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

This study has been completed.
National Cancer Institute (NCI)
Information provided by:
Comprehensive Cancer Center of Wake Forest University Identifier:
First received: May 14, 2004
Last updated: June 4, 2013
Last verified: June 2013

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.

Condition Intervention Phase
Biological: denileukin diftitox
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of ONTAK® (Denileukin Diftitox, DABIL-2) in Patients With Fludarabine-Refractory B-Cell Chronic Lymphocytic Leukemia

Resource links provided by NLM:

Further study details as provided by Comprehensive Cancer Center of Wake Forest University:

Study Start Date: August 2002
Study Completion Date: June 2005
Primary Completion Date: January 2005 (Final data collection date for primary outcome measure)
Detailed Description:



  • 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.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No


  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00082940

United States, California
St. Joseph Hospital Regional Cancer Center - Orange
Orange, California, United States, 92868-3849
United States, Illinois
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
Chicago, Illinois, United States, 60611
United States, Indiana
Medical Center Vincennes
Vincennes, Indiana, United States, 47591
United States, Louisiana
Cancer Care Specialists
Houma, Louisiana, United States, 70360
Feist-Weiller Cancer Center at Louisiana State University Health Sciences
Shreveport, Louisiana, United States, 71130-3932
United States, Michigan
Josephine Ford Cancer Center at Henry Ford Health System
Detroit, Michigan, United States, 48202
United States, North Carolina
Southeastern Medical Oncology Center
Goldsboro, North Carolina, United States, 27534
Comprehensive Cancer Center at Wake Forest University
Winston-Salem, North Carolina, United States, 27157-1082
United States, South Carolina
Gibbs Regional Cancer Center at Spartanburg Regional Medical Center
Spartanburg, South Carolina, United States, 29303
United States, Tennessee
Chattanooga Oncology and Hematology Associates
Chattanooga, Tennessee, United States, 37404
United States, Texas
Southwest Regional Cancer Center - Central
Austin, Texas, United States, 78705
Sponsors and Collaborators
Comprehensive Cancer Center of Wake Forest University
National Cancer Institute (NCI)
Study Chair: Arthur E. Frankel, MD Comprehensive Cancer Center of Wake Forest University
  More Information

Publications: Identifier: NCT00082940     History of Changes
Other Study ID Numbers: CCCWFU-27102  CDR0000361734  CCCWFU-BG02-331  LIGAND-CCCWFU-27102 
Study First Received: May 14, 2004
Last Updated: June 4, 2013
Health Authority: United States: Federal Government

Keywords provided by Comprehensive Cancer Center of Wake Forest University:
B-cell chronic lymphocytic leukemia
refractory chronic lymphocytic leukemia

Additional relevant MeSH terms:
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Immune System Diseases
Immunoproliferative Disorders
Leukemia, B-Cell
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms by Histologic Type
Denileukin diftitox
Analgesics, Non-Narcotic
Antineoplastic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Sensory System Agents processed this record on May 24, 2016