Clinical Trials /

Bendamustine and Rituximab Induction Therapy and Maintenance Rituximab and Lenalidomide in Previously Untreated CLL/SLL

NCT01754857

Description:

The investigators propose a treatment strategy where patients are treated with induction chemoimmunotherapy consisting of rituximab + bendamustine for 6 cycles, followed by initiation of maintenance rituximab and lenalidomide among patients achieving an objective response (i.e., at least stable disease with some tumor shrinkage) to induction therapy. The goal of maintenance therapy will be to capitalize on the cytoreduction following induction chemotherapy with a maintenance regimen that has also shown promising activity in CLL, in order to allow for improved PFS in this population.

Related Conditions:
  • Chronic Lymphocytic Leukemia
  • Small Lymphocytic Leukemia
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase II Study of Bendamustine and Rituximab Induction Chemoimmunotherapy Followed by Maintenance Rituximab (Rituxan®) and Lenalidomide (Revlimid®) in Previously Untreated Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL)
  • Official Title: HO11414: Phase II Study of Bendamustine and Rituximab Induction Chemoimmunotherapy Followed by Maintenance Rituximab (Rituxan®) and Lenalidomide (Revlimid®) in Previously Untreated Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL)

Clinical Trial IDs

  • ORG STUDY ID: HO11414
  • NCT ID: NCT01754857

Conditions

  • Lymphoid Leukemia
  • Small Lymphocytic Lymphoma
  • Lymphoma, Non-Hodgkin

Interventions

DrugSynonymsArms
Bendamustine HydrochlorideTreatment (bendamustine, rituximab, lenalidomide)
RituximabTreatment (bendamustine, rituximab, lenalidomide)
LenalidomidTreatment (bendamustine, rituximab, lenalidomide)

Purpose

The investigators propose a treatment strategy where patients are treated with induction chemoimmunotherapy consisting of rituximab + bendamustine for 6 cycles, followed by initiation of maintenance rituximab and lenalidomide among patients achieving an objective response (i.e., at least stable disease with some tumor shrinkage) to induction therapy. The goal of maintenance therapy will be to capitalize on the cytoreduction following induction chemotherapy with a maintenance regimen that has also shown promising activity in CLL, in order to allow for improved PFS in this population.

Trial Arms

NameTypeDescriptionInterventions
Treatment (bendamustine, rituximab, lenalidomide)ExperimentalINDUCTION CHEMOIMMUNOTHERAPY: Patients receive bendamustine hydrochloride IV over 30-60 minutes on days 1 and 2 and rituximab IV on day 1 (up to day 5 of course 1 only). Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients achieving CR, PR, or stable disease proceed to maintenance therapy. Patients with objective response after 4 courses are eligible to proceed to maintenance therapy if ongoing induction therapy is likely associated with unacceptable toxicity. MAINTENANCE THERAPY: Beginning 6-12 weeks after completion of induction chemoimmunotherapy, patients receive rituximab IV on day 1 of every odd-numbered course and lenalidomide PO daily on days 1-28. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity. Patients experiencing excessive toxicity from lenalidomide may continue maintenance therapy with rituximab alone.
  • Bendamustine Hydrochloride
  • Rituximab
  • Lenalidomid

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically confirmed chronic lymphocytic leukemia (CLL)/small lymphocytic
             lymphoma (SLL)

          -  No prior cytotoxic chemotherapy for their disease; prior therapy with single-agent
             rituximab is permitted

          -  Understand and voluntarily sign an informed consent document

          -  In cases of SLL, subjects must have at least one bidimensionally measurable lesion at
             least >= 1.5 cm measured in one dimension

          -  Eastern Cooperative Oncology Group (ECOG) performance status of =< 2 at study entry

          -  Absolute neutrophil count >= 1500/uL

          -  Platelet count >= 100,000/uL

          -  Subjects with neutrophils < 1500/uL or platelets < 100,000/uL with splenomegaly or
             extensive bone marrow involvement as the etiology for their cytopenias are eligible

          -  Subjects must have adequate renal function with a creatinine clearance of >= 40
             mL/min as determined by the Cockcroft-Gault calculation

          -  Total bilirubin =< 2 x upper limit laboratory normal (ULN); subjects with
             non-clinically significant elevations of bilirubin due to Gilbert's disease are not
             required to meet these criteria

          -  Serum transaminases aspartate aminotransferase (AST) (serum glutamic oxaloacetic
             transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate
             transaminase [SGPT]) =< 5 x ULN

          -  Serum alkaline phosphatase =< 5 x ULN

          -  Disease-free of prior malignancies for >= 2 years with the exception of basal or
             squamous cell skin carcinoma, carcinoma "in situ" of the breast or cervix, or
             localized prostate cancer (treated definitively with hormone therapy, radiotherapy,
             or surgery)

