Fludarabine Followed by Alemtuzumab in Treating Patients With Chronic Lymphocytic Leukemia

NCT ID: NCT00004857

Last Updated: 2016-07-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 86 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2000-01-31
• Study Completion Date: 2010-02-28

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies such as alemtuzumab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells.

PURPOSE: Phase II trial to study the effectiveness of fludarabine followed by alemtuzumab in treating patients who have chronic lymphocytic leukemia.

Detailed Description

OBJECTIVES: I. Determine the overall response rate of previously untreated patients with stage I, II, III, or IV B-cell chronic lymphocytic leukemia when treated with fludarabine induction followed by alemtuzumab consolidation. II. Determine the infectious toxic effects and feasibility of this regimen in this patient population. III. Determine the treatment-related toxic effects, including infection and injection site reactions, of subcutaneous vs intravenous alemtuzumab in patients treated with this regimen. IV. Determine the progression-free and overall survival of patients treated with this regimen. V. Determine the immunologic effects of this regimen in these patients.

OUTLINE: Patients receive fludarabine IV over 30 minutes 5 days a week. Treatment repeats every 28 days for 4 courses in the absence of disease progression. Patients undergo clinical staging after completion of course 4 of fludarabine followed by 2 months of observation. Patients with stable or responding disease receive alemtuzumab subcutaneously 3 days a week for 6 weeks. Patients undergo clinical staging again after completion of 6 weeks of alemtuzumab followed by 2 more months of observation. Patients are followed every 3 months for 1 year and then every 6 months for 8 years.

Conditions

Leukemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Fludarabine + Campath-1H

Standard of care induction with fludarabine followed by consolidation antibody therapy

Group Type: EXPERIMENTAL

alemtuzumab

Intervention Type: BIOLOGICAL

30 mg subQ injection tiw for 6 weeks

fludarabine phosphate

Intervention Type: DRUG

25mg/sq m/day IV infusion x 5 days Wks 1, 5, 9, and 13

Interventions

alemtuzumab

30 mg subQ injection tiw for 6 weeks

Intervention Type: BIOLOGICAL

fludarabine phosphate

25mg/sq m/day IV infusion x 5 days Wks 1, 5, 9, and 13

Intervention Type: DRUG

Other Intervention Names

campath-1H

Eligibility Criteria

Inclusion Criteria

1. Specific Diagnosis of B-Cell CLL

1.1 An absolute lymphocytosis of > 5,000/µl

1.1.1 Morphologically, the lymphocytes must appear mature with < 55% prolymphocytes.

1.1.2 Bone marrow examination must include at least a unilateral aspirate and biopsy. The aspirate smear must show > 30% of all nucleated cells to be lymphoid or the bone marrow core biopsy must show lymphoid infiltrates compatible with marrow involvement by CLL. The overall cellularity must be normocellular or hypercellular.

1.1.3 Local institution lymphocyte phenotype must reveal a predominant B-cell monoclonal population sharing a B-cell marker (CD19, CD20, CD23, CD24) with the CD5 antigen, in the absence of other pan-T-cell markers. Additionally, the B-cells must be monoclonal with regard to expression of either κ or λ and have surface immunoglobulin expression of low density. Patients with bright surface immunoglobulin levels must have CD23 co-expression.

1.2 Staging

1.2.1 Patients must be in the intermediate- or high-risk categories of the modified three-stage Rai staging system (i.e., stages I, II, III, or IV) per the protocol.

1.2.2 Patients in the intermediate-risk group must have evidence of active disease as demonstrated by at least one of the following criteria:

• Massive or progressive splenomegaly and/or lymphadenopathy
• Presence of weight loss > 10% over the preceding 6 month period;
• Grade 2 or 3 fatigue
• Fevers > 100.5°C or night sweats for greater than 2 weeks without evidence of infection
• Progressive lymphocytosis with an increase of > 50% over a 2 month period or an anticipated doubling time of less than 6 months.

2. Prior Treatment: No prior therapy for CLL including corticosteroids for autoimmune complications that have developed since the initial diagnosis of CLL.

3. No medical condition requiring chronic use of oral corticosteroids.

4. Age ≥18 years.

5. Performance Status 0 - 2.

6. No HIV disease. Due to alterations in host immunity, patients with HIV may not be enrolled.

7. Non-pregnant and non-nursing. Due to the unknown teratogenic potential of Campath-1H, pregnant or nursing women may not be enrolled. Women and men of reproductive potential should agree to use an effective means of birth control.

8. Initial Required Laboratory Values:

Creatinine <1.5 x upper limit of institutional normal value Coomb's Testing NEGATIVE

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Alliance for Clinical Trials in Oncology

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kanti R. Rai, MD

Role: STUDY_CHAIR

Long Island Jewish Medical Center

Locations

Veterans Affairs Medical Center - Birmingham

Birmingham, Alabama, United States

University of California San Diego Cancer Center

La Jolla, California, United States

Veterans Affairs Medical Center - San Francisco

San Francisco, California, United States

UCSF Cancer Center and Cancer Research Institute

San Francisco, California, United States

CCOP - Christiana Care Health Services

Wilmington, Delaware, United States

Lombardi Cancer Center

Washington D.C., District of Columbia, United States

Walter Reed Army Medical Center

Washington D.C., District of Columbia, United States

CCOP - Mount Sinai Medical Center

Miami Beach, Florida, United States

University of Illinois at Chicago Health Sciences Center

Chicago, Illinois, United States

Veterans Affairs Medical Center - Chicago (Westside Hospital)

