CC-99282 + Rituximab Early Post CART for Non-Hodgkin's Lymphoma

February 24, 2026 updated by: Nathan Denlinger

Early, Risk Adapted CC-99282 + Rituximab Post CAR T-Cell Therapy for Non-Hodgkin's Lymphoma

This phase I trial tests the safety, side effects and best dose of CC-99282 with rituximab for the treatment of patients who have received chimeric antigen receptor (CAR) T cell therapy for non-Hodgkins lymphoma and in whom have had a sub-optimal response early on to CAR T-cell therapy. Immunotherapy with CC-99282 may induce changes in the body's immune system and may interfere with the ability of tumor cells to grow and spread. 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 CC-99282 with rituximab may be a safe and effective treatment option for patients who have received CAR-T cell therapy for relapsed or refractory non-Hodgkin's lymphoma.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVE:

I. To determine the safety profile and maximum tolerated dose (MTD) of early, risk adapted golcadomide (CC-99282)/rituximab for patients with relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL) post-commercial CD19.CAR-T infusion.

SECONDARY OBJECTIVES:

I. To perform a preliminary efficacy analysis of CC-99282 and rituxan early post CD19.CAR-T defined as the progression free survival (PFS) rate at day+150 post initiation of CC-99282.

II. To describe disease response rates in patients with active disease who are treated with CC-99282 + rituximab.

III. To estimate PFS in subjects treated with CC-99282 + rituximab. IV. To estimate the overall survival (OS) in subjects treated with CC-99282 + rituximab.

EXPLORATORY OBJECTIVES:

I. To describe CD19.CAR-T cell expansion and persistence following treatment with CC-99282/rituximab.

II. To evaluate CC-99282/rituximab's effect on CAR T-cells and other immune cell subsets composition and how this effects clinical outcomes.

III. To evaluate CC-99282/rituximab's effect on CAR T-cell and other immune cell subset function and how this effects clinical outcomes.

IV. To evaluate CC-99282/rituximab's effect on the tumor microenvironment (TME) and how this effects clinical outcomes.

OUTLINE: This is a dose-escalation study of CC-99282 in combination with fixed-dose rituximab.

Patients receive rituximab intravenously (IV) on day 1 of each cycle and CC-99282 orally (PO) once daily (QD) on days 1-14 of each cycle. Treatment repeats every 28 days for up to 6 cycles of rituximab and up to 26 cycles of CC-99282 in the absence of disease progression or unacceptable toxicity. Patients also undergo positron emission tomography (PET)/computed tomography (CT) and collection of blood samples throughout the trial. Patients may undergo biopsy at screening.

After completion of study treatment, patients are followed up at days 240, 365, 455, 547, 637, and 730.

Study Type

Interventional

Enrollment (Estimated)

18

Phase

  • Phase 1

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
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Recruiting
        • Ohio State University Comprehensive Cancer Center
        • Contact:
        • Principal Investigator:
          • Nathan Denlinger, DO, MS

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:

  • Written informed consent obtained to participate in the study and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information
  • Age ≥ 18 years at the time of consent
  • Diagnosis of B-cell Non-Hodgkin's lymphoma including either large B-cell lymphoma or follicular lymphoma. Large B-cell subtypes include but are not limited to diffuse large B-cell lymphoma, high grade B-cell lymphoma (except Burkitt's Lymphoma), primary mediastinal B-cell lymphoma, and diffuse large B cell lymphoma transformed from indolent lymphomas
  • Eastern Cooperative Oncology Group (ECOG) Score = 0-2
  • Prior receipt of standard of care CD19 directed CAR-T cell therapy including axicabtagene ciloleucel, tisagenlecleucel, or lisocabtagene maraleucel
  • Pre-CART imaging within 90 days of infusion of CD19.CAR-T for baseline disease evaluation. If patient's receive bridging therapy, imaging evaluation post bridging therapy is encouraged as part of institutional guidelines, but not mandated for inclusion
  • Evidence of objective response on PET/CT at 25-100 days post CD19.CAR-T infusion compared to baseline pre-CART imaging. Objective response in this trial is defined by reduced fludeoxyglucose F-18 (FDG) uptake or reduction in mass size and includes mixed response
  • Evidence of sub-optimal response to CD19.CAR-T as defined in this trial by Deauville Score ≥ 3 on PET/CT at 25-100 days post CD19.CAR-T infusion.
  • Absolute neutrophil count ≥ 7.5 x 10^8/L (obtained within 30 days prior to initiating study treatment)

  • Evidence of partial response, though sub-optimal response as determined by persistent MRD positivity. (Example: Deauville Score 1 or 2 is eligible if MRD is positive via clonoseq).

