Golcadomide and Rituximab as Bridging Therapy for Relapsed or Refractory Aggressive B-cell Non-Hodgkin Lymphoma Before CAR T-cell Therapy

January 26, 2026 updated by: Mayo Clinic

Phase 2 Study of Golcadomide With Rituximab as a Bridging Therapy Prior to CAR-T for Patients With Relapsed or Primary Refractory Aggressive B-Cell Non-Hodgkin Lymphoma (NHL)

This phase II trial tests the effectiveness of golcadomide and rituximab as bridging treatment before chimeric antigen receptor (CAR) T-cell therapy in patients with aggressive B-cell non-Hodgkin lymphoma that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). Patients that are able to receive CAR T-cell therapy have a potential for cure, however, many will not be qualified to receive therapy due to relapse. Bridging therapy is therapy intended to transition a patient from one therapy or medication to another or maintain their health or status until they are a candidate for a therapy or have decided on a therapy. Golcadomide may help block the formation, growth or spread of cancer cells. Rituximab is a monoclonal antibody. It binds to a protein called CD20, which is found on B cells (a type of white blood cell) and some types of cancer cells. This may help the immune system kill cancer cells. Giving golcadomide and rituximab as bridging therapy before CAR T-cell therapy may kill more tumor cells and may improve the chance of proceeding to CAR T-cell therapy in patients with relapsed or refractory aggressive B-cell non-Hodgkin lymphoma.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVE:

I. Evaluate efficacy as measured by the disease control rate (complete metabolic response [CMR], partial metabolic response [PMR], and no metabolic response [NMR]) by Lugano 2014 positron emission tomography (PET)-computed tomography (CT) based assessment after 2 cycles of therapy.

SECONDARY OBJECTIVES:

I. To further evaluate clinical efficacy as measured by overall response rate (ORR), complete response (CMR) rate, disease control rate by Lugano PET-CT based criteria.

II. To evaluate the safety and tolerability of golcadomide + rituximab combination therapy as measured by the incidence and severity of treatment related adverse events (TRAE).

III. To evaluate efficacy as a bridging therapy as measured by the number of patients proceeding to CAR-T and response to CAR-T.

IV. To evaluate duration of response, progression-free survival, and overall survival.

EXPLORATORY OBJECTIVES:

I. Improvement of symptoms (compressive, pain, B symptoms [fever, night sweats, weight loss]) associated with the disease as determined by the investigator.

II. To evaluate the diversity of CAR-T products received in patients proceeding to CAR-T.

OUTLINE:

Patients receive golcadomide orally (PO) once daily (QD) on days 1-14 of each cycle and rituximab intravenously (IV) on days 1, 8, 15 and 22 of cycle 1 and then on day 1 of all subsequent cycles. Cycles repeat every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.

ELIGIBLE FOR CAR-T: After 2 cycles, patients undergo leukapheresis and may receive 1-2 additional cycles of golcadomide and rituximab prior to undergoing standard of care CAR-T therapy.

INELIGIBLE FOR CAR-T: After 2 cycles, patients receive golcadomide PO QD on days 1-14 of each cycle and rituximab IV on day 1 of each cycle. Cycles repeat every 28 days for up to 10 additional cycles of golcadomide (cycles 3-12) and up to 3 additional cycles of rituximab (cycles 3-5) in the absence of disease progression or unacceptable toxicity.

Patients also undergo blood sample collection and PET/CT or CT throughout the study. Additionally, patients may undergo bone marrow aspiration and biopsy as clinically indicated.

After completion of study treatment, patients are followed up at 28 days. CAR-T ineligible patients are followed up every 3 months until progression or subsequent treatment, then every 6 months for up to 2 years. CAR-T eligible patients are followed up at 180 days after CAR-T then every 6 months for up to 2 years.

