Golcadomide in Combination With Rituximab for the Treatment of Patients With Relapsed or Refractory Mantle Cell Lymphoma

A Phase 1/2 Study of the CELMoD Agent Golcadomide in Combination With Rituximab in Patients With Relapsed or Refractory Mantle Cell Lymphoma

This phase I/II trial tests the safety, side effects, best dose and effectiveness of golcadomide in combination with rituximab in treating patients with mantle cell lymphoma that has come back after a period of improvement (relapsed) or that does not respond to treatment (refractory). 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 in combination with rituximab may better treat patients with relapsed or refractory mantle cell lymphoma.

Study Overview

• Status: Not yet recruiting
• Conditions: Recurrent Mantle Cell Lymphoma; Refractory Mantle Cell Lymphoma
• Intervention / Treatment: Procedure: Biospecimen Collection; Biological: Rituximab; Procedure: Computed Tomography; Procedure: Positron Emission Tomography; Procedure: Bone Marrow Biopsy; Drug: Golcadomide; Procedure: Biopsy Procedure

Detailed Description

PRIMARY OBJECTIVES:

I. To evaluate the safety and tolerance of golcadomide in mantle cell lymphoma (MCL) patients who were resistant or intolerant to covalent bruton's tyrosine kinase inhibitors (cBTKi).

II. To evaluate the safety and tolerance of golcadomide in combination with rituximab in MCL patients who were resistant or intolerant to cBTKi.

III. To estimate the efficacy of golcadomide and rituximab in MCL patients who were resistant or intolerant to cBTKi.

SECONDARY OBJECTIVES:

I. To evaluate the complete response rate (CR) of the combination of golcadomide and rituximab.

II. To evaluate the durability of response by the duration of response (DOR) and duration of complete response (DOCR).

EXPLORATORY OBJECTIVES:

I. Correlate clinical response with changes in baseline T cell characteristics and cytokine profiles.

II. To measure the rate of minimal residual disease undetectability in responding patients.

OUTLINE: This is a phase I, dose-escalation study of golcadomide followed by a phase II study. Patients are assigned to 1 of 2 phases.

PHASE I: Patients receive golcadomide orally (PO) once daily (QD) on days 1-14 of each cycle. Cycles repeat every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection and positron emission tomography (PET)/computed tomography (CT) throughout the trial. Patients undergo bone marrow biopsy and may undergo tissue biopsy on study.

PHASE II: Patients receive golcadomide PO QD on days 1-14 of each cycle. Patients also receive rituximab intravenously (IV) on days 1, 8, 15 and 22 of cycle 1 and then day 1 of even cycles. Cycles repeat every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection and PET/CT throughout the trial. Patients undergo bone marrow biopsy and may undergo tissue biopsy on study.

After completion of study treatment, patients are followed up at 30 days, and then up to 3 years.

• Study Type: Interventional
• Enrollment (Estimated): 58
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope Medical Center
      • Principal Investigator: Tycel J. Phillips
      • Contact: Tycel J. Phillips; Phone Number: 82405 626-256-4673; Email: tphillips@coh.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Documented informed consent of the participant and/or legally authorized representative

• Agreement to allow the use of archival tissue from diagnostic tumor biopsies

  • If unavailable, exceptions may be granted with study principal investigator (PI) approval
• Ability to adhere to the study protocol
• Age: ≥ 18 years
• Eastern Clinical Oncology Group (ECOG) ≤ 2

• Histologically confirmed diagnosis of MCL

  • Immunohistochemistry of the biopsy
  • Flow cytometry of the biopsy
• Relapsed/ refractory disease
• Relapsed/refractory (R/R) MCL after at least one line of therapy including resistant or intolerant to a cBTKi
• Fully recovered from the acute toxic effects (except alopecia) to ≤ grade 1 to prior anti-cancer therapy
• Ability to swallow pills

• Without bone marrow involvement: Absolute neutrophil count (ANC) > 1.5 × 10^9/L (ANC > 1,500/mm^3)

  • With bone marrow involvement: ANC > 1.0 × 10^9/L (ANC > 1000/mm^3)
  • NOTE: Growth factor is not permitted within 14 days of ANC assessment unless cytopenia is secondary to disease involvement. For patients with significant marrow involvement, eligibility may be confirmed at the discretion of the treating investigator

