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LMB-2 Immunotoxin in Treating Patients With Chronic Lymphocytic Leukemia or Prolymphocytic Leukemia
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), May 2008
Sponsored by: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00080821
  Purpose

RATIONALE: LMB-2 immunotoxin can locate cancer cells and kill them without harming normal cells. This may be effective treatment for chronic lymphocytic leukemia or prolymphocytic leukemia.

PURPOSE: This phase II trial is studying how well LMB-2 immunotoxin works in treating patients with chronic lymphocytic leukemia or prolymphocytic leukemia.


Condition Intervention Phase
Leukemia
Drug: LMB-2 immunotoxin
Phase II

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic
Drug Information available for: Dacliximab
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Open Label
Official Title: A Phase II Clinical Trial of Anti-Tac(Fv)-PE38 (LMB-2) Immunotoxin for Treatment of CD25 Positive Chronic Lymphocytic Leukemia

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Response rate [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Response duration [ Designated as safety issue: No ]
  • Correlation of blood levels with toxicity [ Designated as safety issue: Yes ]
  • Affect of the development of neutralizing antibodies on blood levels [ Designated as safety issue: No ]
  • Correlation of soluble Tac-peptide (sIL2Rα) levels with response [ Designated as safety issue: No ]

Estimated Enrollment: 27
Study Start Date: February 2004
Estimated Primary Completion Date: March 2005 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • Determine the response rate in patients with CD25-positive chronic lymphocytic leukemia or prolymphocytic leukemia treated with LMB-2 immunotoxin.

Secondary

  • Determine the response duration in patients treated with this drug.
  • Correlate blood levels of this drug with toxicity in these patients.
  • Determine how the development of neutralizing antibodies affects blood levels of this drug and toxicity in these patients.
  • Correlate soluble Tac-peptide (slL2Rα) levels with response in patients treated with this drug.

OUTLINE: Patients receive LMB-2 immunotoxin IV over 30 minutes on days 1, 3, and 5. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression, neutralizing antibodies (i.e., > 75% of the activity of 1µg/mL of LMB-2 immunotoxin), or unacceptable toxicity.

Patients who achieve a complete response receive up to 2 additional courses of LMB-2 immunotoxin. Patients who relapse after achieving a complete or partial response for more than 2 months are eligible for retreatment as described above.

Patients are followed every 3-12 months until disease progression.

PROJECTED ACCRUAL: A total of 16-27 patients will be accrued for this study within 2 years.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically confirmed chronic lymphocytic leukemia, including prolymphocytic leukemia
  • CD25-positive disease

    • At least 50% of peripheral malignant lymphocytes are CD25+ by fluorescence-activated cell sorting (FACS) with anti-CD25 antibody* NOTE: *Positive expression in FACS assay is defined as > 2 times the mean fluorescence intensity of the control antibody by FACS
  • Intermediate- or high-risk disease, meeting the following criteria:

    • Lymphocytosis (leukemic cells > 5,000/mm^3) AND has at least one of the following:

      • Lymphadenopathy
      • Splenomegaly
      • Hepatomegaly
      • Anemia (hemoglobin < 11g/dL)
      • Thrombocytopenia (platelet count < 100,000/mm^3)
  • Progressive disease after prior standard therapy containing either a purine analog or an alkylating agent
  • No serum neutralizing LMB-2 immunotoxin in tissue culture (due to either anti-toxin or anti-mouse-immunoglobulin G antibodies)
  • No serum neutralizing > 75% of the activity of 1μg/mL of LMB-2 immunotoxin

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • ECOG 0-2

Life expectancy

  • Not specified

Hematopoietic

  • See Disease Characteristics

Hepatic

  • See Disease Characteristics
  • ALT and AST ≤ 2.5 times upper limit of normal (ULN)
  • Albumin ≥ 3.0 g/dL
  • Bilirubin ≤ 2.2 mg/dL (< 5 mg/dL in patients with Gilbert's syndrome)
  • Hepatitis B surface antigen negative unless patient is receiving treatment with lamivudine
  • No hepatitis C
  • No chronic liver disease

Renal

  • Creatinine ≤ 1.4 mg/dL OR
  • Creatinine clearance ≥ 50 mL/min

Cardiovascular

  • LVEF ≥ lower limit of normal
  • No symptomatic congestive heart failure
  • No unstable angina pectoris
  • No cardiac arrhythmia

Pulmonary

  • DLCO ≥ 55% of normal
  • FEV_1 ≥ 60% of normal

Other

  • No ongoing or active infection
  • No other active cancer requiring treatment
  • No other concurrent uncontrolled illness
  • No psychiatric illness or social situation that would preclude study compliance
  • HIV negative
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective barrier contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • More than 4 weeks since prior monoclonal antibody therapy
  • No prior LMB-2 immunotoxin

Chemotherapy

  • See Disease Characteristics
  • More than 4 weeks since prior systemic cytotoxic chemotherapy

Endocrine therapy

  • More than 4 weeks since prior systemic steroids except stable doses of prednisone of ≤ 20 mg/day

Radiotherapy

  • Not specified

Surgery

  • Not specified

Other

  • No concurrent warfarin for anticoagulation
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00080821

Locations
United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office Recruiting
Bethesda, Maryland, United States, 20892-1182
Contact: Clinical Trials Office - Warren Grant Magnusen Clinical Center     888-NCI-1937        
Sponsors and Collaborators
Investigators
Study Chair: Robert Kreitman, MD National Cancer Institute (NCI)
  More Information

Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site
Web site for additional information  This link exits the ClinicalTrials.gov site
Featured trial article  This link exits the ClinicalTrials.gov site

Study ID Numbers: CDR0000355837, NCI-04-C-0121, NCI-6074
Study First Received: April 7, 2004
Last Updated: December 11, 2008
ClinicalTrials.gov Identifier: NCT00080821  
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
refractory chronic lymphocytic leukemia
stage I chronic lymphocytic leukemia
stage II chronic lymphocytic leukemia
stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia
prolymphocytic leukemia

Study placed in the following topic categories:
Chronic lymphocytic leukemia
Leukemia, Lymphoid
Immunoproliferative Disorders
Leukemia, B-cell, chronic
Daclizumab
Immunotoxins
Antibodies, Monoclonal
Leukemia
Lymphatic Diseases
Antibodies
Leukemia, Prolymphocytic
Leukemia, Lymphocytic, Chronic, B-Cell
Prolymphocytic leukemia
Leukemia, B-Cell
Lymphoproliferative Disorders
Immunoglobulins

Additional relevant MeSH terms:
Neoplasms
Neoplasms by Histologic Type
Immunologic Factors
Immune System Diseases
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009