Phase II Study of Age‐Adjusted Rituximab, Bendamustine, Cytarabine as Induction Therapy in Older Patients With Mantle Cell Lymphoma (FIL-RBAC500)

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by Fondazione Italiana Linfomi ONLUS
Sponsor:
Information provided by (Responsible Party):
Fondazione Italiana Linfomi ONLUS
ClinicalTrials.gov Identifier:
NCT01662050
First received: June 26, 2012
Last updated: February 20, 2014
Last verified: November 2013
  Purpose

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

Condition Intervention Phase
Mantle Cell Lymphoma
Drug: Rituximab, Bendamustine, Cytarabine.
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: Phase II Study of Age‐Adjusted R‐BAC (Rituximab, Bendamustine, Cytarabine) as Induction Therapy in Older Patients With Mantle Cell Lymphoma (MCL)

Resource links provided by NLM:


Further study details as provided by Fondazione Italiana Linfomi ONLUS:

Primary Outcome Measures:
  • complete remission rate at the end of treatment [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

    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:
  • the rate of molecular response [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    the rate of molecular response (characterized by labs of the FIL)

  • the progression-free survival (PFS) [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    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) [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    the overall survival (OS) is defined as the time from enrollment to death from any cause

  • the duration of responses (DOR) [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    the duration of responses (DOR)

  • the rate of completion of treatment [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    the rate of patients that complete the expected treatment schedule (6 courses)

  • the rate of dose reductions or delays [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    the rate of patients that are subject to dose reductions or delays


Estimated Enrollment: 57
Study Start Date: February 2012
Estimated Study Completion Date: January 2016
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
One arm for all patients.
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.

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.

  Eligibility

Ages Eligible for Study:   65 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01662050

  Show 57 Study Locations
Sponsors and Collaborators
Fondazione Italiana Linfomi ONLUS
  More Information

No publications provided

Responsible Party: Fondazione Italiana Linfomi ONLUS
ClinicalTrials.gov Identifier: NCT01662050     History of Changes
Other Study ID Numbers: FIL-RBAC500
Study First Received: June 26, 2012
Last Updated: February 20, 2014
Health Authority: Italy: Ministry of Health

Keywords provided by Fondazione Italiana Linfomi ONLUS:
MCL
Mantle Cell Lymphoma
Older

Additional relevant MeSH terms:
Lymphoma, Mantle-Cell
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Rituximab
Bendamustine
Cytarabine
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Antineoplastic Agents, Alkylating
Alkylating Agents

ClinicalTrials.gov processed this record on September 29, 2014