Phase II Study of Age-Adjusted Rituximab, Bendamustine, Cytarabine as Induction Therapy in Older Patients With MCL

NCT ID: NCT01662050

Last Updated: 2022-08-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 57 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-03-20
• Study Completion Date: 2017-09-11

Brief Summary

A phase 2 study of standard R-BAC (rituximab 375 mg/m2, bendamustine 70 mg/m2, ara-c 800 mg/m2) has been recently ultimated at the Vicenza Hematology Department involving several regional centers on both untreated and previously treated patients with Mantle Cell Lymphoma (MCL). An interim analysis conducted on 30 patients showed that rituximab + bendamustine + ara-c combination had very good clinical activity, but a quite relevant hematological toxicity, especially in previously treated and older patients (Visco C, ICML 2011 Lugano Conference, Poster 236).

Objectives:

The primary objective is to determine the activity (complete remission rate according to Cheson 2007 criteria) and safety of age-adjusted Rituximab-Bendamustine-Cytarabine (RBAC500) regimen at the end of treatment in older untreated patients with MCL.

The secondary objectives are to determine:

• The rate of molecular response (characterized by labs of the FIL)
• The progression-free survival (PFS)
• The overall survival (OS)
• The duration of responses (DOR)
• The rate of patients that complete the expected treatment schedule (6 courses)
• The rate of patients that are subject to dose reductions or delays

Detailed Description

Study End points Primary efficacy end point of the study is the proportion of CR defined according to Cheson criteria (2007) at the end of treatment (6 or 4 cycles). Primary safety end point is the occurrence of any of the stop treatment criteria or of any episode of relevant toxicity, as above defined.

Secondary end points are MRD defined response, OS, PFS and DOR (Cheson 2007). Molecular response is the proportion of patients with molecular rearrangements at baseline that become negative during treatment, measured by qualitative and quantitative PCR.

OS is measured from enrollment until death from any cause. PFS is measured from the time of enrollment until disease progression, relapse or death from any cause. DOR is measured from the first assessment that documents response (CR or PR) to the date of disease relapse or progression. Minimum follow up required for all patients will be 24 months.

Conditions

Mantle Cell Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

One arm for all patients.

Rituximab, Bendamustine, Cytarabine

Group Type: EXPERIMENTAL

Rituximab, Bendamustine, Cytarabine.

Intervention Type: DRUG

6 cycles of 28 days with Rituximab, Bendamustine and Cytarabine (R-BAC). Rituximab 375mg/mq; Bendamustine 70mg/mq; Cytarabine 500mg/mq.

Interventions

Rituximab, Bendamustine, Cytarabine.

6 cycles of 28 days with Rituximab, Bendamustine and Cytarabine (R-BAC). Rituximab 375mg/mq; Bendamustine 70mg/mq; Cytarabine 500mg/mq.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Previously untreated patients with MCL aged > 65 years if they are FIT according to the geriatric CGA assessment.
• age 60-65 years not eligible to high-dose chemotherapy plus transplantation, FIT or UNFIT according to the geriatric CGA assessment.
• ECOG performance status ≤ 2.
• Positivity for cyclin D1 and SOX11 [the latter being mandatory in cases lacking cyclin D1- or t(11;14)-negative], CD20 and CD5.
• Adequate renal function (Creatinine clearance > 40 mL/min), with preserved diuresis.
• Adequate liver function: alanine aminotransferase (ALT)/aspartate aminotransferase (AST) < 2.5 x upper limit of normal (ULN) value, total bilirubin < 2 mg/dL, unless directly attributable to the patient's tumor.
• 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.
• Written informed consent.

Exclusion Criteria

• Human immunodeficiency virus (HIV) positive.
• Previous treatment for lymphoma
• Medical conditions or organ injuries that could interfere with administration of therapy.
• Active bacterial, viral, or fungal infection requiring systemic therapy.
• Seizure disorders requiring anticonvulsant therapy.
• Severe chronic obstructive pulmonary disease with hypoxemia.
• 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.
• Uncontrolled diabetes mellitus.
• Active secondary malignancy.
• Known hypersensitivity or anaphylactic reactions to murine antibodies and proteins, to Bendamustine or mannitol.
• Major surgery within 4 weeks of study Day 1.
• HBsAg+
• HCVAb+ patients with active viral replication (HCV-RNA+ with AST > 2 x normal limit)
• 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.
• CNS involvement (a diagnostic lumbar puncture will be performed in patients with the blastoid variant of MCL)

• Minimum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fondazione Italiana Linfomi - ETS

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Carlo Visco, MD

Role: PRINCIPAL_INVESTIGATOR

Ospedale ULSS 6 di Vicenza - Ematologia

Locations

A.O. Policlinico Consorziale

Bari, BA, Italy

IRCCS Ospedale Oncologico

Bari, BA, Italy

A.O. Spedali Civili

Brescia, BS, Italy

U.O.C. Ematologia Ospedale "San Nicola Pellegrino" ASL BAT

Trani, BT, Italy

Ospedale Businco

Cagliari, CA, Italy

AO Valduce

Como, CO, Italy

U.O.C. Garibaldi Nesima

Catania, CT, Italy

AOU Careggi

Florence, FI, Italy

A.O.U. San Martino

Genova, GE, Italy

PO Vito Fazzi

Lecce, LE, Italy

Ospedale Cardinale G. Panico

Tricase, LE, Italy

Asur - Zona Territoriale 8

Civitanova Marche, MC, Italy

U.O.C. Ematologia - Policlinico Universitario

Messina, ME, Italy

Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico

Milan, MI, Italy

A.O. S. Carlo Borromeo di Milano Unità Semplice di Trapianto Midollo - A.O.S.Carlo Borromeo