• Without bone marrow involvement: Platelets ≥ 75,000/mm^3

  • With bone marrow involvement: Platelets ≥ 50,000/mm^3
  • NOTE: Platelet transfusions are not permitted within 14 days of platelet assessment unless cytopenia is secondary to disease involvement
• Total bilirubin ≤ 1.5 × upper limit of normal (ULN) (≤ 1.5 × ULN if Gilbert's disease)
• Aspartate aminotransferase (AST) =< 2.5 × ULN
• Alanine aminotransferase (ALT) ≤ 2.5 × ULN unless elevation is attributable to underlying disease, in which case ALT ≤ 3.0 × ULN
• Creatinine clearance of ≥ 30 mL/min per 24 hour urine test or the Cockcroft-Gault formula
• If not receiving anticoagulants: International normalized ratio (INR) OR prothrombin (PT) ≤ 1.5 × ULN. If on anticoagulant therapy: PT must be within therapeutic range of intended use of anticoagulants
• If not receiving anticoagulants: Activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN. If on anticoagulant therapy: aPTT must be within therapeutic range of intended use of anticoagulants
• Seronegative for HIV
• Seronegative for hepatitis C virus (HCV), hepatitis B virus (HBV) (surface antigen negative)

• Meets other institutional and federal requirements for infectious disease titer requirements

  • Note Infectious disease testing to be performed within 28 days prior to day 1 of protocol therapy
• Woman of childbearing potential must have a negative pregnancy test using a highly sensitive assay (minimum sensitivity 25 IU/L) performed within 10 to 14 days and again within 24 hours prior to receiving the first dose of golcadomide/BMS-986369

• Agreement by females of childbearing potential to use two effective methods of contraception simultaneously without interruption, for at least 28 days before starting study treatment, throughout the entire duration of study treatment, during dose interruptions, and for at least 28 days after the last dose of golcadomide/BMS-986369. The two methods of contraception must include one highly effective method and one additional effective method. Compliance will be documented using the Clinical Trial Pregnancy Risk Awareness Checklist, which must be completed and provided to participants at screening and prior to dispensing of study drug. An individual of childbearing potential (IOCBP) is defined as:

  • A person who has achieved menarche, has not undergone a documented hysterectomy or bilateral oophorectomy, and has not been naturally postmenopausal for at least 12 consecutive months. Amenorrhea resulting from medical interventions (such as cancer therapy), rather than natural menopause, does not exclude childbearing potential.

Criteria:

• Achievement of menarche (onset of menstruation).

• No history of surgical sterilization:

  • No documented hysterectomy
  • No documented bilateral oophorectomy

• Not naturally postmenopausal:

  • Defined as absence of menses for ≥ 12 consecutive months due to natural causes (not due to medical interventions such as chemotherapy, hormonal therapy, or radiotherapy)
• Amenorrhea due to medical causes (e.g., cancer therapy, hormonal treatment) does not qualify as natural menopause and does not exclude childbearing potential

Exclusion Criteria:

• Chemotherapy, radiation therapy (except for palliative radiation therapy [XRT]), biological therapy, immunotherapy within 21 days or five half-lives (whichever is shorter for non-radiation therapy) prior to day 1 of protocol therapy
• Strong CYP3A4 inducers/ inhibitors within 14 days prior to day 1 of protocol therapy
• Herbal medications
• History of metastatic cancer

• Unstable cardiac disease as defined by one of the following:

