Phase II Study of Age-Adjusted Rituximab, Bendamustine, Cytarabine as Induction Therapy in Older Patients With MCL
- Conditions
- Mantle Cell Lymphoma
- Interventions
- Drug: Rituximab, Bendamustine, Cytarabine.
- Registration Number
- NCT01662050
- Lead Sponsor
- Fondazione Italiana Linfomi - ETS
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 57
- 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.
- 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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description One arm for all patients. Rituximab, Bendamustine, Cytarabine. Rituximab, Bendamustine, Cytarabine
- Primary Outcome Measures
Name Time Method complete remission rate at the end of treatment 6 months The primary objective is to determine the activity \[complete remission rate (CR) according to Cheson 2007 criteria\]
Toxicity will be represented by the occurrence of any of the stop treatment criteria or of any episode of relevant toxicity 6 months 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
- Secondary Outcome Measures
Name Time Method the rate of molecular response 6 months the rate of molecular response (characterized by labs of the FIL)
the progression-free survival (PFS) 30 months 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.
the overall survival (OS) 30 months the overall survival (OS) is defined as the time from enrollment to death from any cause
the duration of responses (DOR) 30 months the duration of responses (DOR)
the rate of completion of treatment 6 months the rate of patients that complete the expected treatment schedule (6 courses)
the rate of dose reductions or delays 6 months the rate of patients that are subject to dose reductions or delays
Trial Locations
- Locations (56)
AOU Careggi
🇮🇹Firenze, FI, Italy
IRCCS Ospedale Oncologico
🇮🇹Bari, BA, Italy
Ospedale degli Infermi di Rimini
🇮🇹Rimini, RN, Italy
U.O.C. Garibaldi Nesima
🇮🇹Catania, CT, Italy
A.O. Niguarda
🇮🇹Milano, MI, Italy
Osp. Umberto I
🇮🇹Nocera Inferiore, SA, Italy
Ospedale Policlinico G.B. Rossi (Borgo Roma) Di Verona
🇮🇹Verona, VR, Italy
ASL TO4
🇮🇹Ciriè-Ivrea-Chivasso, TO, Italy
Ospedale di Circolo e Fondazione Macchi - Ematologia
🇮🇹Varese, VA, Italy
A.O.U. S. Giovanni Battista -Ematologia 2
🇮🇹Torino, TO, Italy
U.O.C. Ematologia Ospedale "San Nicola Pellegrino" ASL BAT
🇮🇹Trani, BT, Italy
A.O. Spedali Civili
🇮🇹Brescia, BS, Italy
Ospedale Civile Guglielmo da Saliceto
🇮🇹Piacenza, PC, Italy
A.O. Policlinico Consorziale
🇮🇹Bari, BA, Italy
Ospedale Businco
🇮🇹Cagliari, CA, Italy
Osp. San Gerardo
🇮🇹Monza, MI, Italy
AO Valduce
🇮🇹Como, CO, Italy
A.O.U. San Martino
🇮🇹Genova, GE, Italy
U.O.C. Ematologia - Policlinico Universitario
🇮🇹Messina, ME, Italy
Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
🇮🇹Milano, MI, Italy
Istituto Clinico Humanitas
🇮🇹Rozzano, MI, Italy
"La Maddalena"
🇮🇹Palermo, PA, Italy
Università di Padova
🇮🇹Padova, PD, Italy
CRO Aviano
🇮🇹Aviano, PN, Italy
Osp. S. Maria delle Croci
🇮🇹Ravenna, RA, Italy
Azienda ULSS 18
🇮🇹Rovigo, RO, Italy
Nuovo Regina Margherita
🇮🇹Roma, RM, Italy
Presidio ospedaliero di Pescara
🇮🇹Pescara, PE, Italy
Azienda Ospedaliera "Bianchi Melacrino Morelli"
🇮🇹Reggio Calabria, RC, Italy
Azienda Ospedaliera Arcispedale "S.Maria Nuova"
🇮🇹Reggio Emilia, RE, Italy
A.O.U. San Giovanni di Dio e Ruggi d'Aragona
🇮🇹Salerno, SA, Italy
Fondazione IRCCS Policlinico San Matteo,
🇮🇹Pavia, PV, Italy
Az. Ospedaliera Univ. Senese
🇮🇹Siena, SI, Italy
Ospedale San Bortolo
🇮🇹Vicenza, VI, Italy
Università "La Sapienza"
🇮🇹Roma, RM, Italy
A.O. S. Giovanni Addolorata
🇮🇹Roma, RM, Italy
Ospedale S. Luigi Gonzaga,
🇮🇹Orbassano, TO, Italy
AOU San Giovanni Battista-Ematologia 1
🇮🇹Torino, TO, Italy
Ospedale Civile di Mirano
🇮🇹Mirano, VE, Italy
Ospedale di Circolo e Fondazione Macchi - Oncologia
🇮🇹Varese, VA, Italy
Osp. S. Andrea Vercelli
🇮🇹Vercelli, VC, Italy
A.O. SS. Antonio e Biagio e C. Arrigo
🇮🇹Alessandria, Italy
Università del Piemonte Orientale - Novara
🇮🇹Novara, Italy
Comprensorio sanitario di Bolzano
🇮🇹Bolzano, Italy
Ospedale Cardarelli
🇮🇹Campobasso, Italy
A.O. Pugliese-Ciacci
🇮🇹Catanzaro, Italy
IRST
🇮🇹Meldola, Italy
PO Vito Fazzi
🇮🇹Lecce, LE, Italy
Ospedale Cardinale G. Panico
🇮🇹Tricase, LE, Italy
Asur - Zona Territoriale 8
🇮🇹Civitanova Marche, MC, Italy
A.O. S. Carlo Borromeo di Milano Unità Semplice di Trapianto Midollo - A.O.S.Carlo Borromeo
🇮🇹Milano, MI, Italy
A.O. San Camillo Forlanini
🇮🇹Roma, RM, Italy
Centro Oncologico Modenese (COM)
🇮🇹Modena, MO, Italy
Ospedali Riuniti Villa Sofia - Cervello
🇮🇹Palermo, PA, Italy
Azienda Ospedaliero - Universitaria di Udine
🇮🇹Udine, UD, Italy
A.O. S. Maria di Terni
🇮🇹Terni, TR, Italy