Study Type

Interventional

Enrollment (Estimated)

41

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85259
        • Recruiting
        • Mayo Clinic in Arizona
        • Contact:
        • Principal Investigator:
          • Javier L. Munoz, MD, MBA
    • Florida
      • Jacksonville, Florida, United States, 32224-9980
        • Recruiting
        • Mayo Clinic in Florida
        • Contact:
        • Principal Investigator:
          • Muhamad Alhaj Moustafa, MD, MS
    • Minnesota
      • Albert Lea, Minnesota, United States, 56007
        • Recruiting
        • Mayo Clinic Health System in Albert Lea
        • Principal Investigator:
          • Mina Hanna, MD
        • Contact:
      • Mankato, Minnesota, United States, 56001
        • Recruiting
        • Mayo Clinic Health Systems-Mankato
        • Contact:
        • Principal Investigator:
          • Amrit B. Singh, MBBS
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Mayo Clinic in Rochester
        • Contact:
        • Principal Investigator:
          • Claire Tiger, MD, PhD
    • Wisconsin
      • Eau Claire, Wisconsin, United States, 54701
        • Recruiting
        • Mayo Clinic Health System-Eau Claire Clinic
        • Contact:
        • Principal Investigator:
          • Eyad S. Al-Hattab, MD
      • La Crosse, Wisconsin, United States, 54601
        • Recruiting
        • Mayo Clinic Health System-Franciscan Healthcare
        • Contact:
        • Principal Investigator:
          • Scott H. Okuno, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age ≥ 18 years

  • Confirmed pathology diagnosis according to 2016 World Health Organization (WHO) classification including patients with diseases listed below with relapsed, progressive and/or refractory disease (Cheson et al. 2014) following treatment with one or two prior lines of standard therapy, no more than two lines of therapy are permitted:

    • Diffuse large B-cell lymphoma not otherwise specified (NOS) including:

      • Transformed lymphoma
      • Germinal center B-cell type
      • Activated B-cell type
    • High-grade B-cell lymphoma (HGBCL), NOS
    • High grade B-cell lymphoma with MYC and BCL2 translocation
    • Primary mediastinal (thymic) large B-cell lymphoma
    • Grade 3B follicular lymphoma
    • T-cell/histiocyte-rich large B-cell lymphoma
    • Large B-cell lymphoma with IRF4 rearrangement
    • Primary cutaneous diffuse large B-cell lymphoma (DLBCL), leg type
    • Epstein-Barr virus (EBV) positive DLBCL, NOS
    • DLBCL associated with chronic inflammation
    • Intravascular large B-cell lymphoma
    • ALK positive large B-cell lymphoma
    • NOTE: Richters transformation patients are excluded

  • Measurable disease by PET-CT with at least one lymph node or other type of lesion that has a size > 1.5 cm in the transverse diameter, as defined by Lugano classification

    • NOTE: Tumor lesions in a previously irradiated area are not considered measurable disease; Disease that is measurable by physical examination only is not eligible
  • Patient is potentially eligible for CAR-T therapy as determined by treating physician
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
  • Hemoglobin > 7.0 g/dL (obtained ≤ 14 days prior to registration)
  • Absolute neutrophil count (ANC) ≥ 1000/mcL (obtained ≤ 14 days prior to registration); growth factor support allowed at physician discretion
  • Platelet count ≥ 75,000/mcL (obtained ≤ 14 days prior to registration)
  • Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (obtained ≤ 14 days prior to registration); if total bilirubin is > 1.5 ULN, direct bilirubin must be normal
  • Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤ 2.5 x ULN (≤ 5 x ULN if there is evidence of parenchymal liver involvement with lymphoma) (obtained ≤ 14 days prior to registration)
  • Calculated creatinine clearance ≥ 45 ml/min using the Cockcroft-Gault formula (obtained ≤ 14 days prior to registration)

  • Have 2 negative pregnancy tests as verified by the investigator prior to starting CC-99282:

    • A negative serum pregnancy test (sensitivity of at least 25 mIU/mL) at screening (between 10 to 14 days prior to cycle 1 day 1)
    • A negative serum or urine pregnancy test (investigator's discretion) within 24 hours prior to cycle 1 day 1 of study treatment
  • Provide written informed consent
  • Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
  • Subjects must agree not to donate blood while receiving golcadomide, during dose interruptions and for ≥ 28 days following the last dose of golcadomide

Exclusion Criteria:

  • Any of the following because this study involves an investigational agent that has known genotoxic, mutagenic, and teratogenic effects:

    • Pregnant persons
    • Nursing persons

  • Persons of childbearing potential (and persons able to father a child) who are unwilling to employ adequate contraception

