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

Leukemia Clinical Trial

Official title:

A Phase II Study of ONTAK® (Denileukin Diftitox, DABIL-2) in Patients With Fludarabine-Refractory B-Cell Chronic Lymphocytic Leukemia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00082940
• Other study ID #: CCCWFU-27102
• Secondary ID: CDR0000361734CCC
• Status: Completed
• Phase: Phase 2
• First received: May 14, 2004
• Last updated: January 17, 2017
• Start date: August 2002
• Est. completion date: June 2005

Study information

• Verified date: June 2013
• Source: Wake Forest University Health Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

OBJECTIVES:

Primary

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

Secondary

• 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. completion date: June 2005
• Est. primary completion date: January 2005
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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/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

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Zubrod 0-2

Life expectancy

• More than 2 months

Hematopoietic

• Absolute neutrophil count = 1,000/mm^3

• Platelet count = 50,000/mm^3

• 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

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

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid

Intervention

Biological:
• denileukin diftitox

Locations

Country	Name	City	State
United States	Southwest Regional Cancer Center - Central	Austin	Texas
United States	Chattanooga Oncology and Hematology Associates	Chattanooga	Tennessee
United States	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois
United States	Josephine Ford Cancer Center at Henry Ford Health System	Detroit	Michigan
United States	Southeastern Medical Oncology Center	Goldsboro	North Carolina
United States	Cancer Care Specialists	Houma	Louisiana
United States	St. Joseph Hospital Regional Cancer Center - Orange	Orange	California
United States	Feist-Weiller Cancer Center at Louisiana State University Health Sciences	Shreveport	Louisiana
United States	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina
United States	Medical Center Vincennes	Vincennes	Indiana
United States	Comprehensive Cancer Center at Wake Forest University	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Wake Forest University Health Sciences	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation