Golcadomide for Secondary central nervous system lymphoma|Relapsed primary central nervous system large B-cell lymphoma|Refractory primary central nervous system large B-cell lymphoma

Inclusion criteria

• {"criterion_text":"- ≥ 18 years as minimum age\n- Additional inclusion criteria cohort A: Patients must have received prior high-dose methotrexate based chemotherapy.\n- Additional inclusion criteria cohort B: Diagnosis of aggressive malignant B-cell lymphoma based upon a representative histology specimen according to the WHO 2022 classification: Follicular lymphoma (FL) grade 3B or transformed FL, DLBCL and HGBCL with MYC and BCL2 rearrangements\n- Additional inclusion criteria cohort B: Progression or relapse with CNS localization with or without systemic relapse\n- Additional inclusion criteria cohort B: 3\tDiagnosis of CNS localization at inclusion based on at least one of the following: Unequivocal morphological and/or immunophenotypically evidence of Cerebrospinal Fluid (CSF) lymphoma, clinical AND Magnetic resonance imaging (MRI) evidence of leptomeningeal localization, brain parenchymal lesion showing homogeneous contrast enhancement suspect for lymphoma, concurrently with systemic progression or recurrence and biopsy-proven brain parenchymal NHL localization of previously diagnosed systemic NHL\n- WHO-performancestatus ≤ 2\n- Patient must understand and voluntarily sign an Informed Concent Form (ICF) prior to any study related assessments/procedures being conducted\n- Patient is willing and able to adhere to the study visit schedule and other protocol requirements\n- Haemoglobin > 5 mmol/l\n- Absolute neutrophil count (ANC) >1.0x10^9/l without growth factor support for 7 days\n- Platelet count >75x10^9/l without transfusions for 7 days\n- Patient agrees not to participate in any other interventional study while on protocol treatment without approval of the Principal Investigator\n- Additional inclusion criteria cohort A: Additional inclusion criteria cohort A 1\tDiagnosis of a R/R PCNSL according to the WHO 2022 classification"}

Exclusion criteria

• {"criterion_text":"- The following DLBCL subtypes are not allowed: a) Patients with intravitreal lymphoma, b) Primary testicular lymphoma, c) Intravascular lymphoma, d) Epstein-barrvirus (EBV) driven lymphoma, e) Post-transplant LPDs\n- Significant renal dysfunction (estimated creatinine clearance < 45 ml/min after rehydration according to local practice)\n- Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, infection, hypertension, cancer, etc.)\n- Active or uncontrolled viral infection (Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), Human Immunodeficiency Virus (HIV), Coronavirus disease (COVID))\n- Hypersensitivity to the active substance.\n- Patients unable to swallow capsules or with diseases significantly affecting the gastrointestinal function.\n- History of active malignancy (other than lymphoma) requiring ongoing treatment during the past 5 years with the exception of basal carcinoma of the skin or stage 0 cervical carcinoma\n- Patient is pregnant, breast-feeding patients, or intending to become pregnant during participation in the study\n- Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule\n- Patient has received prior therapy with CRBN-modulating drug (eg, lenalidomide, avadomide/CC-122, pomalidomide, golcadomide (CC-99282)) within 5 half-lives or 4 weeks, whichever is shorter, prior to starting investigational product.\n- Severe cardiovascular disease (arrhythmias not well controlled with medication, congestive heart failure or symptomatic ischemic heart disease)\n- Severe pulmonary dysfunction\n- Severe neurological or psychiatric disease\n- Significant hepatic dysfunction (serum transaminases ≥ 3 times upper limit of normal or bilirubin ≥ 3 x ULN (unless bilirubin rise is due to Gilbert's syndrome))"}

Primary endpoints

• {"endpoint_text":"- Best overall response achieved during the first 13 treatment cycles","definition_or_measurement_approach":"Primary objective: a best observed ORR (complete remission and partial remission) of 40%, according to the IPCG response criteria among patients with R/R PCNSL and according to IPCG and Lugano criteria among patients with sCNSL"}

Secondary endpoints

• {"endpoint_text":"- Toxicity according to the CTCAE grading\n- Time to best response\n- PFS as measured from time of start study treatment until progression or death\n- OS as measured from time of start study treatment until death of any cause\n- DOR as measured from first documentation of response until relapse or progression or death\n- Functional status by MMSE and QoL EORTC QLQ-C30 and EORTC QLQ-BN20\n- Exploratory endpoint: PK of golcadomide in spinal fluid as compared to plasma\n- Exploratory endpoint: To examine the value of ctDNA in plasma and spinal fluid for detection of minimal residual disease and the correlation with clinical outcome\n- Exploratory endpoint: Correlation between mutational and GEP profiles and response to treatment","definition_or_measurement_approach":"Toxicity: graded according to CTCAE. Time to best response: time from start of treatment to best response. PFS: measured from time of start study treatment until progression or death. OS: measured from time of start study treatment until death of any cause. DOR: from first documentation of response until relapse/progression/death. Functional status and QoL: MMSE and EORTC QLQ-C30 and EORTC QLQ-BN20. PK: modelling of golcadomide in spinal fluid vs plasma. ctDNA: detection of minimal residual disease in plasma and spinal fluid and correlation with clinical outcome. Correlation analyses: between mutational and GEP profiles and response."}

Belgium

Earliest CTIS Part Ii Submission Date

06-05-2025

Latest Decision Or Authorization Date

02-06-2025

Processing Time Days

27

Number Of Sites

2

Number Of Participants

18

Netherlands

Earliest CTIS Part Ii Submission Date

22-05-2025

Latest Decision Or Authorization Date

02-06-2025

Processing Time Days

11

Number Of Sites

9

Number Of Participants

56

Primary sponsor

Full Name

Hemato-Oncologie voor Volwassenen Nederland (Hovon) Stichting

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands

Third parties

• {"country":"United States","full_name":"Foresight Diagnostics, Inc","duties_or_roles":"code:4","organisation_type":"Industry"}
• {"country":"United States","full_name":"QPS LLC","duties_or_roles":"code:4","organisation_type":"Pharmaceutical company"}
• {"country":"Netherlands","full_name":"Universitair Medisch Centrum Groningen","duties_or_roles":"Biobanking","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Netherlands","full_name":"Amsterdam UMC Stichting","duties_or_roles":"Pathology review","organisation_type":"Patient organisation/association"}
• {"country":"Ireland","full_name":"Bristol-Myers Squibb Pharmaceuticals Unlimited Company","duties_or_roles":"Providing IMP; code:3; code:4","organisation_type":"Pharmaceutical company"}