    • Hematological lab values should be without the use of growth factors or transfusion support
    • Note: Changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy

  • Hemoglobin ≥ 8 x 10^9/L (obtained within 30 days prior to initiating study treatment)

    • Hematological lab values should be without the use of growth factors or transfusion support
    • Note: Changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy

  • Platelets ≥ 50 x 10^9/L (obtained within 30 days prior to initiating study treatment)

    • Hematological lab values should be without the use of growth factors or transfusion support
    • Note: Changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy

  • Estimated glomerular filtration rate (eGFR) (based on chronic kidney disease-epidemiology collaboration [CKD-EPI] * patient's body surface area [BSA] [Du Bois method]/1.73m^2) ≥ 45 ml/min (obtained within 30 days prior to initiating study treatment)

    • Note: Changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy

  • Bilirubin ≤ 1.5 × upper limit of normal (ULN). Subjects with Gilbert's syndrome may be enrolled despite a total bilirubin level > 2.0 mg/dL if their conjugated bilirubin is < 2.0 × ULN) (obtained within 30 days prior to initiating study treatment)

    • Note: Changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy

  • Aspartate aminotransferase (AST) ≤ 3.0 × ULN (obtained within 30 days prior to initiating study treatment)

    • Note: Changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy

  • Alanine aminotransferase (ALT) ≤ 3.0 × ULN (obtained within 30 days prior to initiating study treatment)

    • Note: Changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy
  • Patients must be able to provide adequate tissue samples for minimal residual disease (MRD) analysis for identification (ID) of baseline tumor deoxyribonucleic acid (DNA). 2 forms of tissue will be acceptable: optional baseline biopsy tissue post CART and prior to initiation of CC-99282, or archival tumor tissue (ex. formalin-fixed paraffin embedded [FFPE] tumor blocks) from a biopsy containing lymphoma prior to CD19.CART
  • Fridericia's formula-corrected QT interval (QTcF) < 470 ms
  • Patients must be able to swallow/absorb capsules
  • Females of childbearing potential must have a negative serum pregnancy test within 3 days prior to enrollment. Pregnancy tests must be medically supervised with a minimum sensitivity of 25mIU/ml. NOTE: a female of childbearing potential is a female who: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months, i.e. has had menses at any time in the preceding 24 consecutive months. Documentation of postmenopausal status must be provided. Further information on pregnancy testing and the definition of a female of childbearing potential located in the CC-99282 pregnancy prevention plan document
  • Females of childbearing potential are required to use 2 forms of effective methods of contraception or to agree to practice complete abstinence from the time of informed consent, without interruption, at least 28 days before starting CC-99282, throughout the entire duration of CC-99282, during dose interruptions and for at least 6 months and 2 weeks after the last dose of golcadomide (BMS-986369)/CC-99282. The two contraception methods can be comprised one highly effective method and one additional effective (barrier) method. Further information on acceptable methods is located in the CC-99282 pregnancy prevention plan document
  • Male subjects with female partners must practice complete abstinence or agree to use a condom during sexual contact with a pregnant female or a female of child bearing potential while taking CC-99282, during dose interruptions and for at least 3 months and 2 weeks following the last dose of CC-99282, even if he has undergone a successful vasectomy. Additional information regarding prevention of pregnancy as it pertains to male subjects is contained within the CC-99282 pregnancy prevention plan document
  • Subjects with prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the experimental regimen are eligible for the trial
  • Subject is willing and able to comply with study procedures based on the judgement of the investigator or protocol designee

Exclusion Criteria:

  • Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study and lactating females must agree to not breastfeed while taking study drugs)
  • Uncontrolled concomitant illness including, but not limited to, symptomatic congestive heart failure (New York Heart Association [NYHA] class III or IV), unstable angina pectoris, myocardial infarction within 1 month prior to enrollment, uncontrolled cardiac arrhythmias, uncontrolled seizures, or severe non compensated hypertension (Systolic blood pressure >= 180mmHg or diastolic blood pressure >= 120mmHg)
  • Receipt of CD19.CAR-T for any indication other than that stated within the inclusions criteria

  • Concomitant use of strong CYP3A inhibitors and inducers. Examples include (but are not limited to):

    • CYP3A inhibitors: atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, and telithromycin.
    • CYP3A inducers: carbamazepine, phenytoin, and rifampin. Patients that are able to come off moderate CYP3A inhibitors/inducers will require a washout period of at least 14 days or 5 half-lives, whichever is shorter, prior to the initiation of study treatment
  • Patients who are actively receiving or have received other investigational agents, including herbal supplements, within 2 weeks or 5 half-lives of enrollment

