Clinical trial with a combination of Rituximab and Golcadomide as first line therapy for older frail patients with Diffuse Large B-cells non-Hodgkin Lymphoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondazione Italiana Linfomi Ets

Participant type

Patients

Age range

65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

9 Apr 2025 → ongoing

Decision date (initial)

2025-02-11

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Bristol-Myers Squibb International Corporation

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

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.

Secondary objectives 4

1. To evaluate the activity in terms of response rate
2. To evaluate the efficacy in terms of survival
3. To evaluate the rate of grade 3-4 hematological and extra-hematological adverse events [National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) latest version] and of death for any cause during the treatment
4. To evaluate the QoL according to the chemo free approach

Conditions and MedDRA coding

Diffuse Large B-cells non-Hodgkin Lymphoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

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 10^9/L with ANC > 1.0 x 10^9/L unless due to bone marrow involvement by lymphoma; Platelet count ≥ 75 x 10^9/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)
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 or agree to use specified contraceptive methods 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 7

1. Histological diagnosis different from DLBCL
2. Central nervous system (CNS) involvement with lymphoma
3. Significant history of cardiac, neurologic, psychiatric, endocrinological, metabolic, immunologic, or hepatic disease 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. Evidence of other clinically significant uncontrolled condition(s) including, but not limited to: a. Uncontrolled and/or active systemic infection (viral, bacterial or fungal), including active ongoing infection from SARS-CoV-2; b. 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; c. Patients with presence of HCV antibody are eligible only if PCR negative for HCV-RNA
6. Human immunodeficiency virus (HIV) seropositivity
7. Absence of caregivers in non-autonomous patients

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression free survival (PFS)

Secondary endpoints 4

1. Overall response rate (partial response, PR + complete response, CR) after the 6th cycle
2. Overall survival (OS)
3. Rate of treatment discontinuation due to AE or treatment intolerance
4. Change in QoL assessment from baseline at 6 months and 12 months by EORTC QLQ C-30 and FACT-Lym questionnaires

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondazione Italiana Linfomi Ets

Sponsor organisation

Fondazione Italiana Linfomi Ets

Address

Piazza Filippo Turati 5

City

Alexandria

Postcode

15121

Country

Italy

Scientific contact point

Organisation

Fondazione Italiana Linfomi Ets

Contact name

Dott.ssa Alessandra Tucci

Public contact point

Organisation

Fondazione Italiana Linfomi Ets

Contact name

Start Up office

Locations

1 EU/EEA country · 20 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 15 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications