Study carried out at multiple centers to test Glofitamab in patients with mantle cell lymphoma who did not respond well to, or relapsed after, CAR T-cell therapy.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondazione Italiana Linfomi Ets

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

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

Decision date (initial)

2026-04-14

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Roche S.p.A.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

To assess the activity of glofitamab treatment in post CAR-T R/R MCL patients

Secondary objectives 2

1. To assess the clinical outcome after glofitamab treatment in post CAR-T R/R MCL patients
2. To assess the safety profile of glofitamab treatment in post CAR-T R/R MCL patients

Conditions and MedDRA coding

Mantle Cell Lymphoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. Able to provide written informed consent forms 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. Adequate hepatic function per local laboratory reference range as follows (unless due to lymphoma): - Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 x ULN; - Bilirubin ≤1.5 x ULN (unless bilirubin rise is due to Gilbert’s syndrome or of non-hepatic origin).
3. Participants must be able to adhere to the study visit schedule and other protocol requirements.
4. Life expectancy > 12 weeks.
5. ECOG Performance Status of 0, 1, or 2.
6. Women of childbearing potential must have a negative pregnancy test at screening.
7. Women of childbearing potential must take necessary precautions to avoid pregnancy while receiving study treatments and for 2 months after the last dose of glofitamab, for 18 months after the last dose of obinutuzumab and for 3 months after the last dose of tocilizumab.
8. Male patient with a female partner of childbearing potential must agree to use an acceptable method of contraception for the duration of the study and for 2 months after the last dose of glofitamab, for 3 months after the last dose of obinutuzumab and for 2 months after the last dose of tocilizumab.
9. Histologically confirmed MCL after CAR T-cells failure (CD20+ by flow cytometry or immunohistochemistry). Note: Availability of archival material is mandatory for the study to perform central pathology review. Central pathology confirmation is not required to start treatment.
10. Age ≥ 18
11. Patients who received CAR T-cells therapy for R/R MCL at least 30 days prior to signing the informed consent form and who meet one of the following situations: - Stable disease (SD) or progressive disease (PD) up to D+90; after CAR T-cells infusion (from D+30 to D+90); - Partial response (PR) at D+90 after CAR-T cells infusion; - Relapsed disease at any time after CAR-T cells infusion.
12. No persistent CAR-T neurotoxicity symptoms or previous experience during CAR T-cells therapy of severe neurotoxicity grade > 3
13. Adverse events from prior anti-cancer therapy must have resolved to Grade ≤ 1 (hematological toxicities excepted).
14. Adequate hematological counts are defined as follows: - Absolute neutrophil count (ANC) > 1.0 x 109/L unless due to bone marrow involvement by lymphoma; - Platelet count ≥ 50.000/mm3 unless due to bone marrow involvement by lymphoma; - Hemoglobin ≥ 8.0 g/dL.
15. Adequate renal function defined as follows: - Creatinine clearance ≥ 30 mL/min (Cockcroft–Gault formula).

Exclusion criteria 14

1. Prior exposure to an anti-CD20xCD3 bispecific antibody (bsAbs).
2. Participant has received any anti-cancer therapy including chemotherapy, immunotherapy, radiotherapy, investigational therapy, including targeted small molecule agents within 14 days prior to the first dose of study drug.
3. Cardiovascular disease [NYHA class ≥2]
4. Significant history of neurologic, psychiatric, endocrinological, metabolic, immunologic, or hepatic disease that would preclude participation in the study or compromise ability to give informed consent.
5. Evidence of other clinically significant uncontrolled condition(s) included, 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) require treatment. Note: participants 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) or positive anti-HBc antibody from previous infection or intravenous immunoglobulins (IVIG) may participate; inactive carriers (HBsAg positive with undetectable HBV- DNA) are eligible. Patients with presence of HCV antibody are eligible only if PCR negative for HCV-RNA
6. HIV seropositivity.
7. If female, the patient is pregnant or breast-feeding.
8. Participants not able to give consent.
9. History of treatment-emergent immune-related adverse events associated with prior immunotherapeutic agents, as follows: - Grade ≥ 3 adverse events except for Grade 3 endocrinopathy managed with replacement therapy; - Grade 1-2 adverse events that did not resolve to baseline after treatment discontinuation.
10. Patients with history of macrophage activation syndrome (MAS) / hemophagocytic lymphohistiocytosis (HLH).
11. Allogeneic hematopoietic stem cell transplantation.
12. History of progressive multifocal leukoencephalopathy (PML).
13. History of autoimmune disease, including, but not limited to myocarditis, pneumonitis, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.
14. CNS involvement with lymphoma.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Complete Response Rate (CRR) at any time during study treatment (assessed by the independent review committee according to Lugano 2014 criteria)

Secondary endpoints 8

1. Overall Response Rate (ORR) defined as the proportion of patients achieving either a Complete Response (CR) or Partial Response (PR) (assessed by the independent review committee according to Lugano 2014 criteria), and evaluated at C6 and C12
2. Complete Response Rate (CRR) at the end of treatment (C12) (assessed by the independent review committee according to Lugano 2014 criteria)
3. Progression Free Survival (PFS) defined as the time from the study inclusion to disease progression or death from any cause
4. Overall Survival (OS) defined as the time between the study inclusion and death from any cause
5. Duration of Response (DOR) defined as the time from the first documentation of tumor response (Complete or Partial Response) to disease progression or death
6. Time to Next Treatment (TTNT) defined as the time represents the interval from the study inclusion to initiation of the next line of therapy.
7. Event Free Survival (EFS) defined as the time from the study inclusion to disease progression, death, or Next Anti-Lymphoma Treatment (NALT) start.
8. Frequency and severity of adverse events (AEs) classified as per CTCAE latest version and SAE

Investigational products

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

Test 3

Auxiliary 1

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

Marco Ladetto Prof

Public contact point

Organisation

Fondazione Italiana Linfomi Ets

Contact name

Uffici studi FIL (Start up office)

Locations

1 EU/EEA country · 14 investigational sites

By country

Investigational sites

Results and documents

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

Documents 9 files

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

Application history

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