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 (rituximab, CC-99282)
Patients receive rituximab intravenously (IV) on day 1 of each cycle and CC-99282 orally (PO) once daily (QD) on days 1-14 of each cycle. Treatment repeats every 28 days for up to 6 cycles of rituximab and up to 26 cycles of CC-99282 in the absence of disease progression or unacceptable toxicity. Patients also undergo positron emission tomography (PET)/computed tomography (CT) and collection of blood samples throughout the trial. Patients may undergo biopsy at screening.
Procedure: Biospecimen Collection
Undergo blood sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
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
  • Ikgdar
  • Mabtas
  • Rituximab-abbs
Procedure: Biopsy
Undergo biopsy
Other Names:
  • Bx
  • BIOPSY_TYPE
Procedure: Computed Tomography
Undergo PET/CT
Other Names:
  • CT
  • CAT
  • CAT Scan
  • Computed Axial Tomography
  • Computerized Axial Tomography
  • Computerized Tomography
  • CT Scan
  • tomography
  • Computerized axial tomography (procedure)
Procedure: Positron Emission Tomography
Undergo PET/CT
Other Names:
  • Medical Imaging, Positron Emission Tomography
  • PET
  • PET Scan
  • Positron Emission Tomography Scan
  • Positron-Emission Tomography
  • proton magnetic resonance spectroscopic imaging
  • PT
  • Positron emission tomography (procedure)
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of adverse events
Time Frame: At 30 days post completion of enrollment
Will describe frequency and nature of adverse events associated with CC-99282 + rituximab post CD19 chimeric antigen receptor (CAR) -T cell therapy using Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0.
At 30 days post completion of enrollment
Maximum tolerated dose
Time Frame: At 30 days post completion of enrollment
Will use Bayesian Optimal Interval design to define the maximum tolerated dose.
At 30 days post completion of enrollment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Freedom from progression
Time Frame: At 150 days
Will utilize baseline positron emission tomography/computed tomography at 30 days post infusion of CD19.CART compared to day+150 PET post initiation of CC-99282.
At 150 days
Objective response rate
Time Frame: At 60 days and 150 days post initiation of CC-99282
Will be calculated with 95% confidence interval.
At 60 days and 150 days post initiation of CC-99282
Progression free survival
Time Frame: Time from initiation of CC-99282 to clinical progression or death, assessed at 150 days and 2 years post infusion of CD19.CAR-T cell therapy
Will be estimated using the Kaplan-Meier method.
Time from initiation of CC-99282 to clinical progression or death, assessed at 150 days and 2 years post infusion of CD19.CAR-T cell therapy
Overall survival
Time Frame: Time from CD19.CAR-T infusion to date of death as a result of any cause, assessed at 150 days and 2 years post infusion of CD19.CAR-T cell therapy
Will be estimated using the Kaplan-Meier method.
Time from CD19.CAR-T infusion to date of death as a result of any cause, assessed at 150 days and 2 years post infusion of CD19.CAR-T cell therapy
Incidence of adverse events
Time Frame: Up to 2 years
The frequency and nature of adverse events associated with CC-99282 + rituximab post CD19.CAR-T cell therapy will be described using CTCAE v5.0.
Up to 2 years
Number of patients with response to treatment as assessed by PET imaging
Time Frame: At 60 days and 150 days post initiation of CC-99282 and then every 3 months, assessed up to 2 years
Patients with response to treatment assessed by PET imaging and as defined by the Lugano criteria. Lugano classification is a five-point scale for reporting FDG PET.
At 60 days and 150 days post initiation of CC-99282 and then every 3 months, assessed up to 2 years
Number of patients with response to treatment as assessed by CT imaging
Time Frame: At 60 days and 150 days post initiation of CC-99282 and then every 3 months, assessed up to 2 years
Patients with response to treatment assessed by CT imaging and as defined by the Lugano criteria. Lugano classification is a five-point scale for reporting FDG PET.
At 60 days and 150 days post initiation of CC-99282 and then every 3 months, assessed up to 2 years

Collaborators and Investigators

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

Sponsor

Nathan Denlinger

Collaborators

Bristol-Myers Squibb

Investigators

  • Principal Investigator: Nathan Denlinger, DO, MS, Ohio State University Comprehensive Cancer Center

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)

January 29, 2024

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

December 31, 2026

Study Registration Dates

First Submitted

January 8, 2024

First Submitted That Met QC Criteria

January 8, 2024

First Posted (Actual)

January 17, 2024

Study Record Updates

Last Update Posted (Actual)

February 27, 2026

Last Update Submitted That Met QC Criteria

February 24, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • OSU-23214
  • NCI-2023-10172 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

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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