- ICH GCP
- US Clinical Trials Registry
- Klinisk utprøving NCT00004857
Fludarabine Followed by Alemtuzumab in Treating Patients With Chronic Lymphocytic Leukemia
A Phase II Study of Fludarabine Induction Followed by CAMPATH-1H Consolidation in Untreated Patients With B-Cell Chronic Lymphocytic Leukemia
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.
Studieoversikt
Status
Forhold
Intervensjon / Behandling
Detaljert beskrivelse
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.
Studietype
Registrering (Faktiske)
Fase
- Fase 2
Kontakter og plasseringer
Studiesteder
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Alabama
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Birmingham, Alabama, Forente stater, 35233-1996
- Veterans Affairs Medical Center - Birmingham
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California
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La Jolla, California, Forente stater, 92093-0658
- University of California San Diego Cancer Center
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San Francisco, California, Forente stater, 94121
- Veterans Affairs Medical Center - San Francisco
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San Francisco, California, Forente stater, 94143-0128
- UCSF Cancer Center and Cancer Research Institute
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Delaware
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Wilmington, Delaware, Forente stater, 19899
- CCOP - Christiana Care Health Services
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District of Columbia
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Washington, District of Columbia, Forente stater, 20307-5000
- Walter Reed Army Medical Center
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Washington, District of Columbia, Forente stater, 20007
- Lombardi Cancer Center
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Florida
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Miami Beach, Florida, Forente stater, 33140
- CCOP - Mount Sinai Medical Center
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Illinois
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Chicago, Illinois, Forente stater, 60612
- Veterans Affairs Medical Center - Chicago (Westside Hospital)
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Chicago, Illinois, Forente stater, 60637-1470
- University of Chicago Cancer Research Center
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Chicago, Illinois, Forente stater, 60612
- University of Illinois at Chicago Health Sciences Center
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Iowa
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Iowa City, Iowa, Forente stater, 52242-1009
- Holden Comprehensive Cancer Center at the University of Iowa
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Maine
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Togus, Maine, Forente stater, 04330
- Veterans Affairs Medical Center - Togus
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Maryland
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Baltimore, Maryland, Forente stater, 21201
- Marlene & Stewart Greenebaum Cancer Center, University of Maryland
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Massachusetts
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Boston, Massachusetts, Forente stater, 02115
- Dana-Farber Cancer Institute
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Worcester, Massachusetts, Forente stater, 01655
- University of Massachusetts Memorial Medical Center
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Minnesota
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Minneapolis, Minnesota, Forente stater, 55417
- Veterans Affairs Medical Center - Minneapolis
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Minneapolis, Minnesota, Forente stater, 55455
- University of Minnesota Cancer Center
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Missouri
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Columbia, Missouri, Forente stater, 65201
- Veterans Affairs Medical Center - Columbia (Truman Memorial)
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Columbia, Missouri, Forente stater, 65203
- Ellis Fischel Cancer Center - Columbia
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Saint Louis, Missouri, Forente stater, 63110
- Barnes-Jewish Hospital
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Nebraska
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Omaha, Nebraska, Forente stater, 68198-3330
- University of Nebraska Medical Center
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Nevada
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Las Vegas, Nevada, Forente stater, 89106
- CCOP - Southern Nevada Cancer Research Foundation
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New Hampshire
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Lebanon, New Hampshire, Forente stater, 03756-0002
- Norris Cotton Cancer Center
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New York
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Buffalo, New York, Forente stater, 14263-0001
- Roswell Park Cancer Institute
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Buffalo, New York, Forente stater, 14215
- Veterans Affairs Medical Center - Buffalo
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Manhasset, New York, Forente stater, 11030
- CCOP - North Shore University Hospital
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Manhasset, New York, Forente stater, 11030
- North Shore University Hospital
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New Hyde Park, New York, Forente stater, 11040
- Long Island Jewish Medical Center
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New York, New York, Forente stater, 10021
- Memorial Sloan-Kettering Cancer Center
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New York, New York, Forente stater, 10021
- New York Presbyterian Hospital - Cornell Campus
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New York, New York, Forente stater, 10029
- Mount Sinai Medical Center, NY
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Syracuse, New York, Forente stater, 13210
- State University of New York - Upstate Medical University
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Syracuse, New York, Forente stater, 13210
- Veterans Affairs Medical Center - Syracuse
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Syracuse, New York, Forente stater, 13217
- CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.
