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) (FIL_RICCO)

December 31, 2025 updated by: Fondazione Italiana Linfomi - ETS
Prospective, multicenter, single arm, phase II study, to evaluate the efficacy of the combination rituximab-golcadomide as a chemo free approach in a population of older patients with new diagnosis of DLBCL, defined as frail according to a sGA evaluation and not candidate for the standard R-CHOP (or R-CHOP like) treatments.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a prospective, multicenter, phase II study, in older patients affected by DLBCL defined as frail according to sGA and previously untreated.

All patients will receive an induction phase with a combination of golcadomide, rituximab and only at cycle 1 dexamethasone, for a maximum number of 6 cycles of 28 days.

Response assessment is planned after 4 and after 6 cycles for identification of non-responding patients. Patients achieving at least a PR at the interim restaging and after 6th cycle will complete therapy as planned, while patients with stable and progressive disease will discontinue protocol treatment and will be addressed to an alternative regimen.

At the end of the 6th cycle of induction (EOI), involved site radiotherapy is allowed on PET positive sites.

At EOI (end of induction), if the patient reached at least a partial response (≥PR), a consolidation phase was planned with golcadomide, for a maximum of 6 cycles of 28 days.

During consolidation phase, an interim check for response will be performed after the completion of 3 cycles in order to early identify progressive disease. Patients with progressive disease will stop protocol treatment and will be treated at physician discretion.

End of treatment response will be evaluated within 4-6 weeks after the last cycle of consolidation (or the last study medication administration).

All patients will be monitored during follow up for 24 months, every 3 months for the first year and every 6 months for the second year.

Patients experimenting progression at any time will be considered as treatment failures and will be followed-up for survival until the end of the study.

Baseline and EOT 18FDG PET/CT or CT scan including pre-contrast phase (only if PET/CT is not performed) will be evaluated for sarcopenia assessment.

Quality of life (QoL) evaluation is planned at study entry and at established timepoints during and after treatment and follow-up.

Study Type

Interventional

Enrollment (Estimated)

