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

NCT01013961 | Terminated Phase 2 Results DMC

• 2 other identifiers: E1908U10CA180794
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 102

Brief Summary

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.

Conditions

Chronic Lymphocytic Leukemia

Keywords

chronic lymphocytic leukemia; small lymphocytic lymphoma; CLL; elderly; low dose rituximab; alemtuzumab; monoclonal antibodies

Outcome Measures

Primary Outcomes (2)

• Proportion of Patients With Complete Response (CR)

  Response was evaluated using NCI-WG96 criteria. A CR requires all of the following for \>= 2 months: * Absence of lymphadenopathy \> 1 cm in diameter by physical examination * No hepatomegaly or splenomegaly on physical exam * No constitutional symptoms * Normal complete blood count (CBC) * Patients achieving a clinical CR with negative CT scan after 2 cycles of therapy are re-evaluated using immunohistochemical examination of bone marrow biopsy for residual CLL cells. Patients with no evidence of residual disease and no radiological evidence of residual CLL on CT scan of chest-abdomen-pelvis and no clinical evidence of CLL on clinical evaluation after completion of 2 cycles of therapy will be considered to have a CR with no evidence of residual disease

  Assessed after 2 cycles of treatment and 2 months after completion of therapy

• Proportion of Patients With Overall Response (OR)

  OR is defined as either CR, clinical CR, or partial response (PR) evaluated by NCI-WG96 criteria. CR has been defined in the other primary endpoint. A clinical CR requires all of the following: * Absence of lymphadenopathy by physical examination * No hepatomegaly or splenomegaly. Spleen and/or liver, if considered enlarged at baseline, should not be palpable, due to disease, on physical exam * Absence of constitutional symptoms * Normal CBC as exhibited by: A PR requires all the following for ≥2 months: * ≥50% decrease in peripheral blood lymphocyte count from baseline * ≥50% reduction in lymphadenopathy * ≥50% reduction in size of liver and/or spleen * Polymorphonuclear leukocytes ≥1.5x10\^9/L or 50% improvement over baseline * Platelets \>100x10\^9/L or 50% improvement over baseline * Hemoglobin \>11.0 gm/dl or 50% improvement over baseline without transfusions * Any constitutional symptoms

  Assessed after 2 cycles of treatment and 2 months after completion of therapy

Secondary Outcomes (4)

• Overall Survival (OS)

  Assessed after 2 cycles of treatment, 2 months after completion of therapy and then yearly up to 5 years

• Progression-free Survival (PFS)

  Assessed after 2 cycles of treatment, 2 months after completion of therapy and then yearly up to 5 years

• Time to Response

  Assessed after 2 cycles of treatment, 2 months after completion of therapy and then yearly up to 5 years

• Duration of Response

  Assessed after 2 cycles of treatment, 2 months after completion of therapy and then yearly up to 5 years

Study Arms (2)

Arm A (standard dose)

ACTIVE COMPARATOR

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 375 mg/m\^2/week intravenously (IV) on days 8, 15, 22, and 29 in cycle 1 (33-day cycle). In cycle 2 and subsequent cycles (28-day cycle), 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 cycles. Alemtuzumab dose for cycle 1 week 1 requires a 'dose ramp' (3 mg day 1, 10 mg day2, and 30 mg day 3 of cycle 1) and then is 30 mg 3 times a week.

Biological: alemtuzumab; Biological: rituximab

Arm B (low dose)

EXPERIMENTAL

Patients receive alemtuzumab SC on days 1-3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27, 29, and 31 and low-dose rituximab at 20 mg/m\^2 IV on days 6, 8, 10, 13, 15, 17, 20, 22, 24, 27, 29, and 31 in cycle 1 (33-day cycle). In cycle 2 and subsequent cycles (28-day cycle), patients receive alemtuzumab SC and low-dose rituximab IV on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26. Treatment repeats every 28 days for up to 3 cycles. Alemtuzumab dose for cycle 1 week 1 requires a 'dose ramp' (3 mg day 1, 10 mg day2, and 30 mg day 3 of cycle 1) and then is 30 mg 3 times a week.

