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.
調査の概要
詳細な説明
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.
研究の種類
入学 (実際)
段階
- フェーズ2
連絡先と場所
研究場所
-
-
Alabama
-
Birmingham、Alabama、アメリカ、35233-1996
- Veterans Affairs Medical Center - Birmingham
-
-
California
-
La Jolla、California、アメリカ、92093-0658
- University of California San Diego Cancer Center
-
San Francisco、California、アメリカ、94121
- Veterans Affairs Medical Center - San Francisco
-
San Francisco、California、アメリカ、94143-0128
- UCSF Cancer Center and Cancer Research Institute
-
-
Delaware
-
Wilmington、Delaware、アメリカ、19899
- CCOP - Christiana Care Health Services
-
-
District of Columbia
-
Washington、District of Columbia、アメリカ、20307-5000
- Walter Reed Army Medical Center
-
Washington、District of Columbia、アメリカ、20007
- Lombardi Cancer Center
-
-
Florida
-
Miami Beach、Florida、アメリカ、33140
- CCOP - Mount Sinai Medical Center
-
-
Illinois
-
Chicago、Illinois、アメリカ、60612
- Veterans Affairs Medical Center - Chicago (Westside Hospital)
-
Chicago、Illinois、アメリカ、60637-1470
- University of Chicago Cancer Research Center
-
Chicago、Illinois、アメリカ、60612
- University of Illinois at Chicago Health Sciences Center
-
-
Iowa
-
Iowa City、Iowa、アメリカ、52242-1009
- Holden Comprehensive Cancer Center at the University of Iowa
-
-
Maine
-
Togus、Maine、アメリカ、04330
- Veterans Affairs Medical Center - Togus
-
-
Maryland
-
Baltimore、Maryland、アメリカ、21201
- Marlene & Stewart Greenebaum Cancer Center, University of Maryland
-
-
Massachusetts
-
Boston、Massachusetts、アメリカ、02115
- Dana-Farber Cancer Institute
-
Worcester、Massachusetts、アメリカ、01655
- University of Massachusetts Memorial Medical Center
-
-
Minnesota
-
Minneapolis、Minnesota、アメリカ、55417
- Veterans Affairs Medical Center - Minneapolis
-
Minneapolis、Minnesota、アメリカ、55455
- University of Minnesota Cancer Center
-
-
Missouri
-
Columbia、Missouri、アメリカ、65201
- Veterans Affairs Medical Center - Columbia (Truman Memorial)
-
Columbia、Missouri、アメリカ、65203
- Ellis Fischel Cancer Center - Columbia
-
Saint Louis、Missouri、アメリカ、63110
- Barnes-Jewish Hospital
-
-
Nebraska
-
Omaha、Nebraska、アメリカ、68198-3330
- University of Nebraska Medical Center
-
-
Nevada
-
Las Vegas、Nevada、アメリカ、89106
- CCOP - Southern Nevada Cancer Research Foundation
-
-
New Hampshire
-
Lebanon、New Hampshire、アメリカ、03756-0002
- Norris Cotton Cancer Center
-
-
New York
-
Buffalo、New York、アメリカ、14263-0001
- Roswell Park Cancer Institute
-
Buffalo、New York、アメリカ、14215
- Veterans Affairs Medical Center - Buffalo
-
Manhasset、New York、アメリカ、11030
- CCOP - North Shore University Hospital
-
Manhasset、New York、アメリカ、11030
- North Shore University Hospital
-
New Hyde Park、New York、アメリカ、11040
- Long Island Jewish Medical Center
-
New York、New York、アメリカ、10021
- Memorial Sloan-Kettering Cancer Center
-
New York、New York、アメリカ、10021
- New York Presbyterian Hospital - Cornell Campus
-
New York、New York、アメリカ、10029
- Mount Sinai Medical Center, NY
-
Syracuse、New York、アメリカ、13210
- State University of New York - Upstate Medical University
-
Syracuse、New York、アメリカ、13210
- Veterans Affairs Medical Center - Syracuse
-
Syracuse、New York、アメリカ、13217
- CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.
-
-
North Carolina
-
Chapel Hill、North Carolina、アメリカ、27599-7295
- Lineberger Comprehensive Cancer Center, UNC
-
Durham、North Carolina、アメリカ、27705
- Veterans Affairs Medical Center - Durham
-
Durham、North Carolina、アメリカ、27710
- Duke Comprehensive Cancer Center
-
Winston-Salem、North Carolina、アメリカ、27104-4241
- CCOP - Southeast Cancer Control Consortium
-
Winston-Salem、North Carolina、アメリカ、27157-1082
- Comprehensive Cancer Center at Wake Forest University
-
-
Ohio
-
Columbus、Ohio、アメリカ、43210-1240
- Arthur G. James Cancer Hospital - Ohio State University
-
-
Rhode Island
-
Providence、Rhode Island、アメリカ、02903
- Rhode Island Hospital
-
-
South Carolina
-
Charleston、South Carolina、アメリカ、29425-0721
- Medical University of South Carolina
-
-
Tennessee
-
Memphis、Tennessee、アメリカ、38103
- University of Tennessee, Memphis Cancer Center
-
Memphis、Tennessee、アメリカ、38104
- Veterans Affairs Medical Center - Memphis
-
-
Vermont
-
Bennington、Vermont、アメリカ、05201
- CCOP - Southwestern Vermont Regional Cancer Center
-
Burlington、Vermont、アメリカ、05401-3498
- Vermont Cancer Center
-
White River Junction、Vermont、アメリカ、05009
- Veterans Affairs Medical Center - White River Junction
-
-
Virginia
-
Richmond、Virginia、アメリカ、23298-0037
- MBCCOP - Massey Cancer Center
-
Richmond、Virginia、アメリカ、23249
- Veterans Affairs Medical Center - Richmond
-
-
参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：非ランダム化
- 介入モデル：単一グループの割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：Fludarabine + Campath-1H
Standard of care induction with fludarabine followed by consolidation antibody therapy
|
30 mg subQ injection tiw for 6 weeks
他の名前：
25mg/sq m/day IV infusion x 5 days Wks 1, 5, 9, and 13
|
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
時間枠 |
|---|---|
|
Response
時間枠：2 months post consolidation
|
2 months post consolidation
|
二次結果の測定
結果測定 |
時間枠 |
|---|---|
|
Toxicity
時間枠：2 months post consolidation
|
2 months post consolidation
|
協力者と研究者
捜査官
- スタディチェア：Kanti R. Rai, MD、Long Island Jewish Medical Center
出版物と役立つリンク
一般刊行物
- 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.
研究記録日
主要日程の研究
研究開始
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (見積もり)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- CALGB-19901
- U10CA031946 (米国 NIH グラント/契約)
- CDR0000067506 (レジストリ識別子：NCI Physician Data Query)
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。
alemtuzumabの臨床試験
-
National Institute of Allergy and Infectious Diseases...PPD; Rho Federal Systems Division, Inc.; Immune Tolerance Network (ITN); Blood and Marrow Transplant...募集