Comment Period Extended to 3/23/2015 for Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Rituximab and Alemtuzumab in Treating Older Patients With Progressive Chronic Lymphocytic Leukemia

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier:
NCT01013961
First received: November 13, 2009
Last updated: February 9, 2015
Last verified: December 2012
  Purpose

RATIONALE: Monoclonal antibodies, such as rituximab and alemtuzumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer killing substances to them. Giving rituximab together with alemtuzumab may kill more cancer cells.

PURPOSE: This randomized phase II trial is studying two different doses of rituximab to compare how well they work when given together with alemtuzumab in treating older patients with progressive chronic lymphocytic leukemia.


Condition Intervention Phase
Leukemia
Biological: alemtuzumab
Biological: rituximab
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Primary Purpose: Treatment
Official Title: A Phase II Randomized Trial Comparing Standard and Low Dose Rituximab: Initial Treatment of Progressive Chronic Lymphocytic Leukemia in Elderly Patients Using Alemtuzumab, and Rituximab

Resource links provided by NLM:


Further study details as provided by Eastern Cooperative Oncology Group:

Primary Outcome Measures:
  • Rate of complete and overall response [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Toxicity as assessed by NCI CTC v4.0 criteria [ Designated as safety issue: Yes ]

Estimated Enrollment: 90
Study Start Date: October 2010
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive alemtuzumab subcutaneously (SC) on days 1-3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27, 29, and 31 and standard-dose rituximab IV on days 8, 15, 22, and 29 in course 1. In courses 2 and 3, patients receive alemtuzumab SC on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26 and standard-dose rituximab IV on days 3, 10, 17, and 24. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
Biological: alemtuzumab
Given IV
Biological: rituximab
Given IV
Experimental: Arm II
Patients receive alemtuzumab as in arm I. Patients also receive low-dose rituximab IV on days 6, 8, 10, 13, 15, 17, 20, 22, 24, 27, 29, and 31 in course 1 and on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26 in courses 2 and 3. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
Biological: alemtuzumab
Given IV
Biological: rituximab
Given IV

Detailed Description:

OBJECTIVES:

Primary

  • To compare the rate of complete and overall response in elderly patients with progressive chronic lymphocytic leukemia (CLL) treated with one of two doses of rituximab combined with alemtuzumab to determine if the use of modified-dose rituximab significantly affects outcome.

Secondary

  • To monitor and assess toxicity of these regimens.
  • To determine the overall and progression-free survival, time to clinical response, time to next treatment, and duration of response in patients treated with these regimens
  • To assess the correlation between risk stratification prognostic markers (i.e., CD38, ZAP-70, FISH, and IgVH mutation) and clinical outcome.
  • To assess response to these regimens using both the NCI-WG 96 criteria and an expanded definition of response for patients in complete remission, including immunohistochemical examination of the bone marrow and sensitive flow cytometry (4-6 color) of blood for minimal residual disease and CT scans for residual adenopathy.
  • To determine the mechanism of action of rituximab and alemtuzumab and to determine mechanisms of resistance of a subpopulation of CLL cells to these drugs.

OUTLINE: This is a multicenter study. Patients are stratified according to FISH risk (low [13q14-] vs intermediate [12+, no abnormality, all other abnormalities] vs high [17p13-,11q22-]). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive alemtuzumab subcutaneously (SC) on days 1-3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27, 29, and 31 and standard-dose rituximab IV on days 8, 15, 22, and 29 in course 1. In courses 2 and 3, patients receive alemtuzumab SC on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26 and standard-dose rituximab IV on days 3, 10, 17, and 24. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
  • Arm II: Patients receive alemtuzumab as in arm I. Patients also receive low-dose rituximab IV on days 6, 8, 10, 13, 15, 17, 20, 22, 24, 27, 29, and 31 in course 1 and on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26 in courses 2 and 3. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

Blood and bone marrow samples are collected periodically for cytogenetic and biomarker analysis.

After completion of study therapy, patients are followed up periodically for 5 years.

