A phase 2 study of the effectiveness of golcadomide (CC-99282) for patients with large B-cell lymphoma in the brain

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Hemato-Oncologie voor Volwassenen Nederland (Hovon) Stichting

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15], Diseases [C] - Neoplasms [C04], Diseases [C] - Nervous System Diseases [C10]

Trial duration

16 Sep 2025 → ongoing

Decision date (initial)

2025-06-02

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Bristol-Myers Squibb Services Unlimited Company

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy, Pharmacokinetic, Pharmacogenetic

The primary objective of the study is 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 objectives 9

1. To determine toxicity according to the CTCAE grading
2. To evaluate time to best response
3. To evaluate PFS as measured from time of start study treatment until progression or death
4. To evaluate OS as measured from time of start study treatment until death of any cause
5. To evaluate DOR as measured from first documentation of response until relapse or progression or death
6. To assess functional status and QoL
7. Exploratory objective: To model PK of golcadomide in spinal fluid as compared to plasma
8. Exploratory objective: To examine the value of ctDNA in plasma and spinal fluid for detection of MRD and the correlation with clinical outcome
9. Exploratory objective: To evaluate correlation between mutational and GEP profiles and response to treatment

Conditions and MedDRA coding

Relapsed primary large B-cel lymphoma of the central nervous system

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. ≥ 18 years as minimum age
2. WHO-performancestatus ≤ 2
3. Patient must understand and voluntarily sign an Informed Concent Form (ICF) prior to any study related assessments/procedures being conducted
4. Patient is willing and able to adhere to the study visit schedule and other protocol requirements
5. Haemoglobin > 5 mmol/l
6. Absolute neutrophil count (ANC) >1.0x10^9/l without growth factor support for 7 days
7. Platelet count >75x10^9/l without transfusions for 7 days
8. Patient agrees not to participate in any other interventional study while on protocol treatment without approval of the Principal Investigator
9. Additional inclusion criteria cohort A: Additional inclusion criteria cohort A 1 Diagnosis of a R/R PCNSL according to the WHO 2022 classification
10. Additional inclusion criteria cohort A: Patients must have received prior high-dose methotrexate based chemotherapy.
11. 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
12. Additional inclusion criteria cohort B: Progression or relapse with CNS localization with or without systemic relapse
13. Additional inclusion criteria cohort B: 3 Diagnosis 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

Exclusion criteria 14

1. 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
2. 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
3. Patient is pregnant, breast-feeding patients, or intending to become pregnant during participation in the study
4. Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule
5. 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.
6. Severe cardiovascular disease (arrhythmias not well controlled with medication, congestive heart failure or symptomatic ischemic heart disease)
7. Severe pulmonary dysfunction
8. Severe neurological or psychiatric disease
9. 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))
10. Significant renal dysfunction (estimated creatinine clearance < 45 ml/min after rehydration according to local practice)
11. Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, infection, hypertension, cancer, etc.)
12. Active or uncontrolled viral infection (Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), Human Immunodeficiency Virus (HIV), Coronavirus disease (COVID))
13. Hypersensitivity to the active substance.
14. Patients unable to swallow capsules or with diseases significantly affecting the gastrointestinal function.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Best overall response achieved during the first 13 treatment cycles

Secondary endpoints 9

1. Toxicity according to the CTCAE grading
2. Time to best response
3. PFS as measured from time of start study treatment until progression or death
4. OS as measured from time of start study treatment until death of any cause
5. DOR as measured from first documentation of response until relapse or progression or death
6. Functional status by MMSE and QoL EORTC QLQ-C30 and EORTC QLQ-BN20
7. Exploratory endpoint: PK of golcadomide in spinal fluid as compared to plasma
8. 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
9. Exploratory endpoint: Correlation between mutational and GEP profiles and response to treatment

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Hemato-Oncologie voor Volwassenen Nederland (Hovon) Stichting

Sponsor organisation

Hemato-Oncologie voor Volwassenen Nederland (Hovon) Stichting

Address

Dr. Molewaterplein 40

City

Rotterdam

Postcode

3015GD

Country

Netherlands

Scientific contact point

Organisation

Hemato-Oncologie voor Volwassenen Nederland (Hovon) Stichting

Contact name

M. Nijland

Public contact point

Organisation

Hemato-Oncologie voor Volwassenen Nederland (Hovon) Stichting

Contact name

HOVON

Third parties 5

Locations

2 EU/EEA countries · 10 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 13 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications