Bendamustine/Lenalidomide/Rituximab: Combination as a Second-Line Therapy for 1st Relapsed-Refractory MCL (R2-B)

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2012 by Fondazione Italiana Linfomi ONLUS
Sponsor:
Information provided by (Responsible Party):
Fondazione Italiana Linfomi ONLUS
ClinicalTrials.gov Identifier:
NCT01737177
First received: November 27, 2012
Last updated: November 29, 2012
Last verified: November 2012
  Purpose

This is a prospective, multicenter phase II trial designed to evaluate the safety and activity of the combination of Bendamustine, Lenalidomide and Rituximab (R2-B) in patients with first relapsed/refractory mantle cell lymphoma (MCL) and the efficacy and safety of a maintenance treatment with Lenalidomide for 18 months from the end of R2-B (from month 7 to 24) for those responding to the induction.


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

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Bendamustine, Lenalidomide and Rituximab (R2-B) Combination as a Second-Line Therapy for First Relapsed-Refractory Mantle Cell Lymphomas: A Phase II Study

Resource links provided by NLM:


Further study details as provided by Fondazione Italiana Linfomi ONLUS:

Primary Outcome Measures:
  • Complete Response (CR) rate [ Time Frame: At the end of the consolidation phase (6 months) ] [ Designated as safety issue: No ]
    Proportion of CR according to the Cheson2007 response criteria

  • Maintenance Progression Free Survival (maPFS) [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    maPFS will be defined in the maintenance cohort as the time between the date of CR/PR and the date of disease progression or death from any cause.


Secondary Outcome Measures:
  • Toxicity [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
    Incidence of grade 3 or higher Toxicity measured by CTCAE v.4 during induction and maintenance therapy

  • Overall Response Rate (ORR) [ Time Frame: at the end of the consolidation phase (6 months) ] [ Designated as safety issue: No ]
    ORR at the end of the consolidation treatment is defined as Complete Response(CR) or Partial Response according to the Cheson 2007 response criteria

  • Progression Free Survival (PFS) in all patients [ Time Frame: 42 months ] [ Designated as safety issue: No ]
    PFS will be measured from the day of enrolment and of disease progression or death from any cause

  • Overall Survival (OS) [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    OS will be defined as the date of enrolment and the date of recurrence/disease progression or death from any cause

  • Molecular response rate [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    rate of conversion to molecular remission measured by PCR

  • Molecular relapse rate during study period [ Time Frame: 42 months ] [ Designated as safety issue: No ]
    rate of conversion to molecular relapse measured by PCR

  • Disease kinetics of minimal residual disease (MRD) during study period [ Time Frame: up to 42 months ] [ Designated as safety issue: No ]
    measured by real time PCR in the bone marrow and peripheral blood

  • Cumulative incidence of second primary malignancies [ Time Frame: up to 42 months ] [ Designated as safety issue: Yes ]
    incidence of any second primary malignancies (haematological and not haematological) diagnosed after the conclusion of induction phase


Estimated Enrollment: 42
Study Start Date: April 2012
Estimated Study Completion Date: April 2017
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bendamustina, Lenalidomide, Rituximab
1 arm for all patients
Drug: Bendamustine, Lenalidomide, Rituximab

INDUCTION PHASE (COURSE 1-4)

  • Bendamustine: 70 mg/m2 on day 2 and 3 every 28
  • Lenalidomide: 10 mg/daily on day 1 to 14 of a 28 days course
  • Rituximab: 375 mg/m2 on day 1 every 28 days; only for the first cycle in the induction phase will start on day 8

CONSOLIDATION PHASE (courses 5-6)

Patients in CR and PR at the end of the induction phase

  • Lenalidomide: 15 mg/daily on day 1 to 21 of a 28 days course.
  • Rituximab: 375 mg/m2 on day 1 every 28 days

MAINTENANCE PHASE (courses 7-24)

Patients in CR or PR at the end of the consolidation treatment with Lenalidomide until disease progression or unacceptable toxicity up to 18 months (from month 7 to month 24)

- Lenalidomide: 15 mg/daily on day 1 to 21 of a 28 days


Detailed Description:

This is a phase II study, non randomized, multicenter. Patients with MCL refractory to front line therapy or in first relapse will be enrolled.