  Eligibility

Ages Eligible for Study:   65 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of chronic lymphocytic leukemia (CLL) meeting the following criteria:

    • Minimum threshold peripheral lymphocyte count of 5 x 10^9/L (CLL variant) OR palpable adenopathy > 1 cm or palpable splenomegaly (SLL variant)
    • Immunophenotypic demonstrations of a population of B-lymphocytes (as defined by CD19+) that are monoclonal (by light-chain exclusion) AND have ≥ 3 of the following characteristics:

      • CD5+
      • CD23+
      • Dim surface light chain expression
      • Dim surface CD20 expression
    • FISH analysis is negative for IGH/CCND1 and/or immunostaining is negative for cyclin D1 expression (to exclude mantle cell lymphoma)
  • Has progressive, symptomatic CLL, defined by at least one of the following:

    • Weight loss > 10% within the past 6 months attributable to progressive CLL (grade 2 or higher)
    • Extreme fatigue attributable to progressive CLL (grade 3 or higher)
    • Fevers > 100.5° F for 2 weeks without evidence of infection (grade 1 or higher)
    • Night sweats without evidence of infection (drenching)
    • Evidence of progressive bone marrow failure with hemoglobin < 11 g/dL or platelet count < 100 x 10^9/L
    • Rapidly progressive lymphadenopathy for which the largest node is ≤ 5 cm in any dimension

      • Largest lymph nodes involved in the neck, axilla, and groin need to be measured and followed for response
  • No massive splenomegaly > 6 cm below left costal margin, at rest, on clinical examination
  • No lymphadenopathy > 5 cm in any diameter

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-3
  • Creatinine ≤ 2 times upper limit of normal (ULN)
  • Total bilirubin ≤ 1.5 times ULN
  • AST ≤ 3.0 times ULN (unless due to CLL involvement of the liver)
  • Not pregnant or nursing
  • Fertile patients must use effective contraception during and for 12 months after completion of study therapy
  • None of the following comorbid conditions:

    • New York Heart Association class III or IV heart disease
    • Recent myocardial infarction (within the past month)
    • Uncontrolled infection
    • HIV/AIDS
    • Serological evidence of active hepatitis B infection (HBsAg or HBeAg positive)
    • Positive hepatitis C serology
  • No active autoimmune hemolytic anemia, immune thrombocytopenia, or pure red blood cell aplasia
  • No other active primary malignancy requiring treatment or that limits survival to ≤ 2 years, except for in situ carcinoma of the cervix or breast or non-metastatic basal cell or squamous cell carcinoma of the skin

PRIOR CONCURRENT THERAPY:

  • No prior treatment for CLL
  • More than 4 weeks since prior major surgery
  • No concurrent continuous systemic corticosteroids

    • Prior corticosteroids are allowed but not at time of pre-registration to the study
  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: NCT01013961

