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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03567876
Recruitment Status : Recruiting
First Posted : June 25, 2018
Last Update Posted : July 16, 2019
Information provided by (Responsible Party):
Fondazione Italiana Linfomi ONLUS

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
Lymphoma, Mantle-Cell Drug: Venetoclax 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 .

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 130 participants
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 : September 3, 2018
Estimated Primary Completion Date : July 2020
Estimated Study Completion Date : July 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

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 Name: Venclyxto (commercial name)

Primary Outcome Measures :
  1. Progression-free survival of the High Risk patients [ Time Frame: 24 months ]
    2-years progression-free survival (PFS) of the HR patients from date of enrollment

Secondary Outcome Measures :
  1. Molecular response [ Time Frame: 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 [ Time Frame: 24 months ]
    The progression-free survival (PFS) of all enrolled patients, and of different subgroups (i.e TP53 mutated patients)

  3. Overall survival [ Time Frame: 54 months ]
    Overall survival

  4. Duration of responses [ Time Frame: 24 months ]
    Duration of responses

  5. Proportion of complete remission in High Risk and Law Risk patients [ Time Frame: 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 [ Time Frame: 30 months ]
    The proportion of patients that complete the expected treatment schedule

  7. Incidence of Treatment-Emergent Adverse Events [ Time Frame: 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

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03567876

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Contact: Claudia Peracchio 00390131033154
Contact: Antonella Ferranti 00390131033153

