Fludarabine Followed by Alemtuzumab in Treating Patients With Chronic Lymphocytic Leukemia

NCT00004857 | Completed Phase 2

• 3 other identifiers: CALGB-19901U10CA031946CDR0000067506
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 50

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.

Conditions

Leukemia

Keywords

stage I chronic lymphocytic leukemia; stage II chronic lymphocytic leukemia; stage III chronic lymphocytic leukemia; stage IV chronic lymphocytic leukemia; B-cell chronic lymphocytic leukemia

Outcome Measures

Primary Outcomes (1)

• Response

  2 months post consolidation

Secondary Outcomes (1)

• Toxicity

  2 months post consolidation

Study Arms (1)

Fludarabine + Campath-1H

EXPERIMENTAL

Standard of care induction with fludarabine followed by consolidation antibody therapy

Biological: alemtuzumab; Drug: fludarabine phosphate

Interventions

alemtuzumab BIOLOGICAL

30 mg subQ injection tiw for 6 weeks

Also known as: campath-1H

Fludarabine + Campath-1H

fludarabine phosphate DRUG

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

Fludarabine + Campath-1H

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Alliance for Clinical Trials in Oncology: lead
• National Cancer Institute (NCI): collaborator

Study Sites (50)

Veterans Affairs Medical Center - Birmingham

Birmingham, Alabama, 35233-1996, United States

Location

University of California San Diego Cancer Center

La Jolla, California, 92093-0658, United States

Location

Veterans Affairs Medical Center - San Francisco

San Francisco, California, 94121, United States

Location

UCSF Cancer Center and Cancer Research Institute

San Francisco, California, 94143-0128, United States

Location

CCOP - Christiana Care Health Services

Wilmington, Delaware, 19899, United States

Location

Lombardi Cancer Center

Washington D.C., District of Columbia, 20007, United States

Location

Walter Reed Army Medical Center

Washington D.C., District of Columbia, 20307-5000, United States

Location

CCOP - Mount Sinai Medical Center

Miami Beach, Florida, 33140, United States

Location

University of Illinois at Chicago Health Sciences Center

Chicago, Illinois, 60612, United States

Location

Veterans Affairs Medical Center - Chicago (Westside Hospital)

Chicago, Illinois, 60612, United States

Location

University of Chicago Cancer Research Center

Chicago, Illinois, 60637-1470, United States

Location

Holden Comprehensive Cancer Center at The University of Iowa

Iowa City, Iowa, 52242-1009, United States

Location

Veterans Affairs Medical Center - Togus

Togus, Maine, 04330, United States

Location

Marlene & Stewart Greenebaum Cancer Center, University of Maryland

Baltimore, Maryland, 21201, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

University of Massachusetts Memorial Medical Center

Worcester, Massachusetts, 01655, United States

Location

Veterans Affairs Medical Center - Minneapolis

Minneapolis, Minnesota, 55417, United States

Location

University of Minnesota Cancer Center

Minneapolis, Minnesota, 55455, United States

Location

Veterans Affairs Medical Center - Columbia (Truman Memorial)

Columbia, Missouri, 65201, United States

Location

Ellis Fischel Cancer Center - Columbia

Columbia, Missouri, 65203, United States

Location

Barnes-Jewish Hospital

St Louis, Missouri, 63110, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198-3330, United States

Location

CCOP - Southern Nevada Cancer Research Foundation

Las Vegas, Nevada, 89106, United States

Location

Norris Cotton Cancer Center

Lebanon, New Hampshire, 03756-0002, United States

Location

Veterans Affairs Medical Center - Buffalo

Buffalo, New York, 14215, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263-0001, United States

Location

CCOP - North Shore University Hospital

Manhasset, New York, 11030, United States

Location

North Shore University Hospital

Manhasset, New York, 11030, United States

Location

Long Island Jewish Medical Center

New Hyde Park, New York, 11040, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10021, United States

Location

New York Presbyterian Hospital - Cornell Campus

New York, New York, 10021, United States

Location

Mount Sinai Medical Center, NY

New York, New York, 10029, United States

Location

State University of New York - Upstate Medical University

Syracuse, New York, 13210, United States

Location

Veterans Affairs Medical Center - Syracuse

Syracuse, New York, 13210, United States

Location

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

Syracuse, New York, 13217, United States

Location

Lineberger Comprehensive Cancer Center, UNC

Chapel Hill, North Carolina, 27599-7295, United States

Location

Veterans Affairs Medical Center - Durham

Durham, North Carolina, 27705, United States

Location

Duke Comprehensive Cancer Center

Durham, North Carolina, 27710, United States

Location

CCOP - Southeast Cancer Control Consortium

Winston-Salem, North Carolina, 27104-4241, United States

Location

Comprehensive Cancer Center at Wake Forest University

Winston-Salem, North Carolina, 27157-1082, United States

Location

Arthur G. James Cancer Hospital - Ohio State University

Columbus, Ohio, 43210-1240, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425-0721, United States

Location

University of Tennessee, Memphis Cancer Center

Memphis, Tennessee, 38103, United States

Location

Veterans Affairs Medical Center - Memphis

Memphis, Tennessee, 38104, United States

Location

CCOP - Southwestern Vermont Regional Cancer Center

Bennington, Vermont, 05201, United States

Location

Vermont Cancer Center

Burlington, Vermont, 05401-3498, United States

Location

Veterans Affairs Medical Center - White River Junction

White River Junction, Vermont, 05009, United States

Location

Veterans Affairs Medical Center - Richmond

Richmond, Virginia, 23249, United States

Location

MBCCOP - Massey Cancer Center

Richmond, Virginia, 23298-0037, United States

Location

Related Publications (6)

• 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.

  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.

  PMID: 12228210 BACKGROUND

• 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.

  PMID: 19863336 RESULT

• 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.

  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.

  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.

  PMID: 23547837 DERIVED

MeSH Terms

Conditions

Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Alemtuzumab; fludarabine phosphate

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; 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

Study Officials

• Kanti R. Rai, MD

  Long Island Jewish Medical Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 7, 2000
• First Posted: December 11, 2003
• Study Start: January 1, 2000
• Primary Completion: March 1, 2003
• Study Completion: February 1, 2010
• Last Updated: July 6, 2016

Record last verified: 2016-07

Locations

US (50)