Biological: alemtuzumab; Biological: rituximab

Interventions

alemtuzumab BIOLOGICAL

Given IV

Arm A (standard dose); Arm B (low dose)

rituximab BIOLOGICAL

Given IV

Arm A (standard dose); Arm B (low dose)

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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 9small lymphocytic lymphoma \[SLL\] variant)
• CD5+
• CD23+
• Dim surface light chain expression
• Dim surface CD20 expression
• FISH analysis is negative for immunoglobulin heavy chain/cyclin D1 gene (IGH/CCND1) and/or immunostaining is negative for cyclin D1 expression (to exclude mantle cell lymphoma)
• 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

You may not qualify if:

• Prior treatment for CLL
• Massive splenomegaly \> 6 cm below left costal margin, at rest, on clinical examination
• Lymphadenopathy \> 5 cm in any diameter
• New York Heart Association class III or IV heart disease
• Recent myocardial infarction (within the past month)
• Uncontrolled infection
• Infection with the human immunodeficiency virus (HIV/AIDS)
• Serological evidence of active hepatitis B infection (HBsAg or HBeAg positive)
• Positive hepatitis C serology
• Evidence of active autoimmune hemolytic anemia, immune thrombocytopenia, or pure red blood cell aplasia
• 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
• Major surgery within 4 weeks prior to pre-registration
• Concomitant use of continuous systemic corticosteroids
• Prior corticosteroids are allowed but not at time of pre-registration to the study

Sponsors & Collaborators

• ECOG-ACRIN Cancer Research Group: lead
• National Cancer Institute (NCI): collaborator

Study Sites (102)

