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

Phase 2

Completed

• Conditions: Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma
• Interventions: Drug: Bendamustine; Drug: Rituximab; Drug: Lenalidomide

• Registration Number: NCT00974233
• Lead Sponsor: University of Wisconsin, Madison

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2009-09-09
• Study First Submitted QC: 2009-09-09
• Study First Posted: 2009-09-10
• Study Start: 2009-10
• Primary Completion: 2013-07
• Study Completion: 2015-04
• Results First Submitted: 2016-05-17
• Status Verified: 2017-07
• Results First Submitted QC: 2017-07-12
• Results First Posted: 2017-07-13
• Last Update Submitted: 2019-11-14
• Last Update Posted: 2019-12-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 34

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Induction/Maintenance chemotherapy	Lenalidomide	Bendamustine + rituximab induction therapy followed by lenalidomide maintenance therapy
Induction/Maintenance chemotherapy	Bendamustine	Bendamustine + rituximab induction therapy followed by lenalidomide maintenance therapy
Induction/Maintenance chemotherapy	Rituximab	Bendamustine + rituximab induction therapy followed by lenalidomide maintenance therapy

Primary Outcome Measures

Name	Time	Method
Progression Free Survival	42 months (6 months induction therapy, 12 months maintenance, 24 months long-term follow-up)	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).
Progression-free Survival	42 months (6 months induction therapy, 12 months maintenance, 24 months long-term follow-up)	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.

Secondary Outcome Measures

Name	Time	Method
Overall Survival	42 months (6 months induction therapy, 12 months maintenance, 24 months long-term follow-up)	Overall survival (OS) is defined as the time from the day of first study drug administration until death from any cause.
Objective Response Rate (Complete + Partial Responses)	42 months (6 months induction therapy, 12 months maintenance, 24 months long-term follow-up)	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.
Toxicities Observed With Induction Chemotherapy and Maintenance Therapy	42 months (6 months induction therapy, 12 months maintenance, 24 months long-term follow-up)	Toxicities were reported using the Common Terminology Criteria for Adverse Events, version 3.0.

Trial Locations

Locations (10)

Oconomowoc Memorial Hospital; 🇺🇸 Oconomowoc, Wisconsin, United States

Gundersen Clinic; 🇺🇸 La Crosse, Wisconsin, United States

University of Wisconsin Carbone Cancer Center; 🇺🇸 Madison, Wisconsin, United States

Marshfield Clinic; 🇺🇸 Marshfield, Wisconsin, United States

Waukesha Memorial Hospital; 🇺🇸 Waukesha, Wisconsin, United States

Riverview Hospital; 🇺🇸 Wisconsin Rapids, Wisconsin, United States

Medical College of Wisconsin; 🇺🇸 Milwaukee, Wisconsin, United States

Bellin Memorial Hospital; 🇺🇸 Green Bay, Wisconsin, United States

Mercy Health System Heme/Onc; 🇺🇸 Janesville, Wisconsin, United States

St Vincent Regional Cancer Center; 🇺🇸 Green Bay, Wisconsin, United States