Chicago, Illinois, United States

University of Chicago Cancer Research Center

Chicago, Illinois, United States

Holden Comprehensive Cancer Center at The University of Iowa

Iowa City, Iowa, United States

Veterans Affairs Medical Center - Togus

Togus, Maine, United States

Marlene & Stewart Greenebaum Cancer Center, University of Maryland

Baltimore, Maryland, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

University of Massachusetts Memorial Medical Center

Worcester, Massachusetts, United States

Veterans Affairs Medical Center - Minneapolis

Minneapolis, Minnesota, United States

University of Minnesota Cancer Center

Minneapolis, Minnesota, United States

Veterans Affairs Medical Center - Columbia (Truman Memorial)

Columbia, Missouri, United States

Ellis Fischel Cancer Center - Columbia

Columbia, Missouri, United States

Barnes-Jewish Hospital

St Louis, Missouri, United States

University of Nebraska Medical Center

Omaha, Nebraska, United States

CCOP - Southern Nevada Cancer Research Foundation

Las Vegas, Nevada, United States

Norris Cotton Cancer Center

Lebanon, New Hampshire, United States

Veterans Affairs Medical Center - Buffalo

Buffalo, New York, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

CCOP - North Shore University Hospital

Manhasset, New York, United States

North Shore University Hospital

Manhasset, New York, United States

Long Island Jewish Medical Center

New Hyde Park, New York, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

New York Presbyterian Hospital - Cornell Campus

New York, New York, United States

Mount Sinai Medical Center, NY

New York, New York, United States

State University of New York - Upstate Medical University

Syracuse, New York, United States

Veterans Affairs Medical Center - Syracuse

Syracuse, New York, United States

CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.

Syracuse, New York, United States

Lineberger Comprehensive Cancer Center, UNC

Chapel Hill, North Carolina, United States

Veterans Affairs Medical Center - Durham

Durham, North Carolina, United States

Duke Comprehensive Cancer Center

Durham, North Carolina, United States

CCOP - Southeast Cancer Control Consortium

Winston-Salem, North Carolina, United States

Comprehensive Cancer Center at Wake Forest University

Winston-Salem, North Carolina, United States

Arthur G. James Cancer Hospital - Ohio State University

Columbus, Ohio, United States

Rhode Island Hospital

Providence, Rhode Island, United States

Medical University of South Carolina

Charleston, South Carolina, United States

University of Tennessee, Memphis Cancer Center

Memphis, Tennessee, United States

Veterans Affairs Medical Center - Memphis

Memphis, Tennessee, United States

CCOP - Southwestern Vermont Regional Cancer Center

Bennington, Vermont, United States

Vermont Cancer Center

Burlington, Vermont, United States

Veterans Affairs Medical Center - White River Junction

White River Junction, Vermont, United States

Veterans Affairs Medical Center - Richmond

Richmond, Virginia, United States

MBCCOP - Massey Cancer Center

Richmond, Virginia, United States

Countries

United States

References

Morrison VA, Peterson BL, Rai KR, et al.: Alemtuzumab increases serious infections in patients with previously untreated chronic lymphocytic leukemia (CLL) receiving fludarabine-based therapy: a comparative analysis of 3 Cancer and Leukemia Group B studies (CALGB 9011, 9712, 19901). [Abstract] Blood 110 (11): A-756, 2007.

Reference Type: BACKGROUND

Rai KR, Freter CE, Mercier RJ, Cooper MR, Mitchell BS, Stadtmauer EA, Santabarbara P, Wacker B, Brettman L. Alemtuzumab in previously treated chronic lymphocytic leukemia patients who also had received fludarabine. J Clin Oncol. 2002 Sep 15;20(18):3891-7. doi: 10.1200/JCO.2002.06.119.

Reference Type: BACKGROUND

PMID: 12228210 (View on PubMed)

Byrd JC, Peterson BL, Rai KR, Hurd D, Hohl R, Perry MC, Gockerman J, Nattam S, Larson RA. Fludarabine followed by alemtuzumab consolidation for previously untreated chronic lymphocytic leukemia: final report of Cancer and Leukemia Group B study 19901. Leuk Lymphoma. 2009 Oct;50(10):1589-96. doi: 10.1080/10428190903150839.

Reference Type: RESULT

PMID: 19863336 (View on PubMed)

Rai KR, Byrd JC, Peterson B: Subcutaneous alemtuzumab following fludarabine for previously untreated patients with chronic lymphocytic leukemia (CLL): CALGB study 19901. [Abstract] Blood 102 (11 Pt 1): A-2506, 2003.

Reference Type: RESULT

Rai KR, Byrd JC, Peterson BL, et al.: A phase II trial of fludarabine followed by alemtuzumab (Campath-1H) in previously untreated chronic lymphocytic leukemia (CLL) patients with active disease: Cancer and Leukemia Group B (CALGB) study 19901. [Abstract] Blood 100 (11 Pt 1): A-772, 2002.

Reference Type: RESULT

Jones JA, Ruppert AS, Zhao W, Lin TS, Rai K, Peterson B, Larson RA, Marcucci G, Heerema NA, Byrd JC. Patients with chronic lymphocytic leukemia with high-risk genomic features have inferior outcome on successive Cancer and Leukemia Group B trials with alemtuzumab consolidation: subgroup analysis from CALGB 19901 and CALGB 10101. Leuk Lymphoma. 2013 Dec;54(12):2654-9. doi: 10.3109/10428194.2013.788179. Epub 2013 May 9.

Reference Type: DERIVED

PMID: 23547837 (View on PubMed)

Other Identifiers

U10CA031946

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CDR0000067506

Identifier Type: REGISTRY

Identifier Source: secondary_id

CALGB-19901

Identifier Type: -

Identifier Source: org_study_id