47

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 Contact Backup

Study Locations

  • Italy
      • Alessandria, Italy, 15121
        • Recruiting
        • AOU SS. Antonio e Biagio e Cesare Arrigo di Alessandria - SCDU Ematologia
        • Contact:
        • Principal Investigator:
          • Manuela Zanni, Dr.
      • Ancona, Italy
        • Recruiting
        • AOU Ospedali Riuniti - Clinica di Ematologia
        • Contact:
        • Principal Investigator:
          • Guido Gini, Dr.
      • Avellino, Italy
        • Recruiting
        • Azienda Ospedaliera S. Giuseppe Moscati - S.C. Ematologia e trapianto emopoietico
        • Contact:
        • Principal Investigator:
          • Sonya De Lorenzo, Dr.
      • Aviano, Italy
        • Recruiting
        • Ospedale IRCCS Centro di Riferimento Oncologico di Aviano - Divisione di Oncologia e dei Tumori immuno-correlati
        • Contact:
          • Michele Spina, Dr.
          • Phone Number: +390434659730
          • Email: mspina@cro.it
        • Principal Investigator:
          • Michele Spina, Dr.
      • Brescia, Italy
        • Recruiting
        • ASST Spedali Civili di Brescia - Ematologia
        • Contact:
        • Principal Investigator:
          • Alessandra Tucci, Dr.
      • Florence, Italy
        • Recruiting
        • Azienda Ospedaliera Universitaria Careggi -Unità Funzionale di Ematologia
        • Contact:
        • Principal Investigator:
          • Benedetta Puccini, Dr.
      • Milan, Italy
        • Recruiting
        • ASST Grande Ospedale Metropolitano Niguarda - SC Ematologia
        • Contact:
        • Principal Investigator:
          • Vittorio Zilioli, Dr.
      • Monza, Italy
        • Recruiting
        • Fondazione IRCCS San Gerardo dei Tintori -Ematologia
        • Contact:
        • Principal Investigator:
          • Ivana Casaroli, Dr.
      • Padua, Italy
        • Recruiting
        • I.R.C.C.S. Istituto Oncologico Veneto -Oncologia 1
        • Contact:
        • Principal Investigator:
          • Dario Marino, Dr.
      • Palermo, Italy
        • Not yet recruiting
        • Policlinico Giaccone - Ematologia
        • Contact:
        • Principal Investigator:
          • Salvatrice Mancuso, Dr.
      • Pescara, Italy, 65128
        • Not yet recruiting
        • Azienda Sanitaria Locale di Pescara- Presidio Ospedaliero Santo Spirito - U.O.C. Ematologia
        • Principal Investigator:
          • Elsa Pennese, MD
        • Contact:
      • Piacenza, Italy
        • Recruiting
        • Azienda USL Piacenza - UOC Ematologia e Centro Trapianti,
        • Contact:
        • Principal Investigator:
          • Annalisa Arcari, Dr.
      • Ravenna, Italy
        • Recruiting
        • Ospedale delle Croci - Ematologia
        • Principal Investigator:
          • Monica Tani, Dr.
        • Contact:
      • Reggio Emilia, Italy
        • Recruiting
        • Azienda Unità Sanitaria Locale-IRCCS - Arcispedale Santa Maria Nuova - Ematologia
        • Contact:
        • Principal Investigator:
          • Maria Elena Nizzoli, Dr.
      • Roma, Italy
        • Recruiting
        • Ematologia - Trapianto cellule staminali - Medicina Trasfusionale e Terapie Cellulari, Policlinico Universitario Campus Bio-Medico
        • Principal Investigator:
          • Luigi Rigacci, Dr.
        • Contact:
      • Siena, Italy
        • Not yet recruiting
        • AOU Senese - U.O.C. Ematologia
        • Contact:
        • Principal Investigator:
          • Alberto Fabbri, Dr.
      • Torino, Italy
        • Recruiting
        • A.O.U. Citta della Salute e della Scienza di Torino - Ematologia Universitaria
        • Principal Investigator:
          • Federica Cavallo, Dr.
        • Contact:
      • Torino, Italy
        • Recruiting
        • A.O.U. Città della Salute e della Scienza di Torino - S.C. Ematologia
        • Contact:
        • Principal Investigator:
          • Mattia Novo, Dr.
      • Trieste, Italy
        • Recruiting
        • Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI) - S.C. Ematologia
        • Contact:
        • Principal Investigator:
          • Elisa Lucchini, Dr.
      • Verona, Italy
        • Recruiting
        • AOU Integrata di Verona - U.O. Ematologia
        • Contact:
        • Principal Investigator:
          • Cinzia Sissa, Dr.

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

  • Older Adult

Accepts Healthy Volunteers

No

Description

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

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: Rituximab in combination with Golcadomide (CC-99282)

Induction Phase (6 cycles every 28 days): Cycle 1 (Rituximab 375 mg/mq i.v. on days 1, 8, 15; Golcadomide 0,3 mg/day p.o. days 1-14; Dexamethasone 5 mg p.o. on days 1, 8, 15, 22). Cycles 2-6 (Rituximab 375 mg/mq i.v. on day 1; Golcadomide 0,4 mg/day p.o. days 1-14).

Consolidation phase (for patients achieving at least a partial response at the end of induction (≥PR), the consolidation phase will start within 6-8 weeks from Cycle 6 Day1 and will be continued up to 6 cycles every 28 days): golcadomide 0.2 mg / day p.o. days 1-14.