          -  Life expectancy of at least 3 months

          -  All study participants must be willing to be registered into the mandatory Revlimid
             REMS program after completion of induction chemoimmunotherapy and prior to
             maintenance therapy, and be willing and able to comply with the requirements of the
             Revlimid REMS program

          -  Subjects must not have a known history of hypersensitivity to mannitol

          -  Prior therapy with rituximab is permitted, even in the setting of
             rituximab-refractory disease

          -  Females of reproductive potential must adhere to the scheduled pregnancy testing as
             required in the Revlimid REMS program

          -  Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (subjects
             intolerant to aspirin may use warfarin or low molecular weight heparin) if clinically
             indicated

          -  Females of childbearing potential (FCBP) must have a negative serum or urine
             pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days and again
             within 24 hours prior to prescribing lenalidomide for cycle 1 (prescriptions must be
             filled within 7 days as required by the Revlimid REMS® program) and must either
             commit to continued abstinence from heterosexual intercourse or begin TWO acceptable
             methods of birth control, one highly effective method and one additional effective
             method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide; FCBP
             must also agree to ongoing pregnancy testing; men must agree to use a latex condom
             during sexual contact with a FCBP even if they have had a successful vasectomy

        Exclusion Criteria:

          -  Any serious medical condition, laboratory abnormality, or psychiatric illness that
             would prevent the subject from signing the informed consent document or complying
             with the protocol treatment

          -  Pregnant or breast-feeding females; lactating females must agree not to breast-feed
             while taking lenalidomide

          -  Any condition, including the presence of laboratory abnormalities, which places the
             subject at unacceptable risk if he/she were to participate in the study or confounds
             the ability to interpret data from the study

          -  Subjects are not eligible if there is a prior history or current evidence of central
             nervous system or leptomeningeal involvement

          -  Known hypersensitivity to thalidomide

          -  Concurrent use of other anti-cancer agents or treatments

          -  Known to be positive for human immunodeficiency virus (HIV) or infectious hepatitis
             (type B or C)

          -  Prior malignancy, except for adequately treated basal cell or squamous cell skin
             cancer, in situ cervical or breast cancer, or other cancer from which the subject has
             been disease free for at least 2 years

          -  Severe or life-threatening anaphylaxis or hypersensitivity reaction when previously
             exposed to rituximab or other monoclonal antibody therapy

          -  Chronic hepatitis B or hepatitis C infection

          -  New York Heart Association class 3-4 heart failure

          -  More than one grade 2 or higher transaminase elevation
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Time to progression
Time Frame:Up to 30 months
Safety Issue:
Description:The primary objective is progression-free survival (PFS). Tumor measurements and disease assessments will be performed at the time of screening, following cycles 3 and 6 of induction chemotherapy, every 4 cycles during the maintenance portion of treatment, and at the end of treatment (EOT). Subjects with clinical evidence of progression prior to a planned disease assessment will be evaluated at the time of clinically suspected progression. Follow-up visits for disease assessment will occur every 3 months after the EOT visit until PD, initiation of alternate anti-neoplastic therapy, decision by the subject to withdraw from the study, or death. The follow-up period will begin after the EOT visit, and all subjects will be followed for at least 2 years after completion of therapy or until death or progression and until the last patient has been followed for at least 1 year following completion of therapy.

Secondary Outcome Measures

Measure:Objective Response Rates
Time Frame:Up to 30 months
Safety Issue:
Description:To determine objective response rates (CR + PR). As described in the primary objective, formal disease assessments including imaging will be performed after cycles 3 and 6 of induction chemotherapy and every 4 cycles during the maintenance portion of treatment. Response and progression in cases of SLL will be evaluated using the International Working Group Criteria30 for response in lymphoma. Response and progression in cases of CLL will be evaluated in this study using the Revised IWCLL Criteria31 for response in CLL. Radiological methodologies, techniques and/or physical examination, established at baseline for the assessment and measurement of each identified lesion will be used for all subsequent assessments.
Measure:Toxicity
Time Frame:Up to 30 months
Safety Issue:
Description:• To determine toxicities observed with induction chemotherapy and maintenance therapy. Safety evaluations will be based on the incidence, intensity, and type of adverse events (AEs) and clinical laboratory results. Drug doses will be modified as required based on toxicity as assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0.
Measure:Time to Death
Time Frame:Up to 54 months
Safety Issue:
Description:• To determine overall survival. Overall survival will be determined from the date of enrollment until death from any cause.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Wisconsin, Madison

Trial Keywords

  • Lymphoid Leukemia
  • Bendamustine
  • Rituximab
  • Small Lymphocytic Lymphoma

Last Updated

January 24, 2017