  Hide Study Locations
Locations
United States, Arizona
Mayo Clinic Scottsdale
Scottsdale, Arizona, United States, 85259-5499
United States, Florida
Michael and Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital
Fort Lauderdale, Florida, United States, 33308
Ella Milbank Foshay Cancer Center at Jupiter Medical Center
Jupiter, Florida, United States, 33458
CCOP - Mount Sinai Medical Center
Miami Beach, Florida, United States, 33140
United States, Georgia
Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/Candler
Savannah, Georgia, United States, 31405
United States, Illinois
Rush-Copley Cancer Care Center
Aurora, Illinois, United States, 60504
St. Joseph Medical Center
Bloomington, Illinois, United States, 61701
Illinois CancerCare - Bloomington
Bloomington%, Illinois, United States, 61701
Graham Hospital
Canton, Illinois, United States, 61520
Illinois CancerCare - Canton
Canton, Illinois, United States, 61520
Illinois CancerCare - Carthage
Carthage, Illinois, United States, 62321
Memorial Hospital
Carthage, Illinois, United States, 62321
University of Chicago Cancer Research Center
Chicago, Illinois, United States, 60637-1470
Illinois CancerCare - Eureka
Eureka, Illinois, United States, 61530
Eureka Community Hospital
Eureka, Illinois, United States, 61530
Galesburg Clinic, PC
Galesburg, Illinois, United States, 61401
Illinois CancerCare - Havana
Havana, Illinois, United States, 62644
Illinois CancerCare - Kewanee Clinic
Kewanee, Illinois, United States, 61443
Illinois CancerCare - Macomb
Macomb, Illinois, United States, 61455
McDonough District Hospital
Macomb, Illinois, United States, 61455
Illinois CancerCare - Monmouth
Monmouth, Illinois, United States, 61462
OSF Holy Family Medical Center
Monmouth, Illinois, United States, 61462
BroMenn Regional Medical Center
Normal, Illinois, United States, 61761
Community Cancer Center
Normal, Illinois, United States, 61761
Illinois CancerCare - Community Cancer Center
Normal, Illinois, United States, 61761
Community Hospital of Ottawa
Ottawa, Illinois, United States, 61350
Oncology Hematology Associates of Central Illinois, PC - Ottawa
Ottawa, Illinois, United States, 61350
Illinois CancerCare - Pekin
Pekin, Illinois, United States, 61603
Cancer Treatment Center at Pekin Hospital
Pekin, Illinois, United States, 61554
CCOP - Illinois Oncology Research Association
Peoria, Illinois, United States, 61615
Methodist Medical Center of Illinois
Peoria, Illinois, United States, 61636
Oncology Hematology Associates of Central Illinois, PC - Peoria
Peoria, Illinois, United States, 61615
OSF St. Francis Medical Center
Peoria, Illinois, United States, 61637
Proctor Hospital
Peoria, Illinois, United States, 61614
Illinois CancerCare - Peru
Peru, Illinois, United States, 61354
Illinois Valley Community Hospital
Peru, Illinois, United States, 61354
Illinois CancerCare - Princeton
Princeton, Illinois, United States, 61356
Swedish-American Regional Cancer Center
Rockford, Illinois, United States, 61104-2315
Illinois CancerCare - Spring Valley
Spring Valley, Illinois, United States, 61362
CCOP - Carle Cancer Center
Urbana, Illinois, United States, 61801
United States, Indiana
St. Francis Hospital and Health Centers - Beech Grove Campus
Beech Grove, Indiana, United States, 46107
Reid Hospital & Health Care Services
Richmond, Indiana, United States, 47374
United States, Iowa
McFarland Clinic, PC
Ames, Iowa, United States, 50010
Cedar Rapids Oncology Associates
Cedar Rapids, Iowa, United States, 52403
Mercy Regional Cancer Center at Mercy Medical Center
Cedar Rapids, Iowa, United States, 52403
Mercy Cancer Center at Mercy Medical Center - North Iowa
Mason City, Iowa, United States, 50401
Siouxland Hematology-Oncology Associates, LLP
Sioux City, Iowa, United States, 51101
St. Luke's Regional Medical Center
Sioux City, Iowa, United States, 51104
Mercy Medical Center - Sioux City
Sioux City, Iowa, United States, 51102
United States, Louisiana
Tulane Cancer Center Office of Clinical Research
Alexandria, Louisiana, United States, 71315-3198
Hematology-Oncology Clinic
Baton Rouge, Louisiana, United States, 70809
Feist-Weiller Cancer Center at Louisiana State University Health Sciences
Shreveport, Louisiana, United States, 71130-3932
United States, Michigan
West Michigan Cancer Center
Kalamazoo, Michigan, United States, 49007-3731
Borgess Medical Center
Kalamazoo, Michigan, United States, 49001
Bronson Methodist Hospital
Kalamazoo, Michigan, United States, 49007
Upper Michigan Cancer Center at Marquette General Hospital
Marquette, Michigan, United States, 49855
United States, Minnesota
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
United States, Missouri
