Rituximab, Bendamustine and Cytarabine Followed by Venetoclax in High Risk Elderly Patients With MCL

• Status: Active, not recruiting
• Trial end date: 2025-07-01
• Target enrollment: 0
• Participant gender: All

Summary

Prospective, multicenter, phase II trial designed to evaluate whether the addition of Venetoclax after rituximab, bendamustine and cytarabine (R-BAC) to high risk patients with mantle cell lymphoma improves the results of the standard R-BAC, in terms of Progression Free Survival.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Fondazione Italiana Linfomi ONLUS
• Collaborator: AbbVie
• Treatments: Bendamustine Hydrochloride; Cytarabine; Rituximab; Venetoclax

Criteria

Inclusion Criteria:

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:

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)