Mayo Clinic Scottsdale

Scottsdale, Arizona, 85259-5499, United States

Location

Michael and Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital

Fort Lauderdale, Florida, 33308, United States

Location

Ella Milbank Foshay Cancer Center at Jupiter Medical Center

Jupiter, Florida, 33458, United States

Location

CCOP - Mount Sinai Medical Center

Miami Beach, Florida, 33140, United States

Location

Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/Candler

Savannah, Georgia, 31405, United States

Location

Rush-Copley Cancer Care Center

Aurora, Illinois, 60504, United States

Location

Illinois CancerCare - Bloomington

Bloomington, Illinois, 61701, United States

Location

St. Joseph Medical Center

Bloomington, Illinois, 61701, United States

Location

Graham Hospital

Canton, Illinois, 61520, United States

Location

Illinois CancerCare - Canton

Canton, Illinois, 61520, United States

Location

Illinois CancerCare - Carthage

Carthage, Illinois, 62321, United States

Location

Memorial Hospital

Carthage, Illinois, 62321, United States

Location

University of Chicago Cancer Research Center

Chicago, Illinois, 60637-1470, United States

Location

Eureka Community Hospital

Eureka, Illinois, 61530, United States

Location

Illinois CancerCare - Eureka

Eureka, Illinois, 61530, United States

Location

Galesburg Clinic, PC

Galesburg, Illinois, 61401, United States

Location

Illinois CancerCare - Havana

Havana, Illinois, 62644, United States

Location

Illinois CancerCare - Kewanee Clinic

Kewanee, Illinois, 61443, United States

Location

Illinois CancerCare - Macomb

Macomb, Illinois, 61455, United States

Location

McDonough District Hospital

Macomb, Illinois, 61455, United States

Location

Illinois CancerCare - Monmouth

Monmouth, Illinois, 61462, United States

Location

OSF Holy Family Medical Center

Monmouth, Illinois, 61462, United States

Location

BroMenn Regional Medical Center

Normal, Illinois, 61761, United States

Location

Community Cancer Center

Normal, Illinois, 61761, United States

Location

Illinois CancerCare - Community Cancer Center

Normal, Illinois, 61761, United States

Location

Community Hospital of Ottawa

Ottawa, Illinois, 61350, United States

Location

Oncology Hematology Associates of Central Illinois, PC - Ottawa

Ottawa, Illinois, 61350, United States

Location

Cancer Treatment Center at Pekin Hospital

Pekin, Illinois, 61554, United States

Location

Illinois CancerCare - Pekin

Pekin, Illinois, 61603, United States

Location

Proctor Hospital

Peoria, Illinois, 61614, United States

Location

CCOP - Illinois Oncology Research Association

Peoria, Illinois, 61615, United States

Location

Oncology Hematology Associates of Central Illinois, PC - Peoria

Peoria, Illinois, 61615, United States

Location

Methodist Medical Center of Illinois

Peoria, Illinois, 61636, United States

Location

OSF St. Francis Medical Center

Peoria, Illinois, 61637, United States

Location

Illinois CancerCare - Peru

Peru, Illinois, 61354, United States

Location

Illinois Valley Community Hospital

Peru, Illinois, 61354, United States

Location

Illinois CancerCare - Princeton

Princeton, Illinois, 61356, United States

Location

Swedish-American Regional Cancer Center

Rockford, Illinois, 61104-2315, United States

Location

Illinois CancerCare - Spring Valley

Spring Valley, Illinois, 61362, United States

Location

CCOP - Carle Cancer Center

Urbana, Illinois, 61801, United States

Location

St. Francis Hospital and Health Centers - Beech Grove Campus

Beech Grove, Indiana, 46107, United States

Location

Reid Hospital & Health Care Services

Richmond, Indiana, 47374, United States

Location

McFarland Clinic, PC

Ames, Iowa, 50010, United States

Location

Cedar Rapids Oncology Associates

Cedar Rapids, Iowa, 52403, United States

Location

Mercy Regional Cancer Center at Mercy Medical Center

Cedar Rapids, Iowa, 52403, United States

Location

Mercy Cancer Center at Mercy Medical Center - North Iowa

Mason City, Iowa, 50401, United States

Location

Siouxland Hematology-Oncology Associates, LLP

Sioux City, Iowa, 51101, United States

Location

Mercy Medical Center - Sioux City

Sioux City, Iowa, 51102, United States

Location

St. Luke's Regional Medical Center

Sioux City, Iowa, 51104, United States

Location

Tulane Cancer Center Office of Clinical Research

Alexandria, Louisiana, 71315-3198, United States

Location

Hematology-Oncology Clinic

Baton Rouge, Louisiana, 70809, United States

Location

Feist-Weiller Cancer Center at Louisiana State University Health Sciences

Shreveport, Louisiana, 71130-3932, United States

Location

Borgess Medical Center

Kalamazoo, Michigan, 49001, United States

Location

West Michigan Cancer Center

Kalamazoo, Michigan, 49007-3731, United States

Location

Bronson Methodist Hospital

Kalamazoo, Michigan, 49007, United States

Location

Upper Michigan Cancer Center at Marquette General Hospital

