Venetoclax after chemotherapy R-BAC in high-risk elderly patients with mantle cell lymphoma
- Conditions
- Mantle Cell Lymphoma in elderly patientsMedDRA version: 20.0 Level: LLT Classification code 10026799 Term: Mantle cell lymphoma NOS System Organ Class: 100000004864Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2017-004628-31-IT
- Lead Sponsor
- Fondazione Italiana Linfomi ONLUS
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- Target Recruitment
- 130
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, FIT or UNFIT according to the geriatric CGA assessment.
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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 100
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)
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: 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.;Secondary Objective: Not applicable;Primary end point(s): 2-years progression-free survival (PFS) of the HR patients from date of enrollment;Timepoint(s) of evaluation of this end point: 24 months
- Secondary Outcome Measures
Name Time Method <br> Timepoint(s) of evaluation of this end point: •10 and 30 months<br> •24 months<br> •54 months<br> •24 months<br> •6 and 10 months<br> •30 months<br> •10 and 30 months<br> ;<br> Secondary end point(s): •The proportion of molecular response (analyzed in the labs of the FIL-MRD Network)<br> •The progression-free survival (PFS) of all enrolled patients, and of different subgroups (i.e TP53 mutated patients)<br> •The overall survival (OS)<br> •The duration of responses (DoR)<br> •The proportion of complete remission (CR) before and after venetoclax in the HR group and/or in the LR not responding to R-BAC.<br> •The proportion of patients that complete the expected treatment schedule<br> •The safety of venetoclax when administered as consolidation or maintenance after R-BAC<br>