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

NCT07608731 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: CASE3425
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Large B-cell Lymphoma; Central Nervous System Lymphoma

Keywords

Golcadomide; Pemetrexed; Rituximab; Dexamethasone

Outcome Measures

Primary Outcomes (2)

• Safety of Golcadomide + Pemetrexed, Rituximab and Dexamethasone

  Safety is defined as rates of adverse events experienced by participants. Adverse event severity is graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE), Version 6.0.

  up to 6 cycles (up to 6 months)

• Identify the maximum tolerated dose of Golcadomide + Pemetrexed, Rituximab and Dexamethasone

  determined by the 3+3 dose escalation design

  up to 6 cycles (up to 6 months)

Secondary Outcomes (6)

• Overall response rate (ORR) by International Primary CNS Lymphoma Collaborative Group (IPCG) of Golca + PRD

  up to 18 months

• Disease control rate (DCR) by IPCG

  18 months

• Overall survival rate

  18 months

• Progression free survival rate

  18 months

• Proportion of participants designated for cellular therapy who receive cellular therapy

  18 months

Study Arms (1)

Golcadomide + Pemetrexed, Rituximab and Dexamethasone

EXPERIMENTAL

A 3+3 design will be used to identify the recommended phase 2 dose of Golcadomide in combination with Pemetrexed, Rituximab, and Dexamethasone. 3 participants will be enrolled in the first dose level. If these participants do not experience any dose limiting toxicities, then 3 more patients will be enrolled in the next dose level. If one or more participants experience dose limiting toxicities, then this dose will be considered the highest dose administered dose and 3 additional patients will be enrolled in the next lowest dose level. If 2 or more patients experience dose limiting toxicities, then the dose escalation will be stopped and 3 additional patients will enrolled in the next lowest dose level.

Drug: Golcadomide; Drug: Pemetrexed; Drug: Rituximab; Drug: Dexamethasone

Interventions

Golcadomide DRUG

To be taken orally daily on days 1-7 of the cycle Maximum 3 cycles but participants may received up to 3 additional cycles (for a total of up to 6 cycles) Cycle Length : 21 days Dose Levels: * Level -1 : 0.2milligrams/day * Level 1 : 0.2milligrams/day * Level 2 : 0.4milligrams/day

Golcadomide + Pemetrexed, Rituximab and Dexamethasone

Pemetrexed DRUG

To be given intravenously (IV) on day 1 of each cycle Maximum 3 cycles but participants may receive up to 3 additional cycles (for a total of up to 6 cycles) Cycle Length: 21 days Dose Level * Level -1 : 675 milligrams/square meter * Level 1 : 900 milligrams/square meter * Level 2 : 900 milligram/square meter

Golcadomide + Pemetrexed, Rituximab and Dexamethasone

Rituximab DRUG

To be given intravenously on day 1 of each cycle Maximum 3 cycles but participants may receive up to 3 additional cycles (for a total of up to 6 cycles) Cycle Length: 21 days Dose Level * Level -1 : 500 milligram/ square meter * Level 1 : 500 milligram/ square meter * Level 2 : 500 milligram/ square meter

Golcadomide + Pemetrexed, Rituximab and Dexamethasone

Dexamethasone DRUG

To be given orally on days 1-4 of each cycle Day 1 dose should be given at least 30 minutes before rituximab infusion Maximum 3 cycles but participants may receive up to 3 additional cycles (for a total of up to 6 cycles) Cycle Length: 21 days Dose Level * Level -1 : 10 milligrams * Level 1 : 10 milligrams * Level 2 : 10 milligrams

Golcadomide + Pemetrexed, Rituximab and Dexamethasone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

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)

Sponsors & Collaborators

• Allison Winter: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Cleveland Clinic, Case Comprehensive Cancer Center

Cleveland, Ohio, 44122, United States

Location

MeSH Terms

Interventions

Pemetrexed; Rituximab; Dexamethasone

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Allison M Winter, MD

  Cleveland Clinic, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Allison M Winter, MD

CONTACT

(216) 445-4635; wintera2@ccf.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 20, 2026
• First Posted: May 27, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): April 1, 2029
• Study Completion (Estimated): September 1, 2029
• Last Updated: May 27, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data included in the peer-reviewed publication will be publicly available indefinitely. No raw data will be shared.
• Access Criteria: A peer-reviewed publication will be made available according to the publishing journal's specifications. CCF personal will not share study data apart that which has been published publicly.

Locations

US (1)