Milan, MI, Italy

A.O. Niguarda

Milan, MI, Italy

Osp. San Gerardo

Monza, MI, Italy

Istituto Clinico Humanitas

Rozzano, MI, Italy

Centro Oncologico Modenese (COM)

Modena, MO, Italy

"La Maddalena"

Palermo, PA, Italy

Ospedali Riuniti Villa Sofia - Cervello

Palermo, PA, Italy

Ospedale Civile Guglielmo da Saliceto

Piacenza, PC, Italy

Università di Padova

Padua, PD, Italy

Presidio ospedaliero di Pescara

Pescara, PE, Italy

CRO Aviano

Aviano, PN, Italy

Fondazione IRCCS Policlinico San Matteo,

Pavia, PV, Italy

Osp. S. Maria delle Croci

Ravenna, RA, Italy

Azienda Ospedaliera "Bianchi Melacrino Morelli"

Reggio Calabria, RC, Italy

Azienda Ospedaliera Arcispedale "S.Maria Nuova"

Reggio Emilia, RE, Italy

A.O. San Camillo Forlanini

Roma, RM, Italy

Nuovo Regina Margherita

Roma, RM, Italy

Università "La Sapienza"

Roma, RM, Italy

A.O. S. Giovanni Addolorata

Roma, RM, Italy

Ospedale degli Infermi di Rimini

Rimini, RN, Italy

Azienda ULSS 18

Rovigo, RO, Italy

Osp. Umberto I

Nocera Inferiore, SA, Italy

A.O.U. San Giovanni di Dio e Ruggi d'Aragona

Salerno, SA, Italy

Az. Ospedaliera Univ. Senese

Siena, SI, Italy

ASL TO4

Ciriè-Ivrea-Chivasso, TO, Italy

Ospedale S. Luigi Gonzaga,

Orbassano, TO, Italy

A.O.U. S. Giovanni Battista -Ematologia 2

Torino, TO, Italy

AOU San Giovanni Battista-Ematologia 1

Torino, TO, Italy

A.O. S. Maria di Terni

Terni, TR, Italy

Azienda Ospedaliero - Universitaria di Udine

Udine, UD, Italy

Ospedale di Circolo e Fondazione Macchi - Ematologia

Varese, VA, Italy

Ospedale di Circolo e Fondazione Macchi - Oncologia

Varese, VA, Italy

Osp. S. Andrea Vercelli

Vercelli, VC, Italy

Ospedale Civile di Mirano

Mirano, VE, Italy

Ospedale San Bortolo

Vicenza, VI, Italy

Ospedale Policlinico G.B. Rossi (Borgo Roma) Di Verona

Verona, VR, Italy

A.O. SS. Antonio e Biagio e C. Arrigo

Alessandria, , Italy

Comprensorio sanitario di Bolzano

Bolzano, , Italy

Ospedale Cardarelli

Campobasso, , Italy

A.O. Pugliese-Ciacci

Catanzaro, , Italy

IRST

Meldola, , Italy

Università del Piemonte Orientale - Novara

Novara, , Italy

Countries

Italy

References

Tisi MC, Moia R, Patti C, Evangelista A, Ferrero S, Spina M, Tani M, Botto B, Celli M, Puccini B, Cencini E, Di Rocco A, Chini C, Ghiggi C, Zambello R, Zanni M, Sciarra R, Bruna R, Ferrante M, Pileri SA, Quaglia FM, Stelitano C, Re A, Volpetti S, Zilioli VR, Arcari A, Merli F, Visco C. Long-term follow-up of rituximab plus bendamustine and cytarabine in older patients with newly diagnosed MCL. Blood Adv. 2023 Aug 8;7(15):3916-3924. doi: 10.1182/bloodadvances.2023009744.

Reference Type: DERIVED

PMID: 37171620 (View on PubMed)

Visco C, Chiappella A, Nassi L, Patti C, Ferrero S, Barbero D, Evangelista A, Spina M, Molinari A, Rigacci L, Tani M, Rocco AD, Pinotti G, Fabbri A, Zambello R, Finotto S, Gotti M, Carella AM, Salvi F, Pileri SA, Ladetto M, Ciccone G, Gaidano G, Ruggeri M, Martelli M, Vitolo U. Rituximab, bendamustine, and low-dose cytarabine as induction therapy in elderly patients with mantle cell lymphoma: a multicentre, phase 2 trial from Fondazione Italiana Linfomi. Lancet Haematol. 2017 Jan;4(1):e15-e23. doi: 10.1016/S2352-3026(16)30185-5. Epub 2016 Dec 5.

Reference Type: DERIVED

PMID: 27927586 (View on PubMed)

Other Identifiers

FIL-RBAC500

Identifier Type: -

Identifier Source: org_study_id