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

Mantle Cell Lymphoma Clinical Trial

— FIL-RBAC500  

Official title:

Phase II Study of Age-Adjusted R-BAC (Rituximab, Bendamustine, Cytarabine) as Induction Therapy in Older Patients With Mantle Cell Lymphoma (MCL)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01662050
• Other study ID #: FIL-RBAC500
• Status: Completed
• Phase: Phase 2
• Start date: March 20, 2012
• Est. completion date: September 11, 2017

Study information

• Verified date: August 2022
• Source: Fondazione Italiana Linfomi ONLUS
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 57
• Est. completion date: September 11, 2017
• Est. primary completion date: August 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Mantle-Cell
• Mantle Cell Lymphoma

Intervention

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

Locations

Country	Name	City	State
Italy	A.O. SS. Antonio e Biagio e C. Arrigo	Alessandria
Italy	CRO Aviano	Aviano	PN
Italy	A.O. Policlinico Consorziale	Bari	BA
Italy	IRCCS Ospedale Oncologico	Bari	BA
Italy	Comprensorio sanitario di Bolzano	Bolzano
Italy	A.O. Spedali Civili	Brescia	BS
Italy	Ospedale Businco	Cagliari	CA
Italy	Ospedale Cardarelli	Campobasso
Italy	U.O.C. Garibaldi Nesima	Catania	CT
Italy	A.O. Pugliese-Ciacci	Catanzaro
Italy	ASL TO4	Ciriè-Ivrea-Chivasso	TO
Italy	Asur - Zona Territoriale 8	Civitanova Marche	MC
Italy	AO Valduce	Como	CO
Italy	AOU Careggi	Firenze	FI
Italy	A.O.U. San Martino	Genova	GE
Italy	PO Vito Fazzi	Lecce	LE
Italy	IRST	Meldola
Italy	U.O.C. Ematologia - Policlinico Universitario	Messina	ME
Italy	A.O. Niguarda	Milano	MI
Italy	A.O. S. Carlo Borromeo di Milano Unità Semplice di Trapianto Midollo - A.O.S.Carlo Borromeo	Milano	MI
Italy	Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico	Milano	MI
Italy	Ospedale Civile di Mirano	Mirano	VE
Italy	Centro Oncologico Modenese (COM)	Modena	MO
Italy	Osp. San Gerardo	Monza	MI
Italy	Osp. Umberto I	Nocera Inferiore	SA
Italy	Università del Piemonte Orientale - Novara	Novara
Italy	Ospedale S. Luigi Gonzaga,	Orbassano	TO
Italy	Università di Padova	Padova	PD
Italy	"La Maddalena"	Palermo	PA
Italy	Ospedali Riuniti Villa Sofia - Cervello	Palermo	PA
Italy	Fondazione IRCCS Policlinico San Matteo,	Pavia	PV
Italy	Presidio ospedaliero di Pescara	Pescara	PE
Italy	Ospedale Civile Guglielmo da Saliceto	Piacenza	PC
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	Ospedale degli Infermi di Rimini	Rimini	RN
Italy	A.O. S. Giovanni Addolorata	Roma	RM
Italy	A.O. San Camillo Forlanini	Roma	RM
Italy	Nuovo Regina Margherita	Roma	RM
Italy	Università "La Sapienza"	Roma	RM
Italy	Azienda ULSS 18	Rovigo	RO
Italy	Istituto Clinico Humanitas	Rozzano	MI
Italy	A.O.U. San Giovanni di Dio e Ruggi d'Aragona	Salerno	SA
Italy	Az. Ospedaliera Univ. Senese	Siena	SI
Italy	A.O. S. Maria di Terni	Terni	TR
Italy	A.O.U. S. Giovanni Battista -Ematologia 2	Torino	TO
Italy	AOU San Giovanni Battista-Ematologia 1	Torino	TO
Italy	U.O.C. Ematologia Ospedale "San Nicola Pellegrino" ASL BAT	Trani	BT
Italy	Ospedale Cardinale G. Panico	Tricase	LE
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 Policlinico G.B. Rossi (Borgo Roma) Di Verona	Verona	VR
Italy	Ospedale San Bortolo	Vicenza	VI

Sponsors (1)

Lead Sponsor	Collaborator
Fondazione Italiana Linfomi ONLUS

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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: Occurrence of relevant toxicity for two subsequent or consecutive cycles.; Grade 3-4 hematological or non-hematological toxicity on day +28 of a cycle not resolving within two weeks.; Grade 3-4 hematological or non-hematological toxicity on day +28 of a cycle after 25% dose reduction.; Patient refusal to procede with further cycles due to perceived excessive toxicity.; Any unpredictable drug related event that suggests against study continuation	6 months
Secondary	the rate of molecular response	the rate of molecular response (characterized by labs of the FIL)	6 months
Secondary	the progression-free survival (PFS)	the progression-free survival (PFS)is defined as the time from enrollment to complete remission with disappearance of all evidence of disease, disease progression or relapse or death from any cause.	30 months
Secondary	the overall survival (OS)	the overall survival (OS) is defined as the time from enrollment to death from any cause	30 months
Secondary	the duration of responses (DOR)	the duration of responses (DOR)	30 months
Secondary	the rate of completion of treatment	the rate of patients that complete the expected treatment schedule (6 courses)	6 months
Secondary	the rate of dose reductions or delays	the rate of patients that are subject to dose reductions or delays	6 months