Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Completed	18 and over	NCI, Pharmaceutical / Industry	CCCWFU-27102 CCCWFU-BG02-331, LIGAND-CCCWFU-27102, NCT00082940

Objectives

Primary

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

Secondary

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

Entry Criteria

Disease Characteristics:

• 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/mm³
  • 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

Prior/Concurrent Therapy:

Biologic therapy

• Prior denileukin diftitox allowed

Chemotherapy

• See Disease Characteristics

Endocrine therapy

• No concurrent corticosteroids as anti-emetics

Radiotherapy

• No concurrent radiotherapy

Surgery

• Not specified

Other

• At least 28 days since prior anticancer therapy and recovered
• No other concurrent antineoplastic drugs

Patient Characteristics:

Age

• 18 and over

Performance status

• Zubrod 0-2

Life expectancy

• More than 2 months

Hematopoietic

• Absolute neutrophil count ≥ 1,000/mm³
• Platelet count ≥ 50,000/mm³
• Hemoglobin ≥ 8 g/dL (transfusion allowed)

Hepatic

• 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

Renal

• Creatinine ≤ 1.5 mg/dL

  OR

• Creatinine clearance ≥ 40 mL/min

Cardiovascular

• LVEF ≥ 40%

Other

• 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

Expected Enrollment

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

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.

Frankel AE, Surendranathan A, Black JH, et al.: Phase II clinical studies of denileukin diftitox diphtheria toxin fusion protein in patients with previously treated chronic lymphocytic leukemia. Cancer 106 (10): 2158-64, 2006.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Wake Forest University Comprehensive Cancer Center

Arthur Frankel, MD, Protocol chair(Contact information may not be current)		Ph: 336-716-3313; 800-446-2255 Email: afrankel@wfubmc.edu

Registry Information
Official Title		A Phase II Study of ONTAK® (denileukin diftitox, DAB389IL-2) in Patients with Fludarabine-Refractory B-Cell Chronic Lymphocytic Leukemia
Trial Start Date		2002-08-21
Registered in ClinicalTrials.gov		NCT00082940
Date Submitted to PDQ		2004-03-11
Information Last Verified		2006-02-09
NCI Grant/Contract Number		P30-CA12197

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