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506U78 in Treating Patients With Chronic Lymphocytic Leukemia That Has Not Responded to Fludarabine or Alkylating Agents

Primary Purpose

Leukemia

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
nelarabine
Sponsored by
GlaxoSmithKline
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia focused on measuring refractory chronic lymphocytic leukemia, T-cell large granular lymphocyte leukemia, B-cell chronic lymphocytic leukemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS: Diagnosis of refractory chronic lymphocytic leukemia Evidence of active disease after fludarabine or alkylator therapy Must meet one or more of the following criteria for active disease: Minimum of one of the following disease-related symptoms: Weight loss of 10% or more within the previous 6 months Extreme fatigue (e.g., unable to work or perform usual activities) Fevers greater than 100.5 degrees F for 2 weeks or more without evidence of infection Night sweats without evidence of infection Evidence of progressive marrow failure manifested by the development or worsening of autoimmune anemia and/or thrombocytopenia that is poorly responsive to corticosteroid therapy Massive (e.g., greater than 6 cm below the left costal margin) or progressive splenomegaly Massive nodes or clusters (e.g., greater than 10 cm in longest diameter) or progressive lymphadenopathy Progressive lymphocytosis with an increase of more than 50% over a 2-month period or an anticipated doubling time of less than 6 months Ineligible if marked hypogammaglobulinemia or development of monoclonal protein in the absence of the above criteria for active disease Must have one of the following resulting from prior fludarabine or alkylator-containing therapy: Disease progression during therapy Failure to respond or obtained less than a partial response to therapy Disease progression within 6 months of the last course of therapy after an initial response Failure to respond or disease progression allowed at any time after the final dose if alkylator agent was not the most recent therapy PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 60-100% Life expectancy: At least 12 weeks Hematopoietic: See Disease Characteristics Hepatic: See Disease Characteristics Bilirubin no greater than 2 times upper limit of normal No liver dysfunction due to organ infiltration by lymphocytes Renal: Creatinine clearance at least 50 mL/min Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for up to 28 days after study No neurotoxicity of grade 2 or higher No history of significant neurologic toxicity (grade 2 or greater motor or sensory impairment) due to prior chemotherapy or radiotherapy No history of seizure disorder No active infection No other malignancy within the past 2 years (except adequately treated non- melanomatous skin cancer or carcinoma in situ) that would preclude study No systemic nonmalignant comorbid disease that would preclude study No psychological, sociological, or geographical condition that would preclude study PRIOR CONCURRENT THERAPY: Biologic therapy: No prior bone marrow or peripheral blood stem cell transplantation Recovered from prior immunotherapy At least 4 weeks since prior biologic therapy and recovered Concurrent growth factors allowed Chemotherapy: See Disease Characteristics At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered No prior 506U78 therapy No other concurrent chemotherapy Endocrine therapy: See Disease Characteristics No concurrent corticosteroid therapy greater than 10 mg/day of prednisone equivalent No concurrent corticosteroids as antiemetics Concurrent hormone replacement therapy or oral contraceptives allowed Concurrent hydrocortisone as prophylaxis or treatment of transfusion reactions allowed Radiotherapy: At least 4 weeks since prior radiotherapy and recovered No concurrent radiotherapy Surgery: Not specified Other: No other concurrent anticancer agents

Sites / Locations

  • University of Alabama at Birmingham Comprehensive Cancer Center
  • Arizona Cancer Center
  • University of Arkansas for Medical Sciences
  • Scripps Clinic
  • Cedars-Sinai Medical Center
  • Jonsson Comprehensive Cancer Center, UCLA
  • Sidney Kimmel Cancer Center
  • Clinical Studies, Ltd.
  • Lombardi Cancer Center
  • Walter Reed Army Medical Center
  • Robert H. Lurie Comprehensive Cancer Center, Northwestern University
  • University of Chicago Cancer Research Center
  • Holden Comprehensive Cancer Center at The University of Iowa
  • Johns Hopkins Oncology Center
  • Medicine Branch
  • Washington University School of Medicine
  • St. Joseph's Hospital and Medical Center
  • Long Island Jewish Medical Center
  • Ireland Cancer Center
  • Greenville Hospital System
  • Physician Reliance Network, Inc.
  • University of Texas - MD Anderson Cancer Center

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 1, 1999
Last Updated
July 17, 2013
Sponsor
GlaxoSmithKline
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00003635
Brief Title
506U78 in Treating Patients With Chronic Lymphocytic Leukemia That Has Not Responded to Fludarabine or Alkylating Agents
Official Title
A Multicenter Study to Assess the Efficacy of 506U78 in Patients With Chronic Lymphocytic Leukemia Who Are Refractory to Fludarabine and Alkylator Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
January 2002
Overall Recruitment Status
Completed
Study Start Date
January 1999 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
March 2004 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
GlaxoSmithKline
Collaborators
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. PURPOSE: Phase II trial to study the effectiveness of 506U78 in treating patients with chronic lymphocytic leukemia that has not responded to fludarabine or alkylating agents.
Detailed Description
OBJECTIVES: I. Determine the anticancer efficacy of 506U78 in patients with chronic lymphocytic leukemia refractory to fludarabine and alkylator therapy. II. Determine the safety (including incidence of infection) of this drug in these patients. III. Evaluate the pharmacokinetics of 506U78 and ara-G, and assess the intracellular pharmacokinetics of ara-GTP in patients receiving multiple treatment courses (at M.D. Anderson Cancer Center only). IV. Determine the response rate, time to maximal response, and duration of response in patients treated with this drug. V. Determine two-year survival and progression-free survival of patients treated with this drug. OUTLINE: This is a multicenter study. Patients are stratified according to cellular type of disease (B cell vs T cell). Patients receive 506U78 IV over 2 hours on days 1, 3, and 5. Treatment repeats every 28 days for a maximum of 8 courses in the absence of disease progression or unacceptable toxicity. Patients are followed at 28 days and then every 2 months for 2 years until disease progression. After disease progression, patients are followed every 3 months for 2 years. PROJECTED ACCRUAL: Approximately 14-100 patients will be accrued for this study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia
Keywords
refractory chronic lymphocytic leukemia, T-cell large granular lymphocyte leukemia, B-cell chronic lymphocytic leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
nelarabine

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Diagnosis of refractory chronic lymphocytic leukemia Evidence of active disease after fludarabine or alkylator therapy Must meet one or more of the following criteria for active disease: Minimum of one of the following disease-related symptoms: Weight loss of 10% or more within the previous 6 months Extreme fatigue (e.g., unable to work or perform usual activities) Fevers greater than 100.5 degrees F for 2 weeks or more without evidence of infection Night sweats without evidence of infection Evidence of progressive marrow failure manifested by the development or worsening of autoimmune anemia and/or thrombocytopenia that is poorly responsive to corticosteroid therapy Massive (e.g., greater than 6 cm below the left costal margin) or progressive splenomegaly Massive nodes or clusters (e.g., greater than 10 cm in longest diameter) or progressive lymphadenopathy Progressive lymphocytosis with an increase of more than 50% over a 2-month period or an anticipated doubling time of less than 6 months Ineligible if marked hypogammaglobulinemia or development of monoclonal protein in the absence of the above criteria for active disease Must have one of the following resulting from prior fludarabine or alkylator-containing therapy: Disease progression during therapy Failure to respond or obtained less than a partial response to therapy Disease progression within 6 months of the last course of therapy after an initial response Failure to respond or disease progression allowed at any time after the final dose if alkylator agent was not the most recent therapy PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 60-100% Life expectancy: At least 12 weeks Hematopoietic: See Disease Characteristics Hepatic: See Disease Characteristics Bilirubin no greater than 2 times upper limit of normal No liver dysfunction due to organ infiltration by lymphocytes Renal: Creatinine clearance at least 50 mL/min Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for up to 28 days after study No neurotoxicity of grade 2 or higher No history of significant neurologic toxicity (grade 2 or greater motor or sensory impairment) due to prior chemotherapy or radiotherapy No history of seizure disorder No active infection No other malignancy within the past 2 years (except adequately treated non- melanomatous skin cancer or carcinoma in situ) that would preclude study No systemic nonmalignant comorbid disease that would preclude study No psychological, sociological, or geographical condition that would preclude study PRIOR CONCURRENT THERAPY: Biologic therapy: No prior bone marrow or peripheral blood stem cell transplantation Recovered from prior immunotherapy At least 4 weeks since prior biologic therapy and recovered Concurrent growth factors allowed Chemotherapy: See Disease Characteristics At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered No prior 506U78 therapy No other concurrent chemotherapy Endocrine therapy: See Disease Characteristics No concurrent corticosteroid therapy greater than 10 mg/day of prednisone equivalent No concurrent corticosteroids as antiemetics Concurrent hormone replacement therapy or oral contraceptives allowed Concurrent hydrocortisone as prophylaxis or treatment of transfusion reactions allowed Radiotherapy: At least 4 weeks since prior radiotherapy and recovered No concurrent radiotherapy Surgery: Not specified Other: No other concurrent anticancer agents
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tonya M. Peele, MS
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Chair
Facility Information:
Facility Name
University of Alabama at Birmingham Comprehensive Cancer Center
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294-3300
Country
United States
Facility Name
Arizona Cancer Center
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85724
Country
United States
Facility Name
University of Arkansas for Medical Sciences
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States
Facility Name
Scripps Clinic
City
La Jolla
State/Province
California
ZIP/Postal Code
92037
Country
United States
Facility Name
Cedars-Sinai Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
Jonsson Comprehensive Cancer Center, UCLA
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095-1781
Country
United States
Facility Name
Sidney Kimmel Cancer Center
City
San Diego
State/Province
California
ZIP/Postal Code
92121
Country
United States
Facility Name
Clinical Studies, Ltd.
City
Denver
State/Province
Colorado
ZIP/Postal Code
80222
Country
United States
Facility Name
Lombardi Cancer Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Facility Name
Walter Reed Army Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20307-5000
Country
United States
Facility Name
Robert H. Lurie Comprehensive Cancer Center, Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611-3013
Country
United States
Facility Name
University of Chicago Cancer Research Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637-1470
Country
United States
Facility Name
Holden Comprehensive Cancer Center at The University of Iowa
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242-1009
Country
United States
Facility Name
Johns Hopkins Oncology Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231-2410
Country
United States
Facility Name
Medicine Branch
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
St. Joseph's Hospital and Medical Center
City
Paterson
State/Province
New Jersey
ZIP/Postal Code
07503
Country
United States
Facility Name
Long Island Jewish Medical Center
City
New Hyde Park
State/Province
New York
ZIP/Postal Code
11040
Country
United States
Facility Name
Ireland Cancer Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106-5065
Country
United States
Facility Name
Greenville Hospital System
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29605
Country
United States
Facility Name
Physician Reliance Network, Inc.
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Facility Name
University of Texas - MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030-4009
Country
United States

12. IPD Sharing Statement

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506U78 in Treating Patients With Chronic Lymphocytic Leukemia That Has Not Responded to Fludarabine or Alkylating Agents

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