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

Primary Purpose

Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Bendamustine
Rituximab
Lenalidomide
Sponsored by
University of Wisconsin, Madison
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Lymphocytic Leukemia focused on measuring CLL, SLL

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • St Vincent Regional Cancer Center
  • Bellin Memorial Hospital
  • Mercy Health System Heme/Onc
  • Gundersen Clinic
  • University of Wisconsin Carbone Cancer Center
  • Marshfield Clinic
  • Medical College of Wisconsin
  • Oconomowoc Memorial Hospital
  • Waukesha Memorial Hospital
  • Riverview Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Induction/Maintenance chemotherapy

Arm Description

Bendamustine + rituximab induction therapy followed by lenalidomide maintenance therapy

Outcomes

Primary Outcome Measures

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).
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.

Secondary Outcome Measures

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.
Toxicities Observed With Induction Chemotherapy and Maintenance Therapy
Toxicities were reported using the Common Terminology Criteria for Adverse Events, version 3.0.
Overall Survival
Overall survival (OS) is defined as the time from the day of first study drug administration until death from any cause.

Full Information

First Posted
September 9, 2009
Last Updated
November 14, 2019
Sponsor
University of Wisconsin, Madison
Collaborators
Celgene Corporation
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1. Study Identification

Unique Protocol Identification Number
NCT00974233
Brief Title
Study of Bendamustine/Rituxan Induction Chemotherapy With Revlimid Maintenance for Relapsed/Refractory CLL and SLL
Official Title
Phase II Study of Bendamustine and Rituximab Induction Chemoimmunotherapy With Maintenance Lenalidomide and Rituximab in Relapsed/Refractory CLL/SLL
Study Type
Interventional

2. Study Status

Record Verification Date
July 2017
Overall Recruitment Status
Completed
Study Start Date
October 2009 (undefined)
Primary Completion Date
July 2013 (Actual)
Study Completion Date
April 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Wisconsin, Madison
Collaborators
Celgene Corporation

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma
Keywords
CLL, SLL

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
34 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Induction/Maintenance chemotherapy
Arm Type
Experimental
Arm Description
Bendamustine + rituximab induction therapy followed by lenalidomide maintenance therapy
Intervention Type
Drug
Intervention Name(s)
Bendamustine
Other Intervention Name(s)
Treanda
Intervention Description
90 mg/m2/day IV days 1 and 2 every 28 days for 6 cycles
Intervention Type
Drug
Intervention Name(s)
Rituximab
Other Intervention Name(s)
rituxan
Intervention Description
375 mg/m2 Day 1 every 28 days for 6 cycles
Intervention Type
Drug
Intervention Name(s)
Lenalidomide
Other Intervention Name(s)
revlimid, CC-5013
Intervention Description
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.
Primary Outcome Measure Information:
Title
Progression Free Survival
Description
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).
Time Frame
42 months (6 months induction therapy, 12 months maintenance, 24 months long-term follow-up)
Title
Progression-free Survival
Description
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.
Time Frame
42 months (6 months induction therapy, 12 months maintenance, 24 months long-term follow-up)
Secondary Outcome Measure Information:
Title
Objective Response Rate (Complete + Partial Responses)
Description
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.
Time Frame
42 months (6 months induction therapy, 12 months maintenance, 24 months long-term follow-up)
Title
Toxicities Observed With Induction Chemotherapy and Maintenance Therapy
Description
Toxicities were reported using the Common Terminology Criteria for Adverse Events, version 3.0.
Time Frame
42 months (6 months induction therapy, 12 months maintenance, 24 months long-term follow-up)
Title
Overall Survival
Description
Overall survival (OS) is defined as the time from the day of first study drug administration until death from any cause.
Time Frame
42 months (6 months induction therapy, 12 months maintenance, 24 months long-term follow-up)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Julie Chang, MD
Organizational Affiliation
University of Wisconsin, Madison
Official's Role
Principal Investigator
Facility Information:
Facility Name
St Vincent Regional Cancer Center
City
Green Bay
State/Province
Wisconsin
ZIP/Postal Code
54301
Country
United States
Facility Name
Bellin Memorial Hospital
City
Green Bay
State/Province
Wisconsin
ZIP/Postal Code
54313
Country
United States
Facility Name
Mercy Health System Heme/Onc
City
Janesville
State/Province
Wisconsin
ZIP/Postal Code
53548
Country
United States
Facility Name
Gundersen Clinic
City
La Crosse
State/Province
Wisconsin
ZIP/Postal Code
54601
Country
United States
Facility Name
University of Wisconsin Carbone Cancer Center
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States
Facility Name
Marshfield Clinic
City
Marshfield
State/Province
Wisconsin
ZIP/Postal Code
54449
Country
United States
Facility Name
Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
Oconomowoc Memorial Hospital
City
Oconomowoc
State/Province
Wisconsin
ZIP/Postal Code
53066
Country
United States
Facility Name
Waukesha Memorial Hospital
City
Waukesha
State/Province
Wisconsin
ZIP/Postal Code
53188
Country
United States
Facility Name
Riverview Hospital
City
Wisconsin Rapids
State/Province
Wisconsin
ZIP/Postal Code
54494
Country
United States

12. IPD Sharing Statement

Links:
URL
https://cancer.wisc.edu/
Description
University of Wisconsin Carbone Cancer Center

Learn more about this trial

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

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