Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Related Information
Registry Information

Alternate Title

LMB-2 Immunotoxin in Treating Patients With Chronic Lymphocytic Leukemia or Prolymphocytic Leukemia

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Active 18 and over NCI NCI-04-C-0121 NCI-6074, 6074, NCT00080821

Special Category: NIH Clinical Center trial, NCI Web site featured trial

Objectives

Primary

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

Secondary

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

Entry 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/mm³) AND has at least one of the following:
    • Lymphadenopathy
    • Splenomegaly
    • Hepatomegaly
    • Anemia (hemoglobin < 11g/dL)
    • Thrombocytopenia (platelet count < 100,000/mm³)



• 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

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

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
• FEV₁ ≥ 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

Expected Enrollment

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

Outcomes

Response rate

Response duration
Correlation of blood levels with toxicity
Affect of the development of neutralizing antibodies on blood levels
Correlation of soluble Tac-peptide (sIL2Rα) levels with response

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.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

Robert Kreitman, MD, Protocol chair		Ph: 301-496-6947 Email: kreitmar@mail.nih.gov

U.S.A.
Maryland
	Bethesda
	Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
		Clinical Trials Office - Warren Grant Magnusen Clinical Center - NCI Clinical Trials Referral Office	Ph:  888-NCI-1937

Related Information

Web site for additional information
Featured trial article

Registry Information
Official Title		A Phase II Clinical Trial of Anti-Tac(Fv)-PE38 (LMB-2) Immunotoxin for Treatment of CD25 Positive Chronic Lymphocytic Leukemia
Trial Start Date		2004-02-09
Trial Completion Date		2005-03-20 (estimated)
Registered in ClinicalTrials.gov		NCT00080821
Date Submitted to PDQ		2004-02-09
Information Last Verified		2008-05-20

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