Denileukin Diftitox in Treating Patients With Fludarabine-Refractory B-Cell Chronic Lymphocytic Leukemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00082940
Recruitment Status : Completed
First Posted : May 19, 2004
Last Update Posted : January 19, 2017
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Wake Forest University Health Sciences

May 14, 2004
May 19, 2004
January 19, 2017
August 2002
January 2005   (Final data collection date for primary outcome measure)
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Complete list of historical versions of study NCT00082940 on Archive Site
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Denileukin Diftitox in Treating Patients With Fludarabine-Refractory B-Cell Chronic Lymphocytic Leukemia
A Phase II Study of ONTAK® (Denileukin Diftitox, DABIL-2) in Patients With Fludarabine-Refractory B-Cell Chronic Lymphocytic Leukemia

RATIONALE: Biological therapies, such as denileukin diftitox, may interfere with the growth of cancer cells and slow the growth of chronic lymphocytic leukemia.

PURPOSE: This phase II trial is studying how well denileukin diftitox works in treating patients with fludarabine-refractory B-cell chronic lymphocytic leukemia.



  • Determine the complete and partial response rate in patients with fludarabine-refractory B-cell chronic lymphocytic leukemia treated with denileukin diftitox.


  • Determine the toxicity profile of this drug in these patients.
  • Determine the response rate in patients (regardless of CD25 receptor density) treated with this drug.
  • Determine the progression-free survival and overall survival of patients treated with this drug.

OUTLINE: This is a multicenter study.

Patients receive denileukin diftitox IV over 1 hour on days 1-5. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

Patients achieving a complete response after 8 courses proceed to follow-up. Patients achieving a partial response or stable disease after 8 courses may continue treatment at the discretion of the investigator.

Patients are followed every 3 months for 1 year and then annually until relapse.

PROJECTED ACCRUAL: A total of 12-44 patients will be accrued for this study within 1 year.

Phase 2
Masking: None (Open Label)
Primary Purpose: Treatment
Biological: denileukin diftitox
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Frankel AE, Surendranathan A, Black JH, White A, Ganjoo K, Cripe LD. Phase II clinical studies of denileukin diftitox diphtheria toxin fusion protein in patients with previously treated chronic lymphocytic leukemia. Cancer. 2006 May 15;106(10):2158-64.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
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June 2005
January 2005   (Final data collection date for primary outcome measure)


  • Diagnosis of B-cell chronic lymphocytic leukemia (CLL) meeting the following criteria at any time during the course of disease (e.g., at initial diagnosis or relapse):

    • Absolute lymphocytosis > 5,000/mm^3
    • Lymphocytes must appear mature with < 55% prolymphocytes
    • More than 30% of all nucleated cells are lymphoid on bone marrow aspirate smear
    • Lymphoid infiltrates compatible with bone marrow involvement by CLL on core bone marrow biopsy
    • Predominant B-cell monoclonal population of cells share the B-cell marker (CD19) with the CD5 antigen in the absence of other pan-T-cell markers by lymphocyte immunophenotyping
  • High-risk disease OR intermediate-risk disease

    • Patients in the intermediate-risk group must have evidence of active disease as demonstrated by at least 1 of the following criteria:

      • Massive or progressive splenomegaly and/or adenopathy
      • Weight loss > 10% within the past 6 months
      • Common toxicity grade 2-4 fatigue
      • Fevers > 100.5°F OR night sweats for more 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 < 6 months
  • Failed at least 1 prior fludarabine regimen, as defined by 1 of the following criteria:

    • Refractory or intolerant to fludarabine
    • Relapsed within 6 months after completion of fludarabine
  • No CNS leukemia
  • No mantle cell lymphoma in leukemic phase



  • 18 and over

Performance status

  • Zubrod 0-2

Life expectancy

  • More than 2 months


  • Absolute neutrophil count ≥ 1,000/mm^3
  • Platelet count ≥ 50,000/mm^3
  • Hemoglobin ≥ 8 g/dL (transfusion allowed)


  • Albumin ≥ 3 g/dL
  • AST and ALT ≤ 2.5 times upper limit of normal (ULN)
  • Bilirubin ≤ 1.5 times ULN
  • No hepatitis B or C infection


  • Creatinine ≤ 1.5 mg/dL OR
  • Creatinine clearance ≥ 40 mL/min


  • LVEF ≥ 40%


  • No uncontrolled infection
  • No other concurrent serious illness
  • No HIV infection
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use two effective methods of contraception (one must be non-hormonal) during and for at least 1 month after study participation


Biologic therapy

  • Prior denileukin diftitox allowed


  • See Disease Characteristics

Endocrine therapy

  • No concurrent corticosteroids as anti-emetics


  • No concurrent radiotherapy


  • Not specified


  • At least 28 days since prior anticancer therapy and recovered
  • No other concurrent antineoplastic drugs
Sexes Eligible for Study: All
18 Years to 120 Years   (Adult, Senior)
Contact information is only displayed when the study is recruiting subjects
United States
CDR0000361734 ( Registry Identifier: PDQ (Physician Data Query) )
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Wake Forest University Health Sciences
Wake Forest University Health Sciences
National Cancer Institute (NCI)
Study Chair: Arthur E. Frankel, MD Wake Forest University Health Sciences
Wake Forest University Health Sciences
June 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP