• 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 ]

• 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

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.

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.

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