Rituximab, bendamustine and cytarabine followed by venetoclax (V-RBAC) in high-risk elderly patients with mantle cell lymphoma (MCL)

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]

Trial duration

3 Sep 2018 → 15 Oct 2025

Decision date (initial)

2024-09-02

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

AbbVie s.r.l.

External identifiers

EU CT number

2024-511533-35-00

EudraCT number

2017-004628-31

ClinicalTrials.gov

NCT03567876

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

To evaluate whether the addition of venetoclax after R-BAC to HR patients with MCL, as defined above, improves the results of the standard R-BAC, in terms of PFS.

Conditions and MedDRA coding

Mantle Cell Lymphoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Previously untreated patients with MCL aged ≥65 years if they are FIT according to the geriatric CGA assessment.
2. age ≤64 years not eliglible to high-dose chemotherapy plus transplantation at physician's judgement (details for non eligibility to be recorded by means of the CIRS, Cumulative Illness rating Scale).
3. Measurable nodal or extranodal disease ≥ 1.5 cm in longest diameter, and measurable in 2 perpendicular dimensions.
4. ECOG performance status ≤2.
5. Positivity for cyclin D1 and/or SOX11 [the latter being mandatory in cases lacking cyclin D1- or t(11;14)-negative].
6. Adequate renal function (Creatinine clearance >50 mL/min), with preserved diuresis
7. Adequate liver function: alanine aminotransferase (ALT)/aspartate aminotransferase (AST) <2.5 x upper limit of normal (ULN) value, total bilirubin <1.5 x ULN, unless directly attributable to the patient’s tumor or to congenital causes.
8. Hepatitis B core antibody (HBcAb) positive/HBsAg negative/HBV-DNA negative patients may be enrolled if correct antiviral prophylaxis is administered at least 2 weeks before initiating protocol treatment.
9. Written informed consent

Exclusion criteria 18

1. Human immunodeficiency virus (HIV) positive.
2. Previous treatment for lymphoma
3. Disease confined to the bone marrow/peripheral blood/spleen, without any other nodal or extranodal involvement
4. In-situ MCL.
5. Medical conditions or organ injuries that could interfere with administration of therapy.
6. Active bacterial, viral, or fungal infection requiring systemic therapy
7. Seizure disorders requiring anticonvulsant therapy
8. Severe chronic obstructive pulmonary disease with hypoxiemia.
9. History of severe cardiac disease: New York Heart Association (NYHA) functional class III-IV, myocardial infarction within 6 months, ventricular tachyarrhythmias, dilatative cardiomyopathy, or unstable angina.
10. Uncontrolled diabetes mellitus
11. Active secondary malignancy
12. Known hypersensitivity or anaphylactic reactions to murine antibodies and proteins, to Bendamustine or mannitol.
13. Major surgery within 4 weeks of study Day 1.
14. HBsAg+
15. HCVAb+ patients with active viral replication (HCV-RNA+ with AST>2 x normal limit)
16. Any co-existing medical or psychological condition that would preclude participation in the study or compromise the patient’s ability to give informed consent, or that may affect the interpretation of the results, or render the patient at high risk from treatment complications.
17. CNS involvement
18. Chronic treatment with strong or moderate CYP3A inhibitors (e.g. ketoconazole, ritonavir, clarithromycin, itraconazole, voriconazole)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 2-years progression-free survival (PFS) of the HR patients from date of enrollment

Secondary endpoints 7

1. The proportion of molecular response (analyzed in the labs of the FIL-MRD Network)
2. The progression-free survival (PFS) of all enrolled patients, and of different subgroups (i.e TP53 mutated patients)
3. The overall survival (OS)
4. The duration of responses (DoR)
5. The proportion of complete remission (CR) before and after venetoclax in the HR group and/or in the LR not responding to R-BAC.
6. The proportion of patients that complete the expected treatment schedule
7. The safety of venetoclax when administered as consolidation or maintenance after R-BAC

Investigational products

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

Test 1

Auxiliary 3

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

Carlo Visco, MD

Public contact point

Organisation

Fondazione Italiana Linfomi Ets

Contact name

Carlo Visco, MD

Locations

1 EU/EEA country · 35 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 11 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