Recruiting

Phase 2

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

Sponsor:

Mayo Clinic

Code:

NCT06834373

Conditions

Large B-Cell Lymphoma With IRF4 Rearrangement

Recurrent Aggressive B-Cell Non-Hodgkin Lymphoma

Recurrent ALK-Positive Large B-Cell Lymphoma

Recurrent Diffuse Large B-Cell Lymphoma Activated B-Cell Type

Recurrent Diffuse Large B-Cell Lymphoma Associated With Chronic Inflammation

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Biospecimen Collection

Bone Marrow Aspiration

Bone Marrow Biopsy

Chimeric Antigen Receptor T-Cell Therapy

Computed Tomography

Study Details

Brief summary:

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.

Conditions

Large B-Cell Lymphoma With IRF4 Rearrangement

Recurrent Aggressive B-Cell Non-Hodgkin Lymphoma

Recurrent ALK-Positive Large B-Cell Lymphoma

Recurrent Diffuse Large B-Cell Lymphoma Activated B-Cell Type

Recurrent Diffuse Large B-Cell Lymphoma Associated With Chronic Inflammation

Study ID

NCT06834373

Start date

Apr 2, 2025

Status verified date

Jan, 2026

Completion date

Mar 3, 2027

Anticipated

Primary completion date

Mar 3, 2027

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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 Design

Enrollment

41 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

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.

Interventions

Biospecimen Collection

Undergo blood sample collection

Bone Marrow Aspiration

Undergo bone marrow aspiration and biopsy

Bone Marrow Biopsy

Undergo bone marrow aspiration and biopsy

Chimeric Antigen Receptor T-Cell Therapy

Undergo standard of care CAR-T therapy

Computed Tomography

Undergo CT or PET/CT

Golcadomide

Given PO

Leukapheresis

Undergo leukapheresis

Positron Emission Tomography

Undergo PET/CT

Rituximab

Given IV

Primary outcome measure

Disease control [ Time Frame: 2 cycles (cycle length = 28 days) ]

Central Contacts and Locations

Central contacts

Clinical Trials Referral Office

855-776-0015 mayocliniccancerstudies@mayo.edu

Locations

Mayo Clinic in Arizona

Recruiting

Scottsdale, Arizona, United States, 85259

Contacts

Clinical Trials Referral Office

855-776-0015 mayocliniccancerstudies@mayo.edu

Principal Investigator:

Javier L. Munoz, MD, MBA

Mayo Clinic in Florida

Recruiting

Jacksonville, Florida, United States, 32224-9980

Contacts

Clinical Trials Referral Office

855-776-0015 mayocliniccancerstudies@mayo.edu

Principal Investigator:

Muhamad Alhaj Moustafa, MD, MS

Mayo Clinic Health System in Albert Lea

Recruiting

Albert Lea, Minnesota, United States, 56007

Contacts

Clinical Trials Referral Office

855-776-0015 mayocliniccancerstudies@mayo.edu

Principal Investigator:

Mina Hanna, MD

Mayo Clinic Health Systems-Mankato

Recruiting

Mankato, Minnesota, United States, 56001

Contacts

Clinical Trials Referral Office

855-776-0015 mayocliniccancerstudies@mayo.edu

Principal Investigator:

Amrit B. Singh, MBBS

Mayo Clinic in Rochester

Recruiting

Rochester, Minnesota, United States, 55905

Contacts

Clinical Trials Referral Office

855-776-0015 mayocliniccancerstudies@mayo.edu

Principal Investigator:

Claire Tiger, MD, PhD

Mayo Clinic Health System-Eau Claire Clinic

Recruiting

Eau Claire, Wisconsin, United States, 54701

Contacts

Clinical Trials Referral Office

855-776-0015 mayocliniccancerstudies@mayo.edu

Principal Investigator:

Eyad S. Al-Hattab, MD

Mayo Clinic Health System-Franciscan Healthcare

Recruiting

La Crosse, Wisconsin, United States, 54601

Contacts

Clinical Trials Referral Office

855-776-0015 mayocliniccancerstudies@mayo.edu

Principal Investigator:

Scott H. Okuno, MD

More Information

Sponsor

Mayo Clinic

Last update posted

Jan 28, 2026

Last verified

Jan, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Mayo Clinic on 2026-01-28.