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)

NCT06835530 | Recruiting Phase 2 DMC

• 2 other identifiers: FIL_RICCO2023-506206-38-00
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 20

Brief Summary

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.

Conditions

Diffuse Large B Cell Non-Hodgkin Lymphoma

Keywords

diffuse large B-cell non-Hodgkin lymphoma; simplified geriatric assessment (sGA); rituximab; older frail patients; Golcadomide

Outcome Measures

Primary Outcomes (1)

• Progression free survival (PFS) at 24 months

  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 Outcomes (9)

• 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)

  from enrollment to 60 month

• 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

  The endpoint wil be evaluated at the baseline

• QoL (quality of life) scores variations at 6 months - EORTC-QLQ-C30

  The endpoint will be evaluated from the beginning of the study to 6 months

Other Outcomes (1)

• Difference of sarcopenia degree before and after treatment according to European Working Group on Sarcopenia in Older People (EWGSOP2)

  from enrollment to 60 month

Study Arms (1)

Rituximab in combination with Golcadomide (CC-99282)

EXPERIMENTAL

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)

Interventions

Rituximab + Golcadomide (CC-99282) DRUG

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).

Rituximab in combination with Golcadomide (CC-99282)

Eligibility Criteria

• Age: 80 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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.
• Histologically documented diagnosis of DLBCL as defined in the 5th edition of the World Health Organization (WHO) classification (2022)
• Previously untreated
• 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
• Patient not eligible to anthracycline-based chemotherapy
• Ann Arbor Stage I - IV (Appendix E)
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 3 (Appendix F)
• At least one site of measurable nodal disease at baseline \[≥ 1.5 cm\] in the longest transverse diameter as determined by CT scan
• 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
• 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
• 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

You may not qualify if:

• Histological diagnosis different from DLBCL
• Central nervous system (CNS) involvement with lymphoma
• 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
• 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
• Gastrointestinal dysfunction that may affect drug absorption (eg, gastric bypass surgery, gastrectomy) or any other malabsorption condition
• Evidence of other clinically significant uncontrolled condition(s) including, but not limited to:
• Uncontrolled and/or active systemic infection (viral, bacterial or fungal), including active ongoing infection from SARS-CoV-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
• Patients with presence of HCV antibody are eligible only if PCR negative for HCV-RNA
• Human immunodeficiency virus (HIV) seropositivity
• Absence of caregivers in non-autonomous patients
• Allergy or intolerance to the active or inactive ingredients of study drugs

Sponsors & Collaborators

• Fondazione Italiana Linfomi - ETS: lead

Study Sites (20)

AOU SS. Antonio e Biagio e Cesare Arrigo di Alessandria - SCDU Ematologia

Alessandria, 15121, Italy

RECRUITING

AOU Ospedali Riuniti - Clinica di Ematologia

Ancona, Italy

RECRUITING

Azienda Ospedaliera S. Giuseppe Moscati - S.C. Ematologia e trapianto emopoietico

Avellino, Italy

RECRUITING

Ospedale IRCCS Centro di Riferimento Oncologico di Aviano - Divisione di Oncologia e dei Tumori immuno-correlati

Aviano, Italy

RECRUITING

ASST Spedali Civili di Brescia - Ematologia

Brescia, Italy

RECRUITING

Azienda Ospedaliera Universitaria Careggi -Unità Funzionale di Ematologia

Florence, Italy

RECRUITING

ASST Grande Ospedale Metropolitano Niguarda - SC Ematologia

Milan, Italy

RECRUITING

Fondazione IRCCS San Gerardo dei Tintori -Ematologia

Monza, Italy

RECRUITING

I.R.C.C.S. Istituto Oncologico Veneto -Oncologia 1

Padua, Italy

RECRUITING

Policlinico Giaccone - Ematologia

Palermo, Italy

NOT YET RECRUITING

Azienda Sanitaria Locale di Pescara- Presidio Ospedaliero Santo Spirito - U.O.C. Ematologia

Pescara, 65128, Italy

NOT YET RECRUITING

Azienda USL Piacenza - UOC Ematologia e Centro Trapianti,

Piacenza, Italy

RECRUITING

Ospedale delle Croci - Ematologia

Ravenna, Italy

RECRUITING

Azienda Unità Sanitaria Locale-IRCCS - Arcispedale Santa Maria Nuova - Ematologia

Reggio Emilia, Italy

RECRUITING

Ematologia - Trapianto cellule staminali - Medicina Trasfusionale e Terapie Cellulari, Policlinico Universitario Campus Bio-Medico

Roma, Italy

RECRUITING

AOU Senese - U.O.C. Ematologia

Siena, Italy

NOT YET RECRUITING

A.O.U. Città della Salute e della Scienza di Torino - Ematologia Universitaria

Torino, Italy

RECRUITING

A.O.U. Città della Salute e della Scienza di Torino - S.C. Ematologia

Torino, Italy

RECRUITING

Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI) - S.C. Ematologia

Trieste, Italy

RECRUITING

AOU Integrata di Verona - U.O. Ematologia

Verona, Italy

RECRUITING

MeSH Terms

Interventions

Rituximab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Alessandra Tucci, Dr.ssa

  UO Ematologia, ASST Spedali Civili di Brescia, Piazzale Spedali Civili, 1, 25123 Brescia, Italia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Uffici Studi FIL

CONTACT

+390131033153; startup@filinf.it

Uffici Studi FIL

CONTACT

+390599769913; gestionestudi@filinf.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2025
• First Posted: February 19, 2025
• Study Start: April 9, 2025
• Primary Completion (Estimated): April 1, 2030
• Study Completion (Estimated): April 1, 2030
• Last Updated: January 2, 2026

Record last verified: 2025-12

Locations

IT (20)