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Rituximab plus golcadomide as a chemo-free first-line option for older frail diffuse large B‑cell lymphoma patients using a simplified geriatric assessment

A Combination of Rituximab and CC-99282 as Front-line Therapy for Older Frail Patients With Diffuse Large B-cells Non-Hodgkin Lymphoma Evaluated With a Simplified Geriatric Assessment (sGA): a Phase II Study of the Fondazione Italiana Linfomi (FIL)

Phase 2 Interventional Fondazione Italiana Linfomi - ETS · NCT06835530

This treatment tests whether combining rituximab and golcadomide can be an effective chemo-free first-line option for older, frail people newly diagnosed with diffuse large B‑cell lymphoma.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment47 (estimated)
Ages80 Years and up
SexAll
SponsorFondazione Italiana Linfomi - ETS Academic / other
Drugs / interventionschemotherapy, rituximab
Locations20 sites (Alessandria and 19 other locations)
Trial IDNCT06835530 on ClinicalTrials.gov

What this trial studies

This is a prospective, multicenter, single-arm Phase II trial enrolling previously untreated older patients with DLBCL who are classified as frail by a simplified geriatric assessment and are not candidates for anthracycline-based therapy. All patients receive up to six 28-day induction cycles of golcadomide plus rituximab (with dexamethasone only in cycle 1), with response checks after cycle 4 and cycle 6. Patients achieving at least a partial response enter a consolidation phase of golcadomide for up to six additional cycles, while non-responders stop protocol therapy and are offered alternative regimens; involved-site radiotherapy is allowed for PET-positive sites after induction. Patients are followed for 24 months with regular visits every three to six months.

Who should consider this trial

Good fit: Ideal candidates are previously untreated DLBCL patients who are judged frail by the simplified geriatric assessment and are not eligible for anthracycline-based (R‑CHOP) regimens.

Not a fit: Patients who are fit for standard R‑CHOP or other anthracycline-based therapies, younger non-frail patients, or those with disease that progresses on this regimen are unlikely to benefit from this approach.

Why it matters

Potential benefit: If successful, this regimen could provide an effective chemo-free first-line alternative with potentially lower toxicity for older, frail DLBCL patients who cannot tolerate standard anthracycline-based chemoimmunotherapy.

How similar studies have performed: Other chemo-free combinations pairing anti‑CD20 antibodies with immunomodulatory or CELMoD agents (for example lenalidomide‑rituximab) have shown activity in B‑cell lymphomas, but golcadomide (CC‑99282) is a newer CELMoD with limited published clinical data in this setting.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

1. Able to provide written informed consent form approved by the National Ethics Committee (NEC) prior to the initiation of any screening or study- specific procedures and able to understand and to comply with the requirements of the study and the schedule of assessments.
2. Histologically documented diagnosis of DLBCL as defined in the 5th edition of the World Health Organization (WHO) classification (2022)
3. Previously untreated
4. Frail patients defined as follows (Appendix A-D): Age ≥ 80 years: activity of daily living (ADL) \< 6 residual functions and/or Instrumental activity of daily living (IADL) \< 8 residual functions and/or cumulative illness rating scale (CIRS) \> 5 comorbidities of grade 2 and/or one or more comorbidities of grade 3-4
5. Patient not eligible to anthracycline-based chemotherapy
6. Ann Arbor Stage I - IV (Appendix E)
7. Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 3 (Appendix F)
8. At least one site of measurable nodal disease at baseline \[≥ 1.5 cm\] in the longest transverse diameter as determined by CT scan
9. Adequate hematological counts defined as follows:

   * WBC \> 2.5 x 109/L with ANC \> 1.0 x 109/L unless due to bone marrow involvement by lymphoma
   * Platelet count ≥ 75 x 109/L unless due to bone marrow involvement by lymphoma
   * Hemoglobin ≥ 10 g/dL unless anemia related to active lymphoma
10. Adequate renal function defined as creatinine clearance ≥ 30 mL/min (Appendix G). The same CrCl cutoff applies in case of documented renal involvement by lymphoma
11. Adequate hepatic function per local laboratory reference range, unless secondary to lymphoma, as follows:

    * Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.0 x ULN
    * Bilirubin ≤ 2 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin, i.e. mild and chronic hemolysis)
12. Subject must be able to adhere to the study visit schedule and other protocol requirements
13. Subject must be able to swallow capsules or tablets
14. Life expectancy ≥ 3 months
15. Male subjects must practice complete abstinence when this is in line with the usual lifestyle (periodic abstinence is not permitted) or agree to use specified contraceptive methods (barrier contraception: condom) during sexual contact with a female of childbearing potential while participating in the study, for at least 28 days following investigational product discontinuation, even if he has undergone a successful vasectomy. Furthermore, they do not have to donate sperm during the study and for at least 28 days after receiving the last dose of study drug. If applicable, male subjects must receive study specific Pregnancy Prevention Plan (PPP).

Exclusion Criteria:

1. Histological diagnosis different from DLBCL
2. Central nervous system (CNS) involvement with lymphoma
3. Severe heart failure (NYHA grado III-IV and/or LVEF \< 45%), liver disease Child Pugh C, history of interstitial lung disease, non-infectious pneumonitis, pulmonary fibrosis, or pulse oximetry of \< 92% while breathing room air, or any other clinical condition that would preclude participation in the study or compromise ability to give informed consent
4. Any history of other active malignancies within 5 years prior to study entry, except for adequately treated in situ carcinoma of the cervix uterine, basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin, previous malignancy confined and surgically resected with curative intent
5. Gastrointestinal dysfunction that may affect drug absorption (eg, gastric bypass surgery, gastrectomy) or any other malabsorption condition
6. Evidence of other clinically significant uncontrolled condition(s) including, but not limited to:

   1. Uncontrolled and/or active systemic infection (viral, bacterial or fungal), including active ongoing infection from SARS-CoV-2
   2. Chronic or acute hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment. Note: subjects with serologic evidence of prior vaccination to HBV i.e. hepatitis B surface (HBs) antigen (Ag) negative, anti-HBs antibody positive and anti-hepatitis B core (HBc) antibody negative, may participate; patients with positive anti-HBc antibody from previous infection or inactive carriers are eligible only with HBV-DNA negative and with concomitant treatment with Lamivudine or Tenofovir
   3. Patients with presence of HCV antibody are eligible only if PCR negative for HCV-RNA
7. Human immunodeficiency virus (HIV) seropositivity
8. Absence of caregivers in non-autonomous patients
9. Allergy or intolerance to the active or inactive ingredients of study drugs

Where this trial is running

Alessandria and 19 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Diffuse Large B Cell Non-Hodgkin Lymphomadiffuse large B-cell non-Hodgkin lymphomasimplified geriatric assessmentrituximabolder frail patientsGolcadomide
Last reviewed 2026-06-10 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.