  • Cardiac events such as myocardial infarction (MI) within the past 6 months
  • New York Heart Association (NYHA) heart failure class III-IV
  • Uncontrolled atrial fibrillation or hypertension
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agents
• Clinically significant uncontrolled illness
• Known seropositive or active infection with HIV, HBV, or HCV
• Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment or any major episode of infection (as evaluated by the investigator) within 4 weeks prior to the first study treatment
• Females only: Pregnant or breastfeeding
• Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
• Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase I (Golcadomide); Patients receive golcadomide PO QD on days 1-14 of each cycle. Cycles repeat every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection and PET/CT throughout the trial. Patients undergo bone marrow biopsy and may undergo tissue biopsy on study.	Procedure: Biospecimen Collection; Undergo blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; 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); Computerized Tomography (CT) scan; Diagnostic CAT Scan; Diagnostic CAT Scan Service Type; 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: Bone Marrow Biopsy; Undergo bone marrow 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; Procedure: Biopsy Procedure; Undergo tissue biopsy; Other Names: Bx; BIOPSY_TYPE; Biopsy
Experimental: Phase II (Golcadomide, rituximab); Patients receive golcadomide PO QD on days 1-14 of each cycle. Patients also receive rituximab IV on days 1, 8, 15 and 22 of cycle 1 and then day 1 of even cycles. Cycles repeat every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection and PET/CT throughout the trial. Patients undergo bone marrow biopsy and may undergo tissue biopsy on study.	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; 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: 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); Computerized Tomography (CT) scan; Diagnostic CAT Scan; Diagnostic CAT Scan Service Type; 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: Bone Marrow Biopsy; Undergo bone marrow 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; Procedure: Biopsy Procedure; Undergo tissue biopsy; Other Names: Bx; BIOPSY_TYPE; Biopsy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of dose limiting toxicities (DLT)	The adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI CTCAE v 5.0). Toxicity will be summarized by type, severity, and attribution. DLT will be individually described.	During cycle 1 (Cycle length = 28 days)
Maximum tolerated dose (MTD) of golcadomide	If single agent is tolerable, we will subsequently explore golcadomide in combination with rituximab.	Up to 3 years
MTD of golcadomide in combination with rituximab	Patients would remain on therapy until unacceptable toxicity, treating physician discretion or PD.	Up to 3 years
Overall response rate (ORR)	Defined as achieving a best response of either complete metabolic response (CMR) or partial metabolic response (PMR) in a response-evaluable participant after the start of protocol therapy and prior to disease progression and/or start of other anti-lymphoma therapy. ORR will be estimated by binary proportions, along with the 95% exact binomial confidence intervals.	Up to 3 years
Progression free survival (PFS)	PFS will be estimated using the product-limit method of Kaplan and Meier along with the Greenwood estimator of standard error; 95% confidence interval will be constructed based on log-log transformation.	From start of protocol treatment to time of disease relapse/progression or death due to any cause, whichever occurs earlier, assessed up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events	Will be graded by NCI CTCAE v 5.0. Toxicity will be summarized by type, severity, and attribution.	Up to 3 years
Duration of response (DOR) of the combination of golcadomide and rituximab	DOR will be estimated using the product-limit method of Kaplan and Meier.	From the first achievement of PMR or CMR to time of progressive disease (PD) or death, whichever earlier, assessed up to 3 years
Duration of complete response (DOCR) of the combination of golcadomide and rituximab	DOCR will be estimated using the product-limit method of Kaplan and Meier.	Time from the first achievement of CMR to time of PD or death, whichever earlier, assessed up to 3 years
Complete response (CR) of the combination of golcadomide and rituximab	CR rate will be estimated by binary proportions, along with the 95% exact binomial confidence intervals.	Up to 3 years

Collaborators and Investigators

• Sponsor: City of Hope Medical Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Tycel J Phillips, City of Hope Medical Center

Study record dates

Study Major Dates

• Study Start (Estimated): December 21, 2026
• Primary Completion (Estimated): April 21, 2030
• Study Completion (Estimated): April 21, 2030

Study Registration Dates

• First Submitted: May 5, 2026
• First Submitted That Met QC Criteria: May 5, 2026
• First Posted (Actual): May 11, 2026

Study Record Updates

• Last Update Posted (Actual): May 11, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Hemic and Lymphatic Diseases; Lymphoma, Mantle-Cell; Amino Acids, Peptides, and Proteins; Proteins; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Surgical Procedures, Operative; Cytological Techniques; Cytodiagnosis; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Diagnostic Techniques, Surgical; Chemistry Techniques, Analytical; Spectrum Analysis; Antibodies, Monoclonal, Murine-Derived; Rituximab; Biopsy; Specimen Handling; Magnetic Resonance Spectroscopy; CT-P10
• Other Study ID Numbers: 25448 (Other Identifier: City of Hope Medical Center); P30CA033572 (U.S. NIH Grant/Contract); NCI-2026-02921 (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