Clinical trial NCT06835530: 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)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
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
Lead sponsor: Fondazione Italiana Linfomi - ETS
Sponsor class: OTHER
First posted: 2025-02-19
Enrollment: 47
Sex: ALL
Minimum age (years): 80
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Progression free survival (PFS) at 24 months
timeFrame: from enrollment to 24 month
Secondary outcomes:
measure: ORR Overall response rate (partial response, PR + complete response, CR) and CR after the 4th and 6th cycle
timeFrame: From the start of treatment to approximately 4 months and 6 months
measure: Overall survival (OS)
timeFrame: from enrollment to 60 month
measure: Rate of treatment discontinuation due to AE or treatment intolerance
timeFrame: From the start of treatment to 60 months
measure: QoL (quality of life) scores at baseline - EORTC-QLQ-C30
timeFrame: The endpoint wil be evaluated at the baseline
measure: QoL (quality of life) scores variations at 6 months - EORTC-QLQ-C30
timeFrame: The endpoint will be evaluated from the beginning of the study to 6 months
measure: QoL (quality of life) scores variations at 12 months - EORTC-QLQ-C30
timeFrame: The endpoint will be evaluated from the beginning of the study to 12 months
measure: QoL (quality of life) scores at baseline - FACT-Lym-LymS
timeFrame: The endpoint wil be evaluated at the baseline
measure: QoL (quality of life) scores variations at 6 months - FACT-Lym-LymS
timeFrame: The endpoint will be evaluated from the beginning of the study to 6 months
measure: QoL (quality of life) scores variations after 12 months - FACT-Lym-LymS
timeFrame: The endpoint will be evaluated from the beginning of the study to 12 months
Other outcomes:
measure: Difference of sarcopenia degree before and after treatment according to European Working Group on Sarcopenia in Older People (EWGSOP2)
timeFrame: from enrollment to 60 month
Locations:
city: Alessandria
country: Italy
facility: AOU SS. Antonio e Biagio e Cesare Arrigo di Alessandria - SCDU Ematologia
city: Ancona
country: Italy
facility: AOU Ospedali Riuniti - Clinica di Ematologia
city: Avellino
country: Italy
facility: Azienda Ospedaliera S. Giuseppe Moscati - S.C. Ematologia e trapianto emopoietico
city: Aviano
country: Italy
facility: Ospedale IRCCS Centro di Riferimento Oncologico di Aviano - Divisione di Oncologia e dei Tumori immuno-correlati
city: Brescia
country: Italy
facility: ASST Spedali Civili di Brescia - Ematologia
city: Firenze
country: Italy
facility: Azienda Ospedaliera Universitaria Careggi -Unità Funzionale di Ematologia
city: Milano
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda - SC Ematologia
city: Monza
country: Italy
facility: Fondazione IRCCS San Gerardo dei Tintori -Ematologia
city: Padova
country: Italy
facility: I.R.C.C.S. Istituto Oncologico Veneto -Oncologia 1
city: Palermo
country: Italy
facility: Policlinico Giaccone - Ematologia
city: Piacenza
country: Italy
facility: Azienda USL Piacenza - UOC Ematologia e Centro Trapianti,
city: Ravenna
country: Italy
facility: Ospedale delle Croci - Ematologia
city: Reggio Emilia
country: Italy
facility: Azienda Unità Sanitaria Locale-IRCCS - Arcispedale Santa Maria Nuova - Ematologia
city: Roma
country: Italy
facility: Ematologia - Trapianto cellule staminali - Medicina Trasfusionale e Terapie Cellulari, Policlinico Universitario Campus Bio-Medico
city: Siena
country: Italy
facility: AOU Senese - U.O.C. Ematologia
city: Torino
country: Italy
facility: A.O.U. Città della Salute e della Scienza di Torino - Ematologia Universitaria
city: Torino
country: Italy
facility: A.O.U. Città della Salute e della Scienza di Torino - S.C. Ematologia
city: Trieste
country: Italy
facility: Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI) - S.C. Ematologia
city: Verona
country: Italy
facility: AOU Integrata di Verona - U.O. Ematologia
Study officials:
affiliation: UO Ematologia, ASST Spedali Civili di Brescia, Piazzale Spedali Civili, 1, 25123 Brescia, Italia
name: Alessandra Tucci, Dr.ssa
role: PRINCIPAL_INVESTIGATOR
References: