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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


Phase 2
65 Years
N/A
Open (Enrolling)
Both
Leukemia

Thank you

Trial Information

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


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Primary Purpose: Treatment

Outcome Measure:

Rate of complete and overall response

Safety Issue:

No

Principal Investigator

Clive S. Zent, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Mayo Clinic

Authority:

Unspecified

Study ID:

CDR0000659098

NCT ID:

NCT01013961

Start Date:

October 2010

Completion Date:

Related Keywords:

  • Leukemia
  • 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
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid

Name

Location

Mayo Clinic ScottsdaleScottsdale, Arizona  85259
Mayo Clinic Cancer CenterRochester, Minnesota  55905
University of Chicago Cancer Research CenterChicago, Illinois  60637
CCOP - Mount Sinai Medical CenterMiami Beach, Florida  33140
CCOP - Illinois Oncology Research AssociationPeoria, Illinois  61602
CCOP - Carle Cancer CenterUrbana, Illinois  61801
Rush-Copley Cancer Care CenterAurora, Illinois  60507
Cedar Rapids Oncology AssociatesCedar Rapids, Iowa  52403
Mercy Medical Center - Sioux CitySioux City, Iowa  51104
Siouxland Hematology-Oncology Associates, LLPSioux City, Iowa  51101
St. Luke's Regional Medical CenterSioux City, Iowa  51104
Bronson Methodist HospitalKalamazoo, Michigan  49007
West Michigan Cancer CenterKalamazoo, Michigan  49007-3731
Borgess Medical CenterKalamazooaa, Michigan  49001
Aultman Cancer Center at Aultman HospitalCanton, Ohio  44710-1799
St. Rita's Medical CenterLima, Ohio  45801
University of Wisconsin Paul P. Carbone Comprehensive Cancer CenterMadison, Wisconsin  53792-6164
Methodist Medical Center of IllinoisPeoria, Illinois  61636
CCOP - Cancer Research for the OzarksSpringfield, Missouri  65807
CCOP - DaytonKettering, Ohio  45429
Mercy Hospital Cancer Center - ScrantonScranton, Pennsylvania  18501
Hulston Cancer Center at Cox Medical Center SouthSpringfield, Missouri  65807
St. John's Regional Health CenterSpringfield, Missouri  65804
Lewistown HospitalLewistown, Pennsylvania  17044
Mount Nittany Medical CenterState College, Pennsylvania  16803
Wayne Memorial Hospital, IncorporatedGoldsboro, North Carolina  27534
Swedish-American Regional Cancer CenterRockford, Illinois  61104-2315
Tulane Cancer Center Office of Clinical ResearchAlexandria, Louisiana  71315-3198
CCOP - Nevada Cancer Research FoundationLas Vegas, Nevada  89109-2306
Gundersen Lutheran Center for Cancer and BloodLa Crosse, Wisconsin  54601
Ella Milbank Foshay Cancer Center at Jupiter Medical CenterJupiter, Florida  33458
St. Joseph Medical CenterBloomington, Illinois  61701
Graham HospitalCanton, Illinois  61520
Memorial HospitalCarthage, Illinois  62321
Eureka Community HospitalEureka, Illinois  61530
McDonough District HospitalMacomb, Illinois  61455
BroMenn Regional Medical CenterNormal, Illinois  61761
Community Cancer CenterNormal, Illinois  61761
Community Hospital of OttawaOttawa, Illinois  61350
Oncology Hematology Associates of Central Illinois, PC - OttawaOttawa, Illinois  61350
Cancer Treatment Center at Pekin HospitalPekin, Illinois  61554
Oncology Hematology Associates of Central Illinois, PC - PeoriaPeoria, Illinois  61615
OSF St. Francis Medical CenterPeoria, Illinois  61637
Proctor HospitalPeoria, Illinois  61614
Illinois Valley Community HospitalPeru, Illinois  61354
St. Francis Hospital and Health Centers - Beech Grove CampusBeech Grove, Indiana  46107