Consolidation radiotherapy: involved site radiotherapy (ISR) is allowed at the end of induction phase on PET positive sites, according to the available guidelines (Illidge et al., 2014). ISR should be concomitant to consolidation phase.
Drug: Rituximab + Golcadomide (CC-99282)
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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression free survival (PFS) at 24 months
Time Frame: from enrollment to 24 month
PFS defined as the time between the start of prephase and the first documentation of recurrence, progression or death from any cause.
from enrollment to 24 month

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
ORR Overall response rate (partial response, PR + complete response, CR) and CR after the 4th and 6th cycle
Time Frame: From the start of treatment to approximately 4 months and 6 months
ORR Overall response rate (partial response, PR + complete response, CR) and CR after the 4th and 6th cycle
From the start of treatment to approximately 4 months and 6 months
Overall survival (OS)
Time Frame: from enrollment to 60 month
OS defined as the time between the start of prephase and death from any cause
from enrollment to 60 month
Rate of treatment discontinuation due to AE or treatment intolerance
Time Frame: From the start of treatment to 60 months
Rate of treatment discontinuation due to AE or treatment intolerance
From the start of treatment to 60 months
QoL (quality of life) scores at baseline - EORTC-QLQ-C30
Time Frame: The endpoint wil be evaluated at the baseline
Quality of life is measured with the EORTC-QLQ-C30 (European Organisation for Research and Treatment of Cancer-Quality of life Questionnaire-Core 30) questionnaire
The endpoint wil be evaluated at the baseline
QoL (quality of life) scores variations at 6 months - EORTC-QLQ-C30
Time Frame: The endpoint will be evaluated from the beginning of the study to 6 months
Quality of life is measured with the EORTC-QLQ-C30 (European Organisation for Research and Treatment of Cancer-Quality of life Questionnaire-Core 30) questionnaire
The endpoint will be evaluated from the beginning of the study to 6 months
QoL (quality of life) scores variations at 12 months - EORTC-QLQ-C30
Time Frame: The endpoint will be evaluated from the beginning of the study to 12 months
Quality of life is measured with the EORTC-QLQ-C30 (European Organisation for Research and Treatment of Cancer-Quality of life Questionnaire-Core 30) questionnaire
The endpoint will be evaluated from the beginning of the study to 12 months
QoL (quality of life) scores at baseline - FACT-Lym-LymS
Time Frame: The endpoint wil be evaluated at the baseline
Quality of life is measured with the FACT-Lym-LymS (Functional Assessment of Cancer Therapy - Lymphoma- lymphoma-specific symptoms)
The endpoint wil be evaluated at the baseline
QoL (quality of life) scores variations at 6 months - FACT-Lym-LymS
Time Frame: The endpoint will be evaluated from the beginning of the study to 6 months
Quality of life is measured with the FACT-Lym-LymS (Functional Assessment of Cancer Therapy - Lymphoma- lymphoma-specific symptoms questionnaire)
The endpoint will be evaluated from the beginning of the study to 6 months
QoL (quality of life) scores variations after 12 months - FACT-Lym-LymS
Time Frame: The endpoint will be evaluated from the beginning of the study to 12 months
Quality of life is measured with the FACT-Lym-LymS (Functional Assessment of Cancer Therapy - Lymphoma- lymphoma-specific symptoms)
The endpoint will be evaluated from the beginning of the study to 12 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Difference of sarcopenia degree before and after treatment according to European Working Group on Sarcopenia in Older People (EWGSOP2)
Time Frame: from enrollment to 60 month
To assess sarcopenia at study entry and after treatment
from enrollment to 60 month

Collaborators and Investigators

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

Sponsor

Fondazione Italiana Linfomi - ETS

Investigators

  • Principal Investigator: Alessandra Tucci, Dr.ssa, UO Ematologia, ASST Spedali Civili di Brescia, Piazzale Spedali Civili, 1, 25123 Brescia, Italia

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 9, 2025

Primary Completion (Estimated)

April 1, 2030

Study Completion (Estimated)

April 1, 2030

Study Registration Dates

First Submitted

February 10, 2025

First Submitted That Met QC Criteria

February 17, 2025

First Posted (Actual)

February 19, 2025

Study Record Updates

Last Update Posted (Estimated)

January 2, 2026

Last Update Submitted That Met QC Criteria

December 31, 2025

Last Verified

December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FIL_RICCO
  • 2023-506206-38-00 (Ctis)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

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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