (i.e. postmenopausal, absence of menstrual bleeding for at least 1 year, hysterectomy, bilateral ovariectomy or tubal section/ligation) or negative pregnancy test at screening and before chemotherapy in women with childbearing potential. Sexually active female patients of childbearing potential should use one of the following highly effective methods of contraception (Pearl index < 1%): hormonal contraceptives (oral, injected, implanted, transdermal), intrauterine devices or systems (e.g. hormonal and non-hormonal IUD), or vasectomized sexual partner for at least 1 month before the trial start, during the course of the trial and in the 6 months following dosing. Sexual abstinence is restricted to true abstinence ( in line with the preferred and usual lifestyle of the subject). 18. male patients, unless surgically sterile, must be using two acceptable methods for contraception (e.g. spermicide and condom) during the trial and refrain from fathering a child throughout the trial and for up to 12 months after dosing. 19. Signed and dated informed consent before conduct of any trial-specific procedure.
Exclusion criteria
Exclusion criteria: 1. Any evidence of brain metastases 2. Known history or presence of clinically relevant central nervous System (CNS) pathology, such as epilepsy, paresis, aphasia, stroke within the Prior 3 months, severe brain injuries, Dementia, Parkinson’s disease, cerebellar disease, organic brain syndrome, uncontrolled mental illness or psychosis. Patients with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the CNS 3. Patients with any history of clinically relevant auto-immune induced condition such as those caused by checkpoint inhibitors must be excluded 4. Clinically relevant autoimmune disorders or history of clinically relevant autoimmune disorders 5. Patients with T-cell lymphoma 6. Treatment with anti-CD20 antibodies, checkpoint blockade Inhibitors or targeted agents (kinase inhibitors e.g. BRAF/MEK) within 4 weeks before leukapheresis 7. Chemotherapy within 4 weeks prior to leukapheresis 8. History of primary immunodeficiency 9. 9. GFR < 30 ml/min calculated according to CKD-Epi formula. 10. concurrent systemic radiotherapy 11. Use of systemic corticosteroids and immunosuppressive medication except prednisone = 10 mg QD or equivalent 12. Patients with severe cardiac disease (e.g. NYHA Functional Class III or IV, myocardial infarction within 6 months before inclusion, ventricular tachyarrhythmia requiring ongoing treatment, unstable angina pectoris) 13. Other investigational treatment within 2 weeks before leukapheresis 14. Hypersensitivity against any drug or its ingredients/impurities that is scheduled or likely to be given during trial participation, e.g. as part of the mandatory lymphodepletion protocol, pre-medication for infusion, rescue medication/salvage therapies for treatment related toxicities 15. Patients in which such medication (likely to be given during trial participation) is contraindicated for other reasons than hypersensitivity, e.g. live vaccines and fludarabine. 16. Severe pulmonary disease (DLCO and/or FEV1 < 65%, dyspnoea at rest) 17. Active systemic fungal, viral or bacterial infection 18. Pregnant or lactating women 19. Patient’s lack of accountability, inability to appreciate the nature, meaning and consequence of the trial and to formulate his/her own wishes correspondingly 20. Patients who have a relationship of dependence or employer employee relationship to the sponsor or the investigator 21. Committal to an institution on judicial or official order
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Determination of the maximum tolerated dose (MTD), defined as the highest dose level at which < 33% of patients experience dose limiting toxicity (DLT) until week 4 after infusion of MB-CART20.1. Safety and toxicity assessment of MB-CART20.1 per adverse events (AE) reporting classified according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. | — |
Secondary
| Measure | Time frame |
|---|---|
| Clinical response: Number and percentage of patients with Complete Response; Partial Response; Stable Disease; Progressive Disease; Frequency and duration of B-cell aplasia; Phenotype and Persistence of infused MB-CART20.1; Presence and phenotype of MB-CART20.1 and B cells in biopsies; Number of CD20+ tumor cells Persistence of T-cell expansion for each dose group | — |
Countries
Germany
Contacts
Public ContactPeter Borchmann
Universitätsklinikum Köln
Outcome results
None listed