Central Care Cancer Center at Carrie J. Babb Cancer Center
Bolivar, Missouri, United States, 65613
Skaggs Cancer Center at Skaggs Regional Medical Center
Branson, Missouri, United States, 65616
Southeast Cancer Center
Cape Girardeau, Missouri, United States, 63703
Goldschmidt Cancer Center
Jefferson City, Missouri, United States, 65109
Mercy Clinic Cancer and Hematology - Rolla
Rolla, Missouri, United States, 65401
Phelps County Regional Medical Center
Rolla, Missouri, United States, 65401
Missouri Baptist Cancer Center
Saint Louis, Missouri, United States, 63131
CCOP - Cancer Research for the Ozarks
Springfield, Missouri, United States, 65802
Hulston Cancer Center at Cox Medical Center South
Springfield, Missouri, United States, 65807
St. John's Regional Health Center
Springfield, Missouri, United States, 65804
United States, Nevada
CCOP - Nevada Cancer Research Foundation
Las Vegas, Nevada, United States, 89106
United States, North Carolina
Randolph Hospital
Asheboro, North Carolina, United States, 27203-5400
Wayne Memorial Hospital, Incorporated
Goldsboro, North Carolina, United States, 27534
Moses Cone Regional Cancer Center at Wesley Long Community Hospital
Greensboro, North Carolina, United States, 27403-1198
Pardee Memorial Hospital
Hendersonville, North Carolina, United States, 28791
Kinston Medical Specialists
Kinston, North Carolina, United States, 28501
Annie Penn Cancer Center
Reidsville, North Carolina, United States, 27320
Iredell Memorial Hospital
Statesville, North Carolina, United States, 28677
United States, North Dakota
Medcenter One Hospital Cancer Care Center
Bismarck, North Dakota, United States, 58501
Mid Dakota Clinic, PC
Bismarck, North Dakota, United States, 58501
St. Alexius Medical Center Cancer Center
Bismarck, North Dakota, United States, 58502
United States, Ohio
Aultman Cancer Center at Aultman Hospital
Canton, Ohio, United States, 44710-1799
CCOP - Dayton
Dayton, Ohio, United States, 45420
David L. Rike Cancer Center at Miami Valley Hospital
Dayton, Ohio, United States, 45409
Good Samaritan Hospital
Dayton, Ohio, United States, 45406
Grandview Hospital
Dayton, Ohio, United States, 45405
Samaritan North Cancer Care Center
Dayton, Ohio, United States, 45415
Blanchard Valley Medical Associates
Findlay, Ohio, United States, 45840
Middletown Regional Hospital
Franklin, Ohio, United States, 45005-1066
Wayne Hospital
Greenville, Ohio, United States, 45331
Charles F. Kettering Memorial Hospital
Kettering, Ohio, United States, 45429
St. Rita's Medical Center
Lima, Ohio, United States, 45801
UVMC Cancer Care Center at Upper Valley Medical Center
Troy, Ohio, United States, 45373-1300
Ruth G. McMillan Cancer Center at Greene Memorial Hospital
Xenia, Ohio, United States, 45385
United States, Pennsylvania
Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033-0850
Lewistown Hospital
Lewistown, Pennsylvania, United States, 17044
Hematology and Oncology Associates of Northeastern Pennsylvania
Scranton, Pennsylvania, United States, 18510
Mercy Hospital Cancer Center - Scranton
Scranton, Pennsylvania, United States, 18501
Mount Nittany Medical Center
State College, Pennsylvania, United States, 16803
United States, Tennessee
U.T. Medical Center Cancer Institute
Knoxville, Tennessee, United States, 37920-6999
United States, Virginia
Danville Regional Medical Center
Danville, Virginia, United States, 24541
United States, Wisconsin
UW Cancer Center Johnson Creek
Johnson Creek, Wisconsin, United States, 53038
Gundersen Lutheran Center for Cancer and Blood
La Crosse, Wisconsin, United States, 54601
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
Madison, Wisconsin, United States, 53792-6164
Riverview UW Cancer Center at Riverview Hospital
Wisconsin Rapids, Wisconsin, United States, 54494
Sponsors and Collaborators
Eastern Cooperative Oncology Group
Investigators
Study Chair: Clive S. Zent, MD Mayo Clinic
  More Information

Additional Information:
No publications provided

Responsible Party: Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier: NCT01013961     History of Changes
Other Study ID Numbers: CDR0000659098, ECOG-E1908
Study First Received: November 13, 2009
Last Updated: February 9, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Eastern Cooperative Oncology Group:
B-cell chronic lymphocytic leukemia
stage I chronic lymphocytic leukemia
stage II chronic lymphocytic leukemia
stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Immune System Diseases
Immunoproliferative Disorders
Leukemia, B-Cell
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Alemtuzumab
Rituximab
Antineoplastic Agents
Antirheumatic Agents
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on March 03, 2015