The study includes an induction phase, a consolidation phase, a maintenance phase and a follow up phase.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient has a diagnosis of MCL according to the WHO classification;
  • Patient age is ≥ 18 years;
  • Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2;
  • Understands and voluntarily signs an informed consent form;
  • Able to adhere to the study visit schedule and other protocol requirements;
  • Patients treated with one prior regimen and relapsed, or refractory to front line therapy; front line consolidation with autologous stem cell transplantation is considered to be part of first line therapy;
  • Patient has at least one site of measurable nodal disease at baseline ≥ 2.0 cm in the longest transverse diameter as determined by CT scan (MRI is allowed only if CT scan can not be performed). Note: Patients with bone marrow involvement are eligible;
  • Adequate haematological counts: ANC > 1.5 x 109/L and platelet count > 75 x 109/L unless due to bone marrow involvement by MCL;
  • Conjugated bilirubin up to 2 x ULN unless due to liver involvement by MCL;
  • Alkaline phosphatase and transaminases up to 2 x ULN unless due to liver involvement by MCL;
  • Creatinine clearance ≥ 30 ml/min; a dose reduction of Lenalidomide for patients with creatinine clearance ≥ 30 mL/min but < 50 mL/min is planned;
  • Written informed consent was obtained from the patient prior to any study-specific screening procedures;
  • Patient has the ability to swallow capsules or tablets;
  • Life expectancy ≥ 6 months;
  • Disease free of prior malignancies (a part MCL) with the exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast;

Exclusion Criteria:

  • Patients who have received an experimental drug or used an experimental medical device within 4 weeks before the planned start of treatment. Concurrent participation in non-treatment studies is allowed, if it will not interfere with participation in this study;
  • Patient has a history of CNS involvement with lymphoma;
  • Patients with previous history of malignancies (a part MCL) ≤ 3 years before study accrual with the exception of currently treated basal cell and squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix;
  • History of clinically relevant liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, rheumatologic, hematologic, psychiatric, or metabolic disturbances;
  • Patient has any other concurrent severe and/or uncontrolled medical condition(s) (e.g., uncontrolled diabetes mellitus, active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol;
  • Creatinine clearance < 30 ml/min;
  • Patient has a known history of HIV seropositivity;
  • Patient has active HBV hepatitis. The following categories of HBV positive patients but with non evidence of active hepatitis may be considered for the study and treated with R2-B (see also Section 8.1.8):
  • patient is HBsAg + with HBV DNA < 2000 UI/ml (inactive carriers); HBV DNA > 2000 UI/ml is criteria of exclusion;
  • patient is HBsAg - HBsAb +;
  • patient is HBsAg - but HBcAb +
  • Patients with HCV active hepatitis are excluded from the study. Patient with no evidence of active hepatitis and/or advanced chronic liver disease according to liver biopsy or fibro-scan evaluation may be included into the study
  • Patients have received previous treatment with either Bendamustine and/or Lenalidomide.
  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: NCT01737177

Contacts
Contact: M. Antonella Ferranti 00390131206129 segreteria@filinf.it
Contact: Daniela Gioia 00390131206066 segreteria@filinf.it

  Show 52 Study Locations
Sponsors and Collaborators
Fondazione Italiana Linfomi ONLUS
Investigators
Principal Investigator: Francesco Zaja, M.D. Clinica Ematologica - Udine - Italy
  More Information

No publications provided

Responsible Party: Fondazione Italiana Linfomi ONLUS
ClinicalTrials.gov Identifier: NCT01737177     History of Changes
Other Study ID Numbers: FIL R2-B
Study First Received: November 27, 2012
Last Updated: November 29, 2012
Health Authority: Italy: Ministry of Health

Keywords provided by Fondazione Italiana Linfomi ONLUS:
MCL
Mantle Cell Lymphoma
RELAPSED-REFRACTORY

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Bendamustine
Rituximab
Lenalidomide
Thalidomide
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Immunosuppressive Agents
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors

ClinicalTrials.gov processed this record on July 10, 2014