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)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by University of Wisconsin, Madison
Sponsor:
Collaborators:
Celgene Corporation
Genentech, Inc.
Information provided by (Responsible Party):
University of Wisconsin, Madison
ClinicalTrials.gov Identifier:
NCT01754857
First received: November 9, 2012
Last updated: May 29, 2014
Last verified: May 2014
  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.


Condition Intervention Phase
Chronic Lymphocytic Leukemia (CLL)
Small Lymphocytic Lymphoma (SLL)
Drug: Bendamustine and Rituximab induction with Rituximab and Lenalidomide Maintenance
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by University of Wisconsin, Madison:

Primary Outcome Measures:
  • Time to progression [ Time Frame: Up to 30 months ] [ Designated as safety issue: No ]
    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:
  • Objective Response Rates [ Time Frame: Up to 30 months ] [ Designated as safety issue: No ]
    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.

  • Toxicity [ Time Frame: Up to 30 months ] [ Designated as safety issue: Yes ]
    • 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.

  • Time to Death [ Time Frame: Up to 54 months ] [ Designated as safety issue: No ]
    • To determine overall survival. Overall survival will be determined from the date of enrollment until death from any cause.


Estimated Enrollment: 32
Study Start Date: November 2013
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bendamustine + Rituximab-->Rituximab and Lenalidomide

Induction chemoimmunotherapy with bendamustine 90 mg/m2/day IV days 1 & 2 and rituximab 500 mg/m2 day 1 (375 mg/m2 cycle 1)every 28 days for 6 cycles.

Rituximab maintenance 375 mg/m2 IV on day 1 of odd-numbered 28 day cycles for a total of 12 doses. Lenalidomide maintenance administered as 5 mg/day on days 1-28 of cycles 1-24 (28-day cycles), with dose escalation up to 10 mg/day allowed.

Drug: Bendamustine and Rituximab induction with Rituximab and Lenalidomide Maintenance

  Eligibility

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

Inclusion Criteria:

  1. Histologically confirmed CLL/SLL.
  2. No prior cytotoxic chemotherapy for their disease; prior therapy with single-agent rituximab is permitted.
  3. Understand and voluntarily sign an informed consent document.
  4. At least 18 years at the time of signing the informed consent document.
  5. In cases of SLL, subjects must have at least one bidimensionally measurable lesion at least ≥1.5 cm measured in one dimension.
  6. ECOG performance status of less than or equal to 2 at study entry
  7. Laboratory test results within these ranges:

    • Absolute neutrophil count greater than or equal to 1500/μL
    • Platelet count greater than or equal to 100,000/μL
    • Subjects with neutrophils <1500/μL or platelets <100,000/μL 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 less than or equal to 2X 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 AST (SGOT) and ALT (SGPT) less than or equal to 5X ULN
    • Serum alkaline phosphatase ≤5X ULN
  8. 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).
  9. Life expectancy of at least 3 months.
  10. All study participants must be willing to be registered into the mandatory Revlamin REMS program®, and be willing and able to comply with the requirements of REMS program®.
  11. Subjects must not have a known history of hypersensitivity to mannitol.
  12. Prior therapy with rituximab is permitted, even in the setting of rituximab-refractory disease.
  13. 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.
  14. 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 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.

13. Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS® program. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy. See Appendix: Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods.

Exclusion Criteria:

  1. 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.
  2. Pregnant or breast-feeding females. Lactating females must agree not to breast-feed while taking lenalidomide.
  3. 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.
  4. Subjects are not eligible if there is a prior history or current evidence of central nervous system or leptomeningeal involvement.
  5. Known hypersensitivity to thalidomide.
  6. Concurrent use of other anti-cancer agents or treatments.
  7. Known to be positive for HIV or infectious hepatitis (type B or C).
  8. 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.
  9. Severe or life-threatening anaphylaxis or hypersensitivity reaction when previously exposed to rituximab or other monoclonal antibody therapy.
  10. Chronic hepatitis B or hepatitis C infection.
  11. New York Heart Association class 3-4 heart failure.
  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: NCT01754857

Contacts
Contact: Julie Chang, MD 608-263-1836 jc2@medicine.wisc.edu

Locations
United States, Wisconsin
University of Wisconsin Recruiting
Madison, Wisconsin, United States, 53792
Contact: Julie Chang, MD    608-263-1836    jc2@medicine.wisc.edu   
Contact: Elaine Paterson, PhD    608-262-7202    epaterso@uwcarbone.wisc.edu   
Sponsors and Collaborators
University of Wisconsin, Madison
Celgene Corporation
Genentech, Inc.
Investigators
Principal Investigator: Julie Chang, MD University of Wisconsin, Madison
  More Information

No publications provided

Responsible Party: University of Wisconsin, Madison
ClinicalTrials.gov Identifier: NCT01754857     History of Changes
Other Study ID Numbers: HO11414
Study First Received: November 9, 2012
Last Updated: May 29, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Wisconsin, Madison:
CLL
SLL

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Lymphoma
Immune System Diseases
Immunoproliferative Disorders
Leukemia, B-Cell
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Bendamustine
Lenalidomide
Nitrogen Mustard Compounds
Rituximab
Thalidomide
Alkylating Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Growth Inhibitors
Growth Substances
Immunologic Factors
Immunosuppressive Agents
Leprostatic Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 23, 2014