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

NCT01662050 | Completed Phase 2

• 1 other identifier: FIL-RBAC500
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 56

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

Conditions

Mantle Cell Lymphoma

Keywords

MCL; Mantle Cell Lymphoma; Older

Outcome Measures

Primary Outcomes (2)

• complete remission rate at the end of treatment

  The primary objective is to determine the activity \[complete remission rate (CR) according to Cheson 2007 criteria\]

  6 months

• Toxicity will be represented by the occurrence of any of the stop treatment criteria or of any episode of relevant toxicity

  Relevant toxicity: Grade 4 cytopenia lasting for more than 6 days or Grade 3-4 non-hematologic toxicity or Febrile neutropenia lasting for more than 3 consecutive days. Stop treatment criteria: 1. Occurrence of relevant toxicity for two subsequent or consecutive cycles. 2. Grade 3-4 hematological or non-hematological toxicity on day +28 of a cycle not resolving within two weeks. 3. Grade 3-4 hematological or non-hematological toxicity on day +28 of a cycle after 25% dose reduction. 4. Patient refusal to procede with further cycles due to perceived excessive toxicity. 5. Any unpredictable drug related event that suggests against study continuation

  6 months

Secondary Outcomes (6)

• the rate of molecular response

  6 months

• the progression-free survival (PFS)

  30 months

• the overall survival (OS)

  30 months

• the duration of responses (DOR)

  30 months

• the rate of completion of treatment

  6 months

Study Arms (1)

One arm for all patients.

EXPERIMENTAL

Rituximab, Bendamustine, Cytarabine

Drug: Rituximab, Bendamustine, Cytarabine.

Interventions

Rituximab, Bendamustine, Cytarabine. DRUG

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

One arm for all patients.

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Fondazione Italiana Linfomi - ETS: lead

Study Sites (56)

A.O. Policlinico Consorziale

Bari, BA, 70124, Italy

Location

IRCCS Ospedale Oncologico

Bari, BA, 70124, Italy

Location

A.O. Spedali Civili

Brescia, BS, 25100, Italy

Location

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

Trani, BT, 70031, Italy

Location

Ospedale Businco

Cagliari, CA, 09121, Italy

Location

AO Valduce

Como, CO, 22100, Italy

Location

U.O.C. Garibaldi Nesima

Catania, CT, 95125, Italy

Location

AOU Careggi

Florence, FI, 50134, Italy

Location

A.O.U. San Martino

Genova, GE, 16132, Italy

Location

PO Vito Fazzi

Lecce, LE, 73100, Italy

Location

Ospedale Cardinale G. Panico

Tricase, LE, 73039, Italy

Location

Asur - Zona Territoriale 8

Civitanova Marche, MC, 62012, Italy

Location

U.O.C. Ematologia - Policlinico Universitario

Messina, ME, 98100, Italy

Location

Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico

Milan, MI, 20122, Italy

Location

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

Milan, MI, 20153, Italy

Location

A.O. Niguarda

Milan, MI, 20162, Italy

Location

Osp. San Gerardo

Monza, MI, 20052, Italy

Location

Istituto Clinico Humanitas

Rozzano, MI, 20089, Italy

Location

Centro Oncologico Modenese (COM)

Modena, MO, 41100, Italy

Location

"La Maddalena"

Palermo, PA, 90146, Italy

Location

Ospedali Riuniti Villa Sofia - Cervello

Palermo, PA, 90146, Italy

Location

Ospedale Civile Guglielmo da Saliceto

Piacenza, PC, 29121, Italy

Location

Università di Padova

Padua, PD, 35128, Italy

Location

Presidio ospedaliero di Pescara

Pescara, PE, 65124, Italy

Location

CRO Aviano

Aviano, PN, 33081, Italy

Location

Fondazione IRCCS Policlinico San Matteo,

Pavia, PV, 27100, Italy

Location

Osp. S. Maria delle Croci

Ravenna, RA, 48121, Italy

Location

Azienda Ospedaliera "Bianchi Melacrino Morelli"

Reggio Calabria, RC, 89125, Italy

Location

Azienda Ospedaliera Arcispedale "S.Maria Nuova"

Reggio Emilia, RE, 42100, Italy

Location

A.O. San Camillo Forlanini

Roma, RM, 00152, Italy

Location

Nuovo Regina Margherita

Roma, RM, 00153, Italy

Location

Università "La Sapienza"

Roma, RM, 00161, Italy

Location

A.O. S. Giovanni Addolorata

Roma, RM, 00184, Italy

Location

Ospedale degli Infermi di Rimini

Rimini, RN, 47900, Italy

Location

Azienda ULSS 18

Rovigo, RO, 45100, Italy

Location

Osp. Umberto I

Nocera Inferiore, SA, 84014, Italy

Location

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

Salerno, SA, 84131, Italy

Location

Az. Ospedaliera Univ. Senese

Siena, SI, 53100, Italy

Location

ASL TO4

Ciriè-Ivrea-Chivasso, TO, 10043, Italy

Location

Ospedale S. Luigi Gonzaga,

Orbassano, TO, 10043, Italy

Location

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

Torino, TO, 10126, Italy

Location

AOU San Giovanni Battista-Ematologia 1

Torino, TO, 10126, Italy

Location

A.O. S. Maria di Terni

Terni, TR, 05100, Italy

Location

Azienda Ospedaliero - Universitaria di Udine

Udine, UD, 33100, Italy

Location

Ospedale di Circolo e Fondazione Macchi - Ematologia

Varese, VA, 21100, Italy

Location

Ospedale di Circolo e Fondazione Macchi - Oncologia

Varese, VA, 21100, Italy

Location

Osp. S. Andrea Vercelli

Vercelli, VC, 13100, Italy

Location

Ospedale Civile di Mirano

Mirano, VE, 30035, Italy

Location

Ospedale San Bortolo

Vicenza, VI, 36100, Italy

Location

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

Verona, VR, 37126, Italy

Location

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

Alessandria, 15121, Italy

Location

Comprensorio sanitario di Bolzano

Bolzano, 39100, Italy

Location

Ospedale Cardarelli

Campobasso, 86100, Italy

Location

A.O. Pugliese-Ciacci

Catanzaro, 88100, Italy

Location

IRST

Meldola, 47014, Italy

Location

Università del Piemonte Orientale - Novara

Novara, 28100, Italy

Location

Related Publications (2)

• 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.

  PMID: 37171620 DERIVED

• 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.

  PMID: 27927586 DERIVED

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

Rituximab; Bendamustine Hydrochloride; Cytarabine

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Carlo Visco, MD

  Ospedale ULSS 6 di Vicenza - Ematologia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 26, 2012
• First Posted: August 10, 2012
• Study Start: March 20, 2012
• Primary Completion: August 1, 2014
• Study Completion: September 11, 2017
• Last Updated: August 9, 2022

Record last verified: 2022-08

Locations

IT (56)