Trial record 2 of 2 for:    CONNECT CLL

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT01754857
Recruitment Status : Recruiting
First Posted : December 21, 2012
Last Update Posted : October 4, 2017
Celgene Corporation
Genentech, Inc.
Information provided by (Responsible Party):
University of Wisconsin, Madison

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Lymphoid Leukemia Small Lymphocytic Lymphoma Lymphoma, Non-Hodgkin Drug: Bendamustine Drug: Rituximab Drug: Lenalidomide Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 32 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of Bendamustine and Rituximab Induction Chemoimmunotherapy Followed by Maintenance Rituximab and Lenalidomide in Previously Untreated Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL)
Study Start Date : November 2013
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : November 2021

Arm Intervention/treatment
Experimental: Bendamustine, rituximab, lenalidomide

INDUCTION: Bendamustine 90 mg/m2 IV D1&2 and rituximab IV D1 (up to day 5 of course 1 only) every 28 days for 6 treatment cycles. Patients achieving objective response 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: Beginning 6-12 weeks after completion of induction therapy, patients receive rituximab IV on day 1 of every odd-numbered cycle for 24 cycles; lenalidomide 5-10 mg PO daily on days 1-28 of each cycle (28 day cycles). Patients experiencing excessive toxicity from lenalidomide may continue maintenance therapy with rituximab alone.

Drug: Bendamustine
Given IV
Drug: Rituximab
Given IV
Drug: Lenalidomide
Given PO

Primary Outcome Measures :
  1. Time to progression [ Time Frame: Up to 30 months ]
    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 :
  1. Objective Response Rates [ Time Frame: Up to 30 months ]
    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.

  2. Toxicity [ Time Frame: Up to 30 months ]
    • 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.

  3. Time to Death [ Time Frame: Up to 54 months ]
    • To determine overall survival. Overall survival will be determined from the date of enrollment until death from any cause.

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01754857

Contact: Cancer Connect (800) 622-8922

United States, Wisconsin
University of Wisconsin Recruiting
Madison, Wisconsin, United States, 53792
Contact: Julie Chang, MD    608-263-1836   
Contact: Erica Stubbendick    608-263-2944   
Sponsors and Collaborators
University of Wisconsin, Madison
Celgene Corporation
Genentech, Inc.
Principal Investigator: Julie Chang, MD University of Wisconsin, Madison

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: University of Wisconsin, Madison Identifier: NCT01754857     History of Changes
Other Study ID Numbers: HO11414
2017-0072 ( Other Identifier: HS IRB Number )
First Posted: December 21, 2012    Key Record Dates
Last Update Posted: October 4, 2017
Last Verified: October 2017

Keywords provided by University of Wisconsin, Madison:
Lymphoid Leukemia
Small Lymphocytic Lymphoma

Additional relevant MeSH terms:
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Non-Hodgkin
Leukemia, Lymphoid
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Bendamustine Hydrochloride
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Immunosuppressive Agents
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antineoplastic Agents, Alkylating
Alkylating Agents