Marquette, Michigan, 49855, United States

Location

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905, United States

Location

Central Care Cancer Center at Carrie J. Babb Cancer Center

Bolivar, Missouri, 65613, United States

Location

Skaggs Cancer Center at Skaggs Regional Medical Center

Branson, Missouri, 65616, United States

Location

Southeast Cancer Center

Cape Girardeau, Missouri, 63703, United States

Location

Goldschmidt Cancer Center

Jefferson City, Missouri, 65109, United States

Location

Mercy Clinic Cancer and Hematology - Rolla

Rolla, Missouri, 65401, United States

Location

Phelps County Regional Medical Center

Rolla, Missouri, 65401, United States

Location

CCOP - Cancer Research for the Ozarks

Springfield, Missouri, 65802, United States

Location

St. John's Regional Health Center

Springfield, Missouri, 65804, United States

Location

Hulston Cancer Center at Cox Medical Center South

Springfield, Missouri, 65807, United States

Location

Missouri Baptist Cancer Center

St Louis, Missouri, 63131, United States

Location

CCOP - Nevada Cancer Research Foundation

Las Vegas, Nevada, 89106, United States

Location

Randolph Hospital

Asheboro, North Carolina, 27203-5400, United States

Location

Wayne Memorial Hospital, Incorporated

Goldsboro, North Carolina, 27534, United States

Location

Moses Cone Regional Cancer Center at Wesley Long Community Hospital

Greensboro, North Carolina, 27403-1198, United States

Location

Pardee Memorial Hospital

Hendersonville, North Carolina, 28791, United States

Location

Kinston Medical Specialists

Kinston, North Carolina, 28501, United States

Location

Annie Penn Cancer Center

Reidsville, North Carolina, 27320, United States

Location

Iredell Memorial Hospital

Statesville, North Carolina, 28677, United States

Location

Medcenter One Hospital Cancer Care Center

Bismarck, North Dakota, 58501, United States

Location

Mid Dakota Clinic, PC

Bismarck, North Dakota, 58501, United States

Location

St. Alexius Medical Center Cancer Center

Bismarck, North Dakota, 58502, United States

Location

Aultman Cancer Center at Aultman Hospital

Canton, Ohio, 44710-1799, United States

Location

Grandview Hospital

Dayton, Ohio, 45405, United States

Location

Good Samaritan Hospital

Dayton, Ohio, 45406, United States

Location

David L. Rike Cancer Center at Miami Valley Hospital

Dayton, Ohio, 45409, United States

Location

Samaritan North Cancer Care Center

Dayton, Ohio, 45415, United States

Location

CCOP - Dayton

Dayton, Ohio, 45420, United States

Location

Blanchard Valley Medical Associates

Findlay, Ohio, 45840, United States

Location

Middletown Regional Hospital

Franklin, Ohio, 45005-1066, United States

Location

Wayne Hospital

Greenville, Ohio, 45331, United States

Location

Charles F. Kettering Memorial Hospital

Kettering, Ohio, 45429, United States

Location

St. Rita's Medical Center

Lima, Ohio, 45801, United States

Location

UVMC Cancer Care Center at Upper Valley Medical Center

Troy, Ohio, 45373-1300, United States

Location

Ruth G. McMillan Cancer Center at Greene Memorial Hospital

Xenia, Ohio, 45385, United States

Location

Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033-0850, United States

Location

Lewistown Hospital

Lewistown, Pennsylvania, 17044, United States

Location

Mercy Hospital Cancer Center - Scranton

Scranton, Pennsylvania, 18501, United States

Location

Hematology and Oncology Associates of Northeastern Pennsylvania

Scranton, Pennsylvania, 18510, United States

Location

Mount Nittany Medical Center

State College, Pennsylvania, 16803, United States

Location

U.T. Medical Center Cancer Institute

Knoxville, Tennessee, 37920-6999, United States

Location

Danville Regional Medical Center

Danville, Virginia, 24541, United States

Location

UW Cancer Center Johnson Creek

Johnson Creek, Wisconsin, 53038, United States

Location

Gundersen Lutheran Center for Cancer and Blood

La Crosse, Wisconsin, 54601, United States

Location

University of Wisconsin Paul P. Carbone Comprehensive Cancer Center

Madison, Wisconsin, 53792-6164, United States

Location

Riverview UW Cancer Center at Riverview Hospital

Wisconsin Rapids, Wisconsin, 54494, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Alemtuzumab; Rituximab

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Antibodies, Monoclonal, Murine-Derived

Results Point of Contact

• Title: Study Statistician
• Organization: ECOG-ACRIN Statistical Office

617-632-3012

Study Officials

• Clive S. Zent, MD

  University of Rochester

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 13, 2009
• First Posted: November 16, 2009
• Study Start: April 27, 2011
• Primary Completion: April 14, 2015
• Study Completion: April 14, 2015
• Last Updated: June 28, 2023
• Results First Posted: January 28, 2016

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will share

Locations

US (102)