Golcadomide With Pemetrexed, Rituximab, and Dexamethasone for Relapsed and Refractory CNS Lymphomas

Starting soon · Phase 1

Conditions studied: Large B-cell Lymphoma, Central Nervous System Lymphoma

In brief

This research study is for people who have been diagnosed with large B-cell lymphoma of the central nervous system (CNS), which has either returned or is not responding to current treatment. Goldcadomide is a new experimental drug that works by binding to a specific protein inside cancer cells and helps stimulate immune cells that help fight cancer cells. It also has the ability to enter the central nervous system. It has shown promising safety and effectiveness when combined with standard of care chemotherapy. Participants will be treated with this study drug combined with standard of care chemotherapy. Participation in the research will last about 2.5 years. The purpose of this study is to help researchers learn if the study drug, Golcadomide, in combination with the standard of care regimen is a safe and effective way to treat large B-cell lymphoma with CNS involvement.

Key facts

Study ID

NCT07608731

Run by

Allison Winter

People needed

18

Starts

2026-06-01

Expected to finish

2029-09-01

Last updated by the study team

2026-05-27

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Participants or their legally acceptable representative must have signed and dated an IRB approved written ICF in accordance with regulatory, local, and institutional guidelines.
• Participants ≥ 18 years of age.
• Confirmed histopathological diagnosis of aggressive malignant B-cell lymphoma based upon a representative histology specimen according to the WHO classification. For participants with secondary CNS lymphoma, this can be confirmed by prior systemic biopsy. If a CNS lesion was not amenable for biopsy, imaging (e.g. MRI Brain ± MRI Full Spine) with CSF analysis for cytology may be used to confirm diagnosis, in lieu of a biopsy. Required. Acceptable histologies include:
• Large B-cell lymphoma NOS
• Diffuse large B-cell lymphoma (including GCB and ABC types)
• High-grade B-cell lymphoma with MYC and BCL2 rearrangements (double hit lymphomas)
• High-grade B-cell lymphoma NOS
• T-cell/histiocyte/rich large B-cell lymphoma (THRLBCL)
• EBV + DLBCL
• PMBCL
• Follicular Large B-Cell (previously referred to as Follicular Lymphoma, Grade 3B)
• Participants must have active CNS lymphoma for which this trial is planned. Confirmation of the histology in relapsed setting is not required but participants must have measurable disease per the International PCSNL Collaboration Group Criteria (Section 11.1), as evidenced by at least one of the following:
• CNS disease on MRI (brain or spine including parenchymal and leptomeningeal)
• Detectable in the CSF
• Detectable on ophthalmologic exam
• Participants must have received ≥ 1 prior systemic therapy for treatment of their CNS lymphoma. Participants who had systemic lymphoma and then relapsed with secondary CNS lymphoma must have received at least one prior line of therapy to specifically treat the CNS lymphoma.
• Participants must have received prior high dose methotrexate as a line of therapy OR have been ineligible for methotrexate therapy based on the investigator's discretion.
• Participants who have received methotrexate as their first line of therapy but are no longer eligible for ongoing methotrexate and have persistent disease are eligible
• ECOG performance status ≤ 0-3. PS 3 is allowed if it is disease related and not due to comorbidities or frailty and PS 4 is allowed if it is from CNS causing motor weakness and not due to comorbidities or frailty. (see Appendix I)
• Adequate bone marrow function, defined by the following laboratory parameters:
• Absolute neutrophil ≥ 1.5 x 109/L
• Platelet count ≥ 100 x 109/L
• Hemoglobin ≥ 8 g/dL
• Adequate organ function, defined by the following laboratory parameters:
• Adequate hepatic function, with transaminases (alanine aminotransferase [ALT], aspartate aminotransferase [AST], and gamma glutamyl transferase [GGT]) ≤ 2.5 times the upper limit of normal

You may not qualify if…

• Prior treatment toxicities not resolved to grade < 2 according to NCI CTCAE 6.0 (with the exception of alopecia or grade 2 sensory peripheral neuropathy).
• Participants receiving any other investigational agents.
• History of anaphylactic reactions or severe allergic reactions prohibiting further administration attributed to compounds of similar chemical or biologic composition to rituximab or other agents used in this study.
• Autologous stem cell transplant within 30 days of start of study drug (C1D1).
• CAR T-cell therapy within 90 days of start of study drug (C1D1).
• Previous allogeneic stem cell transplant
• Women who are pregnant or breastfeeding.
• Clinically significant autoimmune disease.
• Known seropositive and requiring anti-viral therapy for human immunodeficiency (HIV) virus.
• Malabsorption syndrome or other conditions that precludes enteral route of administration.
• Chemotherapy or radiation within 2 weeks of the first scheduled study treatment
• Participant is currently receiving warfarin. Particpants may begin screening if the plan is to change to an alternative anticoagulant such as a DOAC prior to enrollment.
• Participant has current treatment with strong cytochrome P450 3A4/5 (CYP3A4/5) modulators. The washout period for strong CYP3A4/5 modulators is 7 days or 5 half-lives (whichever is longer) before initiation of golcadomide.
• Evidence of other clinically significant uncontrolled condition(s) including, but not limited to:
• Uncontrolled and/or active systemic infection (viral, bacterial or fungal)
• Chronic hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment. Note: participants with serologic evidence of prior vaccination to HBV (i.e. hepatitis B surface (HBs) antigen negative-, anti-HBs antibody positive and anti-hepatitis B core (HBc) antibody negative) or positive anti-HBc antibody from intravenous immunoglobulins (IVIG) may participate.
• Other uncontrolled conditions including uncontrolled cardiovascular disease or arrhythmia, decompensated diabetes or COPD.

Where it is running

• Cleveland Clinic, Case Comprehensive Cancer Center — Cleveland, Ohio, United States

Full record on ClinicalTrials.gov

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