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

Sponsor
Fondazione Italiana Linfomi ONLUS (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT03567876
Collaborator
AbbVie (Industry)
141
Enrollment
35
Locations
1
Arm
81.9
Anticipated Duration (Months)
4
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

The aim of the study is to improve long term results of R-BAC, consolidating patients with high-risk (HR) features (defined as: elevated Ki67 and/or blastoid cytology and/or TP53 mutation after central pathology review) with Venetoclax (ABT-199), which has demonstrated relevant single agent activity in relapsed/refractory MCL in a Phase 1-2 trial.

The updated Progression Free Survival curves of the R-BAC500 trial has shown that the expected 2-years PFS for patients with HR disease is 40% (H0), as compared to low-risk patients (LR) that have a 2-years PFS of 100%. The addition of Venetoclax to HR patients after R-BAC is expected to improve results and efficacy of this regimen in this "difficult -to- treat" population, that represents approximately 40-45 % of newly diagnosed elderly patients with MCL. It appears reasonable to treat with the experimental drug also LR patients that do not respond appropriately (less than CR) at the end of R-BAC. Since the number of such LR patients is hardly predictable based on the present experience with R-BAC500 trial, the analysis of this sub-cohort will be of exploratory nature, and thus assessed separately.

The study objective is to evaluate whether the addition of venetoclax after R-BAC to HR patients improves the results of the standard R-BAC, in terms of Progression Free Survival .

Study Design

Study Type:
Interventional
Actual Enrollment :
141 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Rituximab, Bendamustine and Cytarabine Followed by Venetoclax (V-RBAC) in High-risk Elderly Patients With Mantle Cell Lymphoma (MCL)
Actual Study Start Date :
Sep 3, 2018
Actual Primary Completion Date :
Jul 26, 2021
Anticipated Study Completion Date :
Jul 1, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: V-RBAC (RBAC followed by Venetoclax)

Induction phase: RBAC --> up to 6 cycles for low risk (LR) patients and up to 4 cycles for high risk (HR) patients. Patients proceeding to Venetoclax treatment will receive consolidation with single agent Venetoclax 800 mg/die x 4 28d cycles (with initial ramp-up dose) of each consolidation cycle. Consolidation will be followed by maintenance with single agent Venetoclax 400 mg/die (V maint ) for a total of 2 years (4 months consolidation+20 months maintenance).

Drug: Venetoclax
Consolidation and maintenance phases with Venetoclax (for a total of 2 years) after an induction phase R-BAC (up to 6 cycles for law risk patients and up to 4 cycles for high risk patients)
Other Names:
  • Venclyxto (commercial name)

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Progression-free survival of the High Risk patients [24 months]

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

    Secondary Outcome Measures

    1. Molecular response [10 months and 30 months]

      The proportion of molecular response (analyzed in the labs of the FIL- MRD Network)

    2. Progression-free survival of all patients and different subgroups [24 months]

      The progression-free survival (PFS) of all enrolled patients, and of different subgroups (i.e TP53 mutated patients)

    3. Overall survival [54 months]

      Overall survival

    4. Duration of responses [24 months]

      Duration of responses

    5. Proportion of complete remission in High Risk and Law Risk patients [6 months and 10 months]

      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. Completed expected treatment schedule [30 months]

      The proportion of patients that complete the expected treatment schedule

    7. Incidence of Treatment-Emergent Adverse Events [10 months and 30 months]

      The proportion of patients with adverse events as assessed by CTCAE 4.03 during venetoclax administration as consolidation or maintenance after R-BAC

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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)