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North Carolina
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Chapel Hill, North Carolina, Forente stater, 27599-7295
- Lineberger Comprehensive Cancer Center, UNC
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Durham, North Carolina, Forente stater, 27705
- Veterans Affairs Medical Center - Durham
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Durham, North Carolina, Forente stater, 27710
- Duke Comprehensive Cancer Center
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Winston-Salem, North Carolina, Forente stater, 27104-4241
- CCOP - Southeast Cancer Control Consortium
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Winston-Salem, North Carolina, Forente stater, 27157-1082
- Comprehensive Cancer Center at Wake Forest University
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Ohio
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Columbus, Ohio, Forente stater, 43210-1240
- Arthur G. James Cancer Hospital - Ohio State University
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Rhode Island
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Providence, Rhode Island, Forente stater, 02903
- Rhode Island Hospital
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South Carolina
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Charleston, South Carolina, Forente stater, 29425-0721
- Medical University of South Carolina
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Tennessee
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Memphis, Tennessee, Forente stater, 38103
- University of Tennessee, Memphis Cancer Center
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Memphis, Tennessee, Forente stater, 38104
- Veterans Affairs Medical Center - Memphis
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Vermont
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Bennington, Vermont, Forente stater, 05201
- CCOP - Southwestern Vermont Regional Cancer Center
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Burlington, Vermont, Forente stater, 05401-3498
- Vermont Cancer Center
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White River Junction, Vermont, Forente stater, 05009
- Veterans Affairs Medical Center - White River Junction
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Virginia
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Richmond, Virginia, Forente stater, 23298-0037
- MBCCOP - Massey Cancer Center
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Richmond, Virginia, Forente stater, 23249
- Veterans Affairs Medical Center - Richmond
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Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
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.
- Prior Treatment: No prior therapy for CLL including corticosteroids for autoimmune complications that have developed since the initial diagnosis of CLL.
- No medical condition requiring chronic use of oral corticosteroids.
- Age ≥18 years.
- Performance Status 0 - 2.
- No HIV disease. Due to alterations in host immunity, patients with HIV may not be enrolled.
- 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.
- Initial Required Laboratory Values:
Creatinine <1.5 x upper limit of institutional normal value Coomb's Testing NEGATIVE
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Ikke-randomisert
- Intervensjonsmodell: Enkeltgruppeoppdrag
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
|
Eksperimentell: Fludarabine + Campath-1H
Standard of care induction with fludarabine followed by consolidation antibody therapy
|
30 mg subQ injection tiw for 6 weeks
Andre navn:
25mg/sq m/day IV infusion x 5 days Wks 1, 5, 9, and 13
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tidsramme |
|---|---|
|
Response
Tidsramme: 2 months post consolidation
|
2 months post consolidation
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Sekundære resultatmål
Resultatmål |
Tidsramme |
|---|---|
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Toxicity
Tidsramme: 2 months post consolidation
|
2 months post consolidation
|
Samarbeidspartnere og etterforskere
Samarbeidspartnere
Etterforskere
- Studiestol: Kanti R. Rai, MD, Long Island Jewish Medical Center
Publikasjoner og nyttige lenker
Generelle publikasjoner
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Studierekorddatoer
Studer hoveddatoer
Studiestart
Primær fullføring (Faktiske)
Studiet fullført (Faktiske)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Anslag)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Anslag)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
- Sykdommer i immunsystemet
- Neoplasmer etter histologisk type
- Neoplasmer
- Lymfoproliferative lidelser
- Lymfesykdommer
- Immunproliferative lidelser
- Leukemi, B-celle
- Leukemi
- Leukemi, lymfatisk, kronisk, B-celle
- Leukemi, lymfoid
- Fysiologiske effekter av legemidler
- Molekylære mekanismer for farmakologisk virkning
- Antimetabolitter, antineoplastisk
- Antimetabolitter
- Antineoplastiske midler
- Immunsuppressive midler
- Immunologiske faktorer
- Antineoplastiske midler, immunologiske
- Fludarabin
- Fludarabinfosfat
- Alemtuzumab
Andre studie-ID-numre
- CALGB-19901
- U10CA031946 (U.S. NIH-stipend/kontrakt)
- CDR0000067506 (Registeridentifikator: NCI Physician Data Query)
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