Study of Bendamustine/Rituxan Induction Chemotherapy With Revlimid Maintenance for Relapsed/Refractory CLL and SLL

Phase II Study of Bendamustine and Rituximab Induction Chemoimmunotherapy With Maintenance Lenalidomide and Rituximab in Relapsed/Refractory CLL/SLL

The purpose of this research is to evaluate a new combination of chemotherapy drugs for CLL/SLL using the drugs bendamustine (an intravenous chemotherapy drug), rituximab (an intravenous medication called a monoclonal antibody), and lenalidomide (an anti-cancer pill).

The purpose of this study is to see if giving the chemotherapy pill lenalidomide after treatment with bendamustine and rituximab is able to prolong the period of time before the cancer starts growing again and causing symptoms.

Study Overview

• Status: Completed
• Conditions: Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma
• Intervention / Treatment: Drug: Bendamustine; Drug: Rituximab; Drug: Lenalidomide

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Green Bay, Wisconsin, United States, 54301
      • St Vincent Regional Cancer Center
    • Green Bay, Wisconsin, United States, 54313
      • Bellin Memorial Hospital
    • Janesville, Wisconsin, United States, 53548
      • Mercy Health System Heme/Onc
    • La Crosse, Wisconsin, United States, 54601
      • Gundersen Clinic
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Carbone Cancer Center
    • Marshfield, Wisconsin, United States, 54449
      • Marshfield Clinic
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin
    • Oconomowoc, Wisconsin, United States, 53066
      • Oconomowoc Memorial Hospital
    • Waukesha, Wisconsin, United States, 53188
      • Waukesha Memorial Hospital
    • Wisconsin Rapids, Wisconsin, United States, 54494
      • Riverview Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically confirmed,CLL/SLL, documented relapsed or refractory disease after at least one prior chemotherapy regimen.
• In cases of SLL, patients must have at least one bidimensionally measurable lesion at least ≥1.5 cm measured in one dimension.
• ECOG performance status of 0-2 at study entry
• Laboratory test results within these ranges: ANC <=1500/μL, Platelet count <= 100,000/μL. Patients with ANC <1500/μL or plt <100,000/μL with splenomegaly or extensive bone marrow involvement as the etiology for their cytopenias are eligible.
• creatinine clearance of >60 mL/min as determined by the Cockcroft-Gault calculation.
• Total bilirubin <= 2X upper limit laboratory normal (ULN). Patients 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) <=5x 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).
• Patients may have received prior therapy with bendamustine or lenalidomide, but must not have disease that is refractory to bendamustine or lenalidomide.
• Prior therapy with rituximab is permitted, even in the setting of rituximab refractory disease.

Exclusion Criteria:

• Has received >5 lines of prior therapy for their disease. Re-treatment with an identical regimen does not count as a new regimen.
• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form or comply with the protocol treatment.
• Pregnant or breast feeding females. Lactating females must agree not to breast feed while taking lenalidomide.
• Prior history or current evidence of central nervous system or leptomeningeal involvement.
• Use of any other experimental drug or therapy within 28 days of baseline.
• Known hypersensitivity to thalidomide.
• The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
• Known to be positive for HIV or infectious hepatitis, type B or C.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Induction/Maintenance chemotherapy; Bendamustine + rituximab induction therapy followed by lenalidomide maintenance therapy	Drug: Bendamustine; 90 mg/m2/day IV days 1 and 2 every 28 days for 6 cycles; Other Names: Treanda; Drug: Rituximab; 375 mg/m2 Day 1 every 28 days for 6 cycles; Other Names: rituxan; Drug: Lenalidomide; 5 mg/day days 1-28 of each 28 day cycle, up to 12 cycles maximum. Dose escalation to 10 mg/day allowed after one cycle as defined in the protocol.; Other Names: CC-5013; revlimid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	The primary endpoint of this study was progression-free survival (PFS), defined as the number of days from the day of first study drug administration to the day the patient experienced disease progression or death from any cause. Response and progression in cases of small lymphocytic lymphoma(SLL) were evaluated using the International Working Group Criteria for response in NHL (Cheson, et al 1996). Response and progression in cases of chronic lymphocytic leukemia (CLL) were evaluated using the NCI-sponsored CLL Working Group guidelines for CLL (Cheson, et al 2007).	42 months (6 months induction therapy, 12 months maintenance, 24 months long-term follow-up)
Progression-free Survival	Progression-free survival (PFS) is defined as the time from the day of first study drug administration until progression of CLL/SLL or death from any cause. PFS is reported as the proportion of participants with PFS up to 42 months.	42 months (6 months induction therapy, 12 months maintenance, 24 months long-term follow-up)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (Complete + Partial Responses)	Response and progression in cases of SLL were evaluated using the International Working Group Criteria for response in NHL (Cheson, et al 1996). Response and progression in cases of CLL were evaluated using the NCI-sponsored CLL Working Group guidelines for CLL (Cheson, et al 2007). Complete response defined as resolution enlarged lymph nodes, spleen and liver; normalization of blood counts (neutrophils, hemoglobin, platelets); no residual CLL/SLL detectable in the bone marrow. Partial response defined as 50% or more reduction in size of enlarged lymph nodes, liver or spleen; 50% or more improvement of blood counts; 50% or more improvement in the blood lymphocyte count. Progressive disease defined as 50% or more increase in the combined measurements of at least 2 lymph nodes as measured on CT scans or the appearance of new enlarged lymph nodes; 50% of more increase in the size of the spleen or liver; 50% or more increase in blood lymphocyte count.	42 months (6 months induction therapy, 12 months maintenance, 24 months long-term follow-up)
Toxicities Observed With Induction Chemotherapy and Maintenance Therapy	Toxicities were reported using the Common Terminology Criteria for Adverse Events, version 3.0.	42 months (6 months induction therapy, 12 months maintenance, 24 months long-term follow-up)
Overall Survival	Overall survival (OS) is defined as the time from the day of first study drug administration until death from any cause.	42 months (6 months induction therapy, 12 months maintenance, 24 months long-term follow-up)

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Collaborators: Celgene Corporation

Publications and helpful links

Helpful Links

• University of Wisconsin Carbone Cancer Center

Study record dates

Study Major Dates

• Study Start: October 1, 2009
• Primary Completion (Actual): July 1, 2013
• Study Completion (Actual): April 1, 2015

Study Registration Dates

• First Submitted: September 9, 2009
• First Submitted That Met QC Criteria: September 9, 2009
• First Posted (Estimate): September 10, 2009

Study Record Updates

• Last Update Posted (Actual): December 2, 2019
• Last Update Submitted That Met QC Criteria: November 14, 2019
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: CLL; SLL
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia, Lymphoid; Leukemia; Leukemia, B-Cell; Leukemia, Lymphocytic, Chronic, B-Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Lenalidomide; Bendamustine Hydrochloride; Rituximab
• Other Study ID Numbers: HO08405; A534260 (Other Identifier: UW Madison); SMPH\MEDICINE\HEM-ONC (Other Identifier: UW Madison); RV-CLL/SLL-PI-397; H-2009-0087 (Other Identifier: Institutional Review Board); NCI-2011-00646 (Registry Identifier: NCI Trial ID)