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Large B-cell LymphomaPhase 1NCT07608731

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

A Phase 1 study testing Golcadomide, Pemetrexed and Rituximab in people with Large B-cell Lymphoma and Central Nervous System Lymphoma, run by Allison Winter at 1 site in United States.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Golcadomide, Pemetrexed and Rituximab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
1 siteUnited States
Study dates
Oct 2026to Sep 2029
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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
  • Bilirubin ≤1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin)
  • Calculated creatinine clearance > 45 mL/min by the Cockcroft-Gault equation.
  • Treating investigator must specify at screening:
  • If the intent of therapy is a bridge to cellular therapy or to complete all six cycles of therapy. If bridge to cellular therapy is planned, the type of cellular therapy should also be specified at this time.
  • If the r/r CNS lymphoma is primary or secondary
  • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use two methods of contraception simultaneously from signing the ICF, at least 28 days before starting golcadomide, throughout the study, for up to 28 days following the last dose of golcadomide, and for 12 months after the last dose of rituximab, whichever is longer.. Two methods of contraception must include one highly effective method and one additional effective (barrier method).
  • A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (< 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries, fallopian tubes, and/or uterus).
  • Examples of contraceptive methods include highly effective methods such as oral, injectable, or implantable hormonal contraceptive; tubal ligation; intrauterine device; vasectomized partner and barrier methods with spermicide.
  • The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.
  • Must agree to pregnancy testing per protocol. This applies even if the participant practices true abstinence from heterosexual contact.
  • Agree to abstain from breastfeeding or providing breast milk while on golcadomide and 28 days after discontinuation of golcadomide and according to the approved
  • For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as defined below:
  • With female partners of childbearing potential, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of < 1% per year during the treatment period and for at least 28 days after the last dose of study intervention or 90 days for rituximab, whichever is longer. Men must refrain from donating sperm during this same period.
  • With pregnant female partners, men must remain abstinent or use a condom during the treatment period and for at least 28 days after the last dose of study intervention or 90 days for rituximab, whichever is longer.
  • The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.

Who cannot join

  • 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
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  • 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. Participants 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.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Allison M Winter, MD contact

(216) 445-4635

wintera2@ccf.org

United States1 site

  • Cleveland Clinic, Case Comprehensive Cancer Center

    Cleveland, Ohio, 44122

    Allison M Winter, MD, (216) 445-4635, wintera2@ccf.org

    Allison Winter, MD

Other trials in United States

About this study

Official title: Phase I Pilot Trial of Golcadomide With Pemetrexed, Rituximab, and Dexamethasone for Relapsed and Refractory CNS Lymphomas

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.

Read the detailed description

People with systemic diffuse large B-cell lymphoma (DLCBL) can either have a a disease that involves the central nervous system or does not involve the central nervous system. The disease could also be only located in the central nervous system. The central nervous system lymphoma includes disease within the brain, meninges, cranial nerves, cerebrospinal fluid, spinal cord, and/or intraocular. For people with disease that involves the CNS it can be difficult to treat. This is because many effective lymphoma treatments do not cross the blood-brain barrier (BBB).

In general there is a large unmet need for effective and feasible therapies for CNS lymphomas. This study addresses these gaps by combining standard of care chemotherapy with Golcadomide.This approach aims to provide a feasible and potentially effective treatment option for a population with historically poor outcomes.

The purpose of this study is to find out the safety and efficacy of Golcadomide in combination with drugs in the standard care chemotherapy. Another goal is to find the recommended phase 2 dose of Golcadomide in combination with standard of care chemotherapy.

Being tested
Golcadomide, Pemetrexed, Rituximab, Dexamethasone
Keywords
Golcadomide, Pemetrexed, Rituximab, Dexamethasone

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GolcadomideDrug

    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

  • PemetrexedDrug

    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

  • RituximabDrug

    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

  • DexamethasoneDrug

    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
Study groups in NCT07608731
Study groupRoleWhat they receive
Golcadomide + Pemetrexed, Rituximab and DexamethasoneExperimentalA 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.
Receives: Drug: Golcadomide; Drug: Pemetrexed; Drug: Rituximab; Drug: Dexamethasone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: up to 6 cycles (up to 6 months)

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

    determined by the 3+3 dose escalation design

    Measured: up to 6 cycles (up to 6 months)

Secondary outcomes (6)

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

    ORR includes complete response (CR), Unconfirmed CR (CRu), partial response (PR), \& disease control rate (DCR), according to the 2005 IPCG Response Criteria.

    CR: complete disappearance of abnormalities on gadolinium-enhanced MRI, no contrast enhancement in brain imaging, no corticosteroid dose, normal eye examination \& negative Cerebrospinal fluid (CSF) cytology.

    CRu: fulfilling criteria for CR but with minimum to no contrast enhancement in brain imaging, continuing use of corticosteroid therapy, normal to minor retinal pigment epithelium (RPE) abnormality, \& negative CSF cytology.

    PR: greater than 50% decrease in contrast-enhancing lesion compared to baseline imaging, normal to minor RPE abnormality, negative CSF cytology \& no new sites of disease.

    SD: less than a PR but is not progressive disease.

    Measured: up to 18 months

  2. Disease control rate (DCR) by IPCG

    DCR is the percentage of participants whose cancer did not get worse after treatment (i.e. the percentage of participants who had CR, PR, or , SD, as defined below), and this will be measured by the IPCG response criteria.

    CR: complete disappearance of abnormalities on gadolinium-enhanced MRI, no contrast enhancement in brain imaging, no corticosteroid dose, normal eye examination \& negative Cerebrospinal fluid (CSF) cytology.

    CRu: fulfilling criteria for CR but with minimum to no contrast enhancement in brain imaging, continuing use of corticosteroid therapy, normal to minor retinal pigment epithelium (RPE) abnormality, \& negative CSF cytology.

    PR: greater than 50% decrease in contrast-enhancing lesion compared to baseline imaging, normal to minor RPE abnormality, negative CSF cytology \& no new sites of disease.

    SD: less than a PR but is not progressive disease.

    Measured: 18 months

  3. Overall survival rate

    Overall survival (OS) is defined as the duration of time from start of treatment to time of death from any cause for participants who complete treatment.

    Measured: 18 months

  4. Progression free survival rate

    Progression-Free Survival (PFS) is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first, for participants who complete treatment.

    Measured: 18 months

  5. Proportion of participants designated for cellular therapy who receive cellular therapy

    The number of participants intended for cellular therapy who receive cellular therapy will be described as a proportion.

    Measured: 18 months

  6. Proportion of participants who have a successful mobilization of autologous stem cell transplant

    The number of participants who undergo mobilization for collection of autologous stem cell transplant following treatment with Golca + RPD and have successful mobilization will be described as proportion.

    Measured: 18 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 May 2026
  2. Study startOct 2026 (estimated)
  3. Primary completionApr 2029 (estimated)
  4. Study completionSep 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
18 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07608731
Sponsor's protocol ID
CASE3425
Status last verified
May 2026
First submitted
20 May 2026
Last updated
21 Aug 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: All IPD that underlie results in publication will be shared with the FDA, UH, and Bristol Myers Squibb, who are the suppliers of the investigational product. Any patient data shared will be deidentified.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Golcadomide, Pemetrexed and Rituximab in people with Large B-cell Lymphoma and Central Nervous System Lymphoma, run by Allison Winter at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 40 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 21 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Allison M Winter, MD ((216) 445-4635, wintera2@ccf.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety of Golcadomide + Pemetrexed, Rituximab and Dexamethasone (time frame: up to 6 cycles (up to 6 months)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07608731.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Aug 2026.

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