    • Persons of childbearing potential (PCBP) unwilling to use two reliable forms of contraception simultaneously or to practice complete abstinence (true abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence [e.g., calendar, ovulation, symptothermal or postovulation methods] and withdrawal are not acceptable methods of contraception) from heterosexual contact during the following time periods related to this study:
    • For ≥ 28 days before starting treatment, during treatment and dose interruptions, and for ≥ 28 days after the last dose of golcadomide

    • Examples of highly effective methods of contraception:

      • Intrauterine device (IUD)
      • Hormonal (birth control pills, injections, implants, levonorgestrel-releasing intrauterine system [IUS], medroxyprogesterone acetate depot injections, ovulation inhibitory
      • Progesterone-only pills [e.g., desogestrel])
      • Tubal ligation
      • Partner's vasectomy

    • Examples of additional effective methods:

      • Male condom
      • Diaphragm
      • Cervical cap
    • Persons who can father a child unwilling to practice complete abstinence (true abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence [e.g., calendar, ovulation, symptothermal or post-ovulation methods] and withdrawal are not acceptable methods of contraception.) or unwilling to use a condom during sexual contact with a pregnant person or a PCBP during treatment and dose interruptions, and for > 28 days following the last dose of golcadomide, even if they have undergone a successful vasectomy
    • Persons who can father a child and are unwilling to refrain from donating semen or sperm while receiving golcadomide, during dose interruptions, or for ≥ 28 days following the last dose of golcadomide
  • Life expectancy < 3 months

  • Any of the following prior therapies:

    • Any prior CAR-T or other T-cell targeting treatment (approved or investigational) ≤ 4 weeks prior to registration

    • Any prior systemic anti-cancer treatment (approved or investigational) ≤ 5 half-lives or 4 weeks prior to registration, whichever is shorter

      • Exception: Monoclonal and bispecific antibodies is acceptable
    • Prior therapy with golcadomide ≤ 4 weeks prior to registration
    • Prior autologous stem cell transplantation (SCT) ≤ 3 months prior to registration. If subject had autologous SCT > 3 months prior to the start of registration, any treatment-related toxicity is unresolved (grade > 1)
    • Major surgery ≤ 3 weeks prior to registration
    • Chemotherapy ≤ 2 weeks prior to registration
    • Concomitant radiation therapy; local palliative radiotherapy is permitted
  • Co-morbid systemic illnesses or other severe concurrent disease or cancer which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens

  • Impaired cardiac function or clinically significant cardiac diseases including, but not limited to:

    • Symptomatic congestive heart failure
    • History of myocardial infarction ≤ 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
    • Unstable angina pectoris
    • Cardiac arrhythmia

  • Uncontrolled intercurrent non-cardiac illness including, but not limited to:

    • Ongoing or active infection
    • Psychiatric illness/social situations
    • Dyspnea at rest due to complications of advanced malignancy or other disease that requires continuous oxygen therapy (such as interstitial lung disease or chronic obstructive pulmonary disease [COPD])
    • Any other conditions that would limit compliance with study requirements
  • Subject had prior allogeneic SCT with either standard or reduced intensity conditioning ≤ 6 months prior to registration. If subject had prior allogeneic SCT > 6 months prior to registration, any treatment-related toxicity is unresolved (grade >1)
  • Immunocompromised patients and patients known to be HIV positive and currently receiving antiretroviral therapy, as there is currently no safety data in HIV positive patients

  • Subject has known chronic active hepatitis B or C virus (HBV/HCV) infection

    • Exception: Patients with HBV and an undetectable viral load who are on suppressive therapy and/or those with HCV and an undetectable viral load are allowed
  • Concurrent administration of strong or moderate CYP3A4/5 inhibitors and inducers within 14 days or 5 half-lives, whichever is longer before the study treatment administration

  • Receiving any other investigational agent which would be considered as a treatment for lymphoma.