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A.O. SS. Antonio e Biagio e Cesare Arrigo, SC Ematologia Recruiting
Alessandria, Italy
Contact: Marco Ladetto   
Principal Investigator: Marco Ladetto, MD         
Università Politecnica delle Marche, Clinica di Ematologia Recruiting
Ancona, Italy
Contact: Guido Gini   
Principal Investigator: Guido Gini, MD         
Centro Riferimento Oncologico, S.O.C. Oncologia Medica A Not yet recruiting
Aviano, Italy
Contact: Michele Spina   
Principal Investigator: Michele Spina, MD         
IRCCS Istituto Tumori Giovanni Paolo II, UOC Ematologia Not yet recruiting
Bari, Italy
Contact: Giacomo Loseto   
Principal Investigator: Giacomo Loseto, MD         
Policlinico S. Orsola-Malpighi, Istituto di Ematologia "Seragnoli" Recruiting
Bologna, Italy
Contact: Pier Luigi Zinzani   
Principal Investigator: Pier Luigi Zinzani, Prof         
Ospedale Centrale di Bolzano, Divisione di Ematologia e T.M.O. Not yet recruiting
Bolzano, Italy
Contact: Michael Mian   
Principal Investigator: Michael Mian, Prof         
ASST Spedali Civili, Ematologia Recruiting
Brescia, Italy
Contact: Alessandro Re   
Principal Investigator: Alessandro Re, MD         
Ospedale Businco, Ematologia Recruiting
Cagliari, Italy
Contact: Maria Giuseppina Cabras   
Principal Investigator: Maria Giuseppina Cabras, MD         
Azienda Ospedaliera di Cosenza, UOC Ematologia Not yet recruiting
Cosenza, Italy
Contact: Massimo Gentile   
Principal Investigator: Massimo Gentile, MD         
Azienda Ospedaliera S. Croce e Carle, SC Ematologia Recruiting
Cuneo, Italy
Contact: Claudia Castellino   
Principal Investigator: Claudia Castellino, MD         
Azienda Ospedaliera Universitaria Careggi, Unità funzionale di Ematologia Not yet recruiting
Firenze, Italy
Contact: Benedetta Puccini   
Principal Investigator: Benedetta Puccini, MD         
Ospedale Policlinico San Martino S.S.R.L. - IRCCS per l'Oncologia, Clinica Ematologica Not yet recruiting
Genova, Italy
Contact: Marco Gobbi   
Principal Investigator: Marco Gobbi, Prof         
Ospedale Policlinico San Martino S.S.R.L. - IRCCS per l'Oncologia, Ematologia Not yet recruiting
Genova, Italy
Contact: Angela Giovanna Congiu   
Principal Investigator: Angela Giovanna Congiu, MD         
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.), Ematologia Recruiting
Meldola, Italy
Contact: Gerardo Musuraca   
Principal Investigator: Gerardo Musuraca, MD         
ASST Grande Ospedale Metropolitano Niguarda, SC Ematologia Recruiting
Milano, Italy
Contact: Vittorio Ruggero Zilioli   
Principal Investigator: Vittorio Ruggero Zilioli, MD         
Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Ematologia Not yet recruiting
Milano, Italy
Contact: Paolo Corradini   
Principal Investigator: Paolo Corradini, Prof         
Istituto Scientifico San Raffaele, Unità Linfomi - Dipartimento Oncoematologia Not yet recruiting
Milano, Italy
Contact: Andrés Ferreri   
Principal Investigator: Andrés Ferreri, MD         
Ospedale Maggiore Policlinico - Fondazione IRCCS Ca' Granda, Ematologia Recruiting
Milano, Italy
Contact: Luca Baldini   
Principal Investigator: Luca Baldini, Prof         
AOU Maggiore della Carità di Novara, SCDU Ematologia Recruiting
Novara, Italy
Contact: Luca Nassi   
Principal Investigator: Luca Nassi, MD         
Azienda Ospedaliera Universitaria di Padova, Ematologia Recruiting
Padova, Italy
Contact: Francesco Piazza   
Principal Investigator: Francesco Piazza, MD         
A.O. Ospedali Riuniti Villa Sofia-Cervello, Divisione di Ematologia Recruiting
Palermo, Italy
Contact: Caterina Patti   
Principal Investigator: Caterina Patti, MD         
IRCCS Policlinico S. Matteo, Divisione di Ematologia Not yet recruiting
Pavia, Italy
Contact: Luca Arcaini   
Principal Investigator: Luca Arcaini, Prof         
Ospedale Guglielmo Da Saliceto, UO Ematologia Not yet recruiting
Piacenza, Italy
Contact: Annalisa Arcari   
Principal Investigator: Annalisa Arcari, MD         
Ospedale delle Croci, Ematologia Recruiting
Ravenna, Italy
Contact: Monica Tani   
Principal Investigator: Monica Tani, MD         
Grande Ospedale Metropolitano Bianchi Melacrino Morelli, Ematologia Not yet recruiting
Reggio Calabria, Italy
Contact: Caterina Stelitano   
Principal Investigator: Caterina Stelitano, MD         
Azienda Unità Sanitaria Locale-IRCCS - Arcispedale Santa Maria Nuova, Ematologia Recruiting
Reggio Emilia, Italy
Contact: Francesco Merli   
Principal Investigator: Francesco Merli, MD         
Ospedale degli Infermi, UO Ematologia Not yet recruiting
Rimini, Italy
Contact: Annalia Molinari   
Principal Investigator: Annalia Molinari, MD         
Policlinico Umberto I - Università "La Sapienza", Istituto Ematologia -Dipartimento di Biotecnologie Cellulari ed Ematologia Recruiting
Roma, Italy
Contact: Maurizio Martelli   
Principal Investigator: Maurizio Martelli, Prof         
Università Cattolica S. Cuore, Ematologia Recruiting
Roma, Italy
Contact: Stefan Hohaus   
Principal Investigator: Stefan Hohaus, MD         
Istituto Clinico Humanitas, UO Ematologia Recruiting
Rozzano, Italy
Contact: Armando Santoro   
Principal Investigator: Armando Santoro, MD         
Casa Sollievo della Sofferenza, UO Ematologia Not yet recruiting
San Giovanni Rotondo, Italy
Contact: Nicola Cascavilla   
Principal Investigator: Nicola Cascavilla, MD         
Azienda Ospedaliero Universitaria Senese, UOC Ematologia Not yet recruiting
Siena, Italy
Contact: Alberto Fabbri   
Principal Investigator: Alberto Fabbri, MD         
A.O.U. Città della Salute e della Scienza di Torino, SC Ematologia Universitaria Recruiting
Torino, Italy
Contact: Federica Cavallo   
Principal Investigator: Federica Cavallo, MD         
A.O.U. Città della Salute e della Scienza di Torino, SC Ematologia Not yet recruiting
Torino, Italy
Contact: Annalisa Chiappella   
Principal Investigator: Annalisa Chiappella, MD         
Ospedale Ca' Foncello, SC Ematologia Not yet recruiting
Treviso, Italy
Contact: Piero Maria Stefani   
Principal Investigator: Piero Maria Stefani, MD         
Azienda Ospedaliera C. Panico, UOC Ematologia e Trapianto Recruiting
Tricase, Italy
Contact: Vincenzo Pavone   
Principal Investigator: Vincenzo Pavone, MD         
Azienda Sanitaria Universitaria Integrata di Udine, Clinica Ematologica Not yet recruiting
Udine, Italy
Contact: Stefano Volpetti   
Principal Investigator: Stefano Volpetti, MD         
Ospedale di Circolo, UOC Ematologia Recruiting
Varese, Italy
Contact: Michele Merli   
Principal Investigator: Michele Merli, MD         
Azienda Ospedaliera Universitaria Integrata di Verona, UO Ematologia Recruiting
Verona, Italy
Contact: Carlo Visco   
Principal Investigator: Carlo Visco, MD         
Ospedale San Bortolo, Divisione di Ematologia Recruiting
Vicenza, Italy
Contact: Maria Chiara Tisi   
Principal Investigator: Maria Chiara Tisi, MD         
Sponsors and Collaborators
Fondazione Italiana Linfomi ONLUS
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Principal Investigator: Carlo Visco, MD AOU Integrata di Verona - U.O. Ematologia -Verona -Italy

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Responsible Party: Fondazione Italiana Linfomi ONLUS Identifier: NCT03567876     History of Changes
Other Study ID Numbers: FIL_V-RBAC
First Posted: June 25, 2018    Key Record Dates
Last Update Posted: July 16, 2019
Last Verified: January 2019

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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:
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Lymphoma, Mantle-Cell
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Bendamustine Hydrochloride
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Antineoplastic Agents, Alkylating
Alkylating Agents