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 A.O. SS. Antonio e Biagio e Cesare Arrigo, SC Ematologia Alessandria Italy
    2 Università Politecnica delle Marche, Clinica di Ematologia Ancona Italy
    3 Centro Riferimento Oncologico, S.O.C. Oncologia Medica A Aviano Italy
    4 IRCCS Istituto Tumori Giovanni Paolo II, UOC Ematologia Bari Italy
    5 Policlinico S. Orsola-Malpighi, Istituto di Ematologia "Seragnoli" Bologna Italy
    6 ASST Spedali Civili, Ematologia Brescia Italy
    7 Ospedale Businco, Ematologia Cagliari Italy
    8 Azienda Ospedaliera S. Croce e Carle, SC Ematologia Cuneo Italy
    9 Azienda Ospedaliera Universitaria Careggi, Unità funzionale di Ematologia Firenze Italy
    10 Ospedale Policlinico San Martino S.S.R.L. - IRCCS per l'Oncologia, Clinica Ematologica Genova Italy
    11 Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.), Ematologia Meldola Italy
    12 ASST Grande Ospedale Metropolitano Niguarda, SC Ematologia Milano Italy
    13 Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Ematologia Milano Italy
    14 Istituto Scientifico San Raffaele, Unità Linfomi - Dipartimento Oncoematologia Milano Italy
    15 Ospedale Maggiore Policlinico - Fondazione IRCCS Ca' Granda, Ematologia Milano Italy
    16 AOU Maggiore della Carità di Novara, SCDU Ematologia Novara Italy
    17 Azienda Ospedaliera Universitaria di Padova, Ematologia Padova Italy
    18 A.O. Ospedali Riuniti Villa Sofia-Cervello, Divisione di Ematologia Palermo Italy
    19 IRCCS Policlinico S. Matteo, Divisione di Ematologia Pavia Italy
    20 Ospedale Guglielmo Da Saliceto, UO Ematologia Piacenza Italy
    21 Ospedale delle Croci, Ematologia Ravenna Italy
    22 Grande Ospedale Metropolitano Bianchi Melacrino Morelli, Ematologia Reggio Calabria Italy
    23 Azienda Unità Sanitaria Locale-IRCCS - Arcispedale Santa Maria Nuova, Ematologia Reggio Emilia Italy
    24 Ospedale degli Infermi, UO Ematologia Rimini Italy
    25 Policlinico Umberto I - Università "La Sapienza", Istituto Ematologia -Dipartimento di Biotecnologie Cellulari ed Ematologia Roma Italy
    26 Università Cattolica S. Cuore, Ematologia Roma Italy
    27 Istituto Clinico Humanitas, UO Ematologia Rozzano Italy
    28 A.O.U. Città della Salute e della Scienza di Torino, SC Ematologia Universitaria Torino Italy
    29 A.O.U. Città della Salute e della Scienza di Torino, SC Ematologia Torino Italy
    30 Ospedale Ca' Foncello, SC Ematologia Treviso Italy
    31 Azienda Ospedaliera C. Panico, UOC Ematologia e Trapianto Tricase Italy
    32 Azienda Sanitaria Universitaria Integrata di Udine, Clinica Ematologica Udine Italy
    33 Ospedale di Circolo, UOC Ematologia Varese Italy
    34 Azienda Ospedaliera Universitaria Integrata di Verona, UO Ematologia Verona Italy
    35 Ospedale San Bortolo, Divisione di Ematologia Vicenza Italy

    Sponsors and Collaborators

    • Fondazione Italiana Linfomi ONLUS
    • AbbVie

    Investigators

    • Principal Investigator: Carlo Visco, MD, AOU Integrata di Verona - U.O. Ematologia -Verona -Italy

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Fondazione Italiana Linfomi ONLUS
    ClinicalTrials.gov Identifier:
    NCT03567876
    Other Study ID Numbers:
    • FIL_V-RBAC
    First Posted:
    Jun 26, 2018
    Last Update Posted:
    Aug 2, 2022
    Last Verified:
    Aug 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Fondazione Italiana Linfomi ONLUS
    Mantle cell lymphoma
    Elderly patients
    First line
    Additional relevant MeSH terms:
    Lymphoma
    Lymphoma, Mantle-Cell
    Venetoclax

    Study Results

    No Results Posted as of Aug 2, 2022