    • Exception: Corticosteroids are allowed
  • Active second malignancy requiring treatment that would interfere with the assessment of the response of the primary cancer or interpretation of the safety of this protocol therapy

  • History of deep venous thrombosis/embolism, threatening thromboembolism or known thrombophilia. Patients with a history of deep vein thrombosis (DVT)/pulmonary embolism (PE) or thrombophilia may still participate if they are willing to be on full anticoagulation during treatment. Full anticoagulation is defined as Warfarin, factor X inhibitors, or low molecular weight heparin at therapeutic doses. The rationale for this requirement is that golcadomide therapy is associated with an increased risk of thrombosis. Patients with no history of DVT/PE or thrombophilia are not required to take anticoagulation and/or anti-platelet prophylaxis

    • NOTE: If a patient develops a thrombotic event, they must be able and willing to receive anticoagulation therapy with aspirin 81-325 mg daily prophylaxis, low molecular weight heparin, factor X inhibitors or Warfarin. This is due to an increased risk of thrombosis in patients treated with golcadomide without prophylaxis
  • Live COVID-19 vaccine administered ≤ 28 days prior to registration

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment (golcadomide, rituximab)

Patients receive golcadomide PO QD on days 1-14 of each cycle and rituximab IV on days 1, 8, 15 and 22 of cycle 1 and then on day 1 of all subsequent cycles. Cycles repeat every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.

ELIGIBLE FOR CAR-T: After 2 cycles, patients undergo leukapheresis and may receive 1-2 additional cycles of golcadomide and rituximab prior to undergoing standard of care CAR-T therapy.

INELIGIBLE FOR CAR-T: After 2 cycles, patients receive golcadomide PO QD on days 1-14 of each cycle and rituximab IV on day 1 of each cycle. Cycles repeat every 28 days for up to 10 additional cycles of golcadomide (cycles 3-12) and up to 3 additional cycles of rituximab (cycles 3-5) in the absence of disease progression or unacceptable toxicity.