Mercy Regional Cancer Center at Mercy Medical CenterCedar Rapids, Iowa  52403
Feist-Weiller Cancer Center at Louisiana State University Health SciencesShreveport, Louisiana  71130-3932
Upper Michigan Cancer Center at Marquette General HospitalMarquette, Michigan  49855
Iredell Memorial HospitalStatesville, North Carolina  28677
Samaritan North Cancer Care CenterDayton, Ohio  45415
Grandview HospitalDayton, Ohio  45405
David L. Rike Cancer Center at Miami Valley HospitalDayton, Ohio  45409
Good Samaritan HospitalDayton, Ohio  45406
Blanchard Valley Medical AssociatesFindlay, Ohio  45840
Charles F. Kettering Memorial HospitalKettering, Ohio  45429
Middletown Regional HospitalMiddletown, Ohio  45044
UVMC Cancer Care Center at Upper Valley Medical CenterTroy, Ohio  45373-1300
Ruth G. McMillan Cancer Center at Greene Memorial HospitalXenia, Ohio  45385
Danville Regional Medical CenterDanville, Virginia  24541
Mercy Cancer Center at Mercy Medical Center - North IowaMason City, Iowa  50401
Missouri Baptist Cancer CenterSt. Louis, Missouri  63131
Randolph HospitalAsheboro, North Carolina  27203
Moses Cone Regional Cancer Center at Wesley Long Community HospitalGreensboro, North Carolina  27401
Annie Penn Cancer CenterReidsville, North Carolina  27320
Michael and Dianne Bienes Comprehensive Cancer Center at Holy Cross HospitalFort Lauderdale, Florida  33308
Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/CandlerSavannah, Georgia  31405
Reid Hospital & Health Care ServicesRichmond, Indiana  47374
McFarland Clinic, PCAmes, Iowa  50010
Wayne HospitalGreenville, Ohio  45331
Penn State Hershey Cancer Institute at Milton S. Hershey Medical CenterHershey, Pennsylvania  17033-0850
Hematology and Oncology Associates of Northeastern PennsylvaniaScranton, Pennsylvania  18510
UW Cancer Center Johnson CreekJohnson Creek, Wisconsin  53038
Mid Dakota Clinic, PCBismarck, North Dakota  58501
Pardee Memorial HospitalHendersonville, North Carolina  28791
Kinston Medical SpecialistsKinston, North Carolina  28501
Phelps County Regional Medical CenterRolla, Missouri  65401
Galesburg Clinic, PCGalesburg, Illinois  61401
Illinois CancerCare - BloomingtonBloomington%, Illinois  61701
Illinois CancerCare - CantonCanton, Illinois  61520
Illinois CancerCare - CarthageCarthage, Illinois  62321
Illinois CancerCare - EurekaEureka, Illinois  61530
Illinois CancerCare - HavanaHavana, Illinois  62644
Illinois CancerCare - Kewanee ClinicKewanee, Illinois  61443
Illinois CancerCare - MacombMacomb, Illinois  61455
OSF Holy Family Medical CenterMonmouth, Illinois  61462
Illinois CancerCare - MonmouthMonmouth, Illinois  61462
Illinois CancerCare - Community Cancer CenterNormal, Illinois  61761
Illinois CancerCare - PekinPekin, Illinois  61603
Illinois CancerCare - PeruPeru, Illinois  61354
Illinois CancerCare - PrincetonPrinceton, Illinois  61356
Illinois CancerCare - Spring ValleySpring Valley, Illinois  61362
U.T. Medical Center Cancer InstituteKnoxville, Tennessee  37920-6999
Medcenter One Hospital Cancer Care CenterBismarck, North Dakota  58501
St. Alexius Medical Center Cancer CenterBismarck, North Dakota  58502
Hematology-Oncology ClinicBaton Rouge, Louisiana  70808
Skaggs Cancer Center at Skaggs Regional Medical CenterBranson, Missouri  65616
Southeast Cancer CenterCape Girardeau, Missouri  63703
Goldschmidt Cancer CenterJefferson City, Missouri  65109
Riverview UW Cancer Center at Riverview HospitalWisconsin Rapids, Wisconsin  54494
Central Care Cancer Center at Carrie J. Babb Cancer CenterBolivar, Missouri  65613
Mercy Clinic Cancer and Hematology - RollaRolla, Missouri  65401