Patients also undergo blood sample collection and PET/CT or CT throughout the study. Additionally, patients may undergo bone marrow aspiration and biopsy as clinically indicated.
Procedure: Biospecimen Collection
Undergo blood sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Procedure: Leukapheresis
Undergo leukapheresis
Other Names:
  • Leukocytopheresis
  • Therapeutic Leukopheresis
  • Leukocyte Adsorptive Apheresis
  • White Blood Cell Reduction Apheresis
Biological: Rituximab
Given IV
Other Names:
  • Rituxan
  • MabThera
  • ABP 798
  • BI 695500
  • C2B8 Monoclonal Antibody
  • Chimeric Anti-CD20 Antibody
  • CT-P10
  • IDEC-102
  • IDEC-C2B8
  • IDEC-C2B8 Monoclonal Antibody
  • Monoclonal Antibody IDEC-C2B8
  • PF-05280586
  • Riabni
  • Rituximab ABBS
  • Rituximab ARRX
  • Rituximab Biosimilar ABP 798
  • Rituximab Biosimilar BI 695500
  • Rituximab Biosimilar CT-P10
  • Rituximab Biosimilar GB241
  • Rituximab Biosimilar IBI301
  • Rituximab Biosimilar JHL1101
  • Rituximab Biosimilar PF-05280586
  • Rituximab Biosimilar RTXM83
  • Rituximab Biosimilar SAIT101
  • Rituximab Biosimilar SIBP-02
  • rituximab biosimilar TQB2303
  • Rituximab PVVR
  • Rituximab-arrx
  • Rituximab-pvvr
  • RTXM83
  • Ruxience
  • Truxima
  • Rixathon
  • Ikgdar
  • Mabtas
  • Rituximab-abbs
  • BI-695500
  • BI695500
  • Blitzima
  • IDEC 102
  • IDEC102
  • PF 05280586
  • PF05280586
  • Ritemvia
  • Rituximab-blit
  • Rituximab-rite
  • Rituximab-rixa
  • Rituximab-rixi
  • Riximyo
  • RTXM 83
  • RTXM-83
  • ABP-798
  • ABP798
  • CT P10
  • CTP10
  • GP 2013
  • GP-2013
  • GP2013
  • Rituximab Biosimilar GP2013
Procedure: Positron Emission Tomography
Undergo PET/CT
Other Names:
  • Medical Imaging, Positron Emission Tomography
  • PET
  • PET Scan
  • Positron Emission Tomography Scan
  • Positron-Emission Tomography
  • PT
  • Positron emission tomography (procedure)
Procedure: Computed Tomography
Undergo CT or PET/CT
Other Names:
  • CT
  • CAT
  • CAT Scan
  • Computed Axial Tomography
  • Computerized Axial Tomography
  • Computerized Tomography
  • CT Scan
  • tomography
  • Computerized axial tomography (procedure)
  • Computerized Tomography (CT) scan
Procedure: Bone Marrow Aspiration
Undergo bone marrow aspiration and biopsy
Procedure: Bone Marrow Biopsy
Undergo bone marrow aspiration and biopsy
Other Names:
  • Biopsy of Bone Marrow
  • Biopsy, Bone Marrow
Drug: Golcadomide
Given PO
Other Names:
  • BMS-986369
  • BMS 986369
  • BMS986369
  • CC -99282
  • CC 99282
  • CC99282
  • CelMod CC-99282
  • Cereblon E3 Ubiquitin Ligase Modulating Agent CC-99282
  • Cereblon E3 Ubiquitin Ligase Modulating Drug CC-99282
  • Cereblon Modulator CC-99282
Biological: Chimeric Antigen Receptor T-Cell Therapy
Undergo standard of care CAR-T therapy
Other Names:
  • CAR T Infusion
  • CAR T Therapy
  • CAR T-cell Therapy
  • Chimeric Antigen Receptor T-cell Infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease control
Time Frame: 2 cycles (cycle length = 28 days)
Will be defined as a complete metabolic response (CMR), partial metabolic response (PMR), or no metabolic response (NMR) by Lugano 2014 PET-CT.
2 cycles (cycle length = 28 days)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease control rate
Time Frame: Up to 2 years
Will be estimated by the total number of patients who achieve a CMR, PMR, or NMR by Lugano 2014 positron emission tomography (PET)/computed tomography (CT) divided by the total number of evaluable patients.
Up to 2 years
Complete response rate
Time Frame: Up to 2 years
Will be assessed by the total number of patients who achieve a CMR by Lugano 2014 PET/CT.
Up to 2 years
Overall response rate
Time Frame: Up to 2 years
Will be assessed by the total number of patients who achieve a CMR or PMR by Lugano 2014 PET/CT divided.
Up to 2 years
The proportion of patients proceeding to chimeric antigen receptor T-cell (CART)
Time Frame: Up to 2 years
Will be assessed by the total number of patients who proceed to CART divided by the total number of evaluable patients.
Up to 2 years
Overall response rate to CART
Time Frame: Up to 2 years
Will be assessed by the total number of patients who achieve a CMR or PMR by Lugano 2014 PET/CT after CART.
Up to 2 years
Duration of response
Time Frame: Up to 2 years
Duration of response is defined for all evaluable patients who have achieved an objective response as the date at which the patient's objective status is first noted to be either a CMR or PMR to first documentation of disease progression.
Up to 2 years
Progression-free survival (PFS)
Time Frame: Up to 2 years
Progression-free survival is defined as the time from registration to first documentation of disease progression (PMD or PD) or death due to any cause in the absence of documented progression
Up to 2 years
Overall survival (OS)
Time Frame: From registration to death due to any cause, assessed up to 2 years
Overall survival is defined as the time from registration to death due to any cause.
From registration to death due to any cause, assessed up to 2 years
Incidence of adverse events (AEs)
Time Frame: Up to 30 days after last dose of study treatment
Will be evaluated using the Common Terminology Criteria for Adverse Events (CTCAE). The maximum grade for each type of AE will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the AE(s) to the study treatment will be taken into consideration and treatment related AEs will be evaluated.
Up to 30 days after last dose of study treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mayo Clinic

Investigators

  • Principal Investigator: Claire Tiger, MD, PhD, Mayo Clinic

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 2, 2025

Primary Completion (Estimated)

March 3, 2027

Study Completion (Estimated)

March 3, 2027

Study Registration Dates

First Submitted

February 14, 2025

First Submitted That Met QC Criteria

February 14, 2025

First Posted (Actual)

February 19, 2025

Study Record Updates

Last Update Posted (Actual)

January 28, 2026

Last Update Submitted That Met QC Criteria

January 26, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MC230813 (Other Identifier: Mayo Clinic)
  • NCI-2025-01094 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • 24-005122 (Other Identifier: Mayo Clinic Institutional Review Board)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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