Immunotoxin Therapy in Treating Patients With Hairy Cell Leukemia

National Cancer Institute (NCI)

Status and phase: Completed; Phase 1

Conditions: Leukemia

Treatments: Biological: BL22 immunotoxin

Study type: Interventional

Funder types: NIH

Identifiers

NCT00021983

CDR0000066835

NCI-T98-0063

NCI-99-C-0014

Details and patient eligibility

About

RATIONALE: An immunotoxin can locate cancer cells and kill them without harming normal cells. This may be an effective treatment for hairy cell leukemia.

PURPOSE: Phase I trial to study the effectiveness of BL22 immunotoxin in treating patients who have refractory or recurrent hairy cell leukemia.

Full description

OBJECTIVES:

• Assess the toxicity and therapeutic efficacy of recombinant BL22 immunotoxin in patients with refractory or recurrent CD22+ hairy cell leukemia.
• Define the pharmacokinetics of this drug, including the terminal elimination serum half-life area under the curve and volume of distribution, in these patients.
• Evaluate the immunogenicity of this drug in these patients.
• Determine the effect of this drug on various components of the circulating cellular immune system in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive recombinant BL22 immunotoxin IV over 30 minutes on days 1, 3, and 5. Treatment repeats at least every 42 days for up to 4 courses in the absence of disease progression and sufficient neutralizing antibodies.

Cohorts of 3-6 patients receive escalating doses of recombinant BL22 immunotoxin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which no more than 1 of 6 patients experiences dose-limiting toxicity.

PROJECTED ACCRUAL: A maximum of 46 patients will be accrued for this study within 3 years.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed refractory or recurrent hairy cell leukemia

  • Relapsed after less than 2 years of complete remission after purine analog therapy

  • Must have at least one of the following indications for therapy:

    • Progressive or massive splenomegaly

    • Cytopenia defined by the following:

      • Absolute neutrophil count less than 1,000/mm^3 OR
      • Platelet count less than 100,000/mm^3 OR
      • Hemoglobin less than 12 g/dL

    • More than 20,000 hairy cells/mm^3

    • Symptomatic adenopathy

    • Constitutional symptoms including tumor-related fever or bone pain

• Evidence of CD22 positivity by 1 of the following:

  • More than 15% of malignant cells from a site must react with anti-CD22 by immunohistochemistry
  • More than 30% of malignant cells from a site CD22+ by fluorescent-activated cell sorter
  • More than 400 CD22 sites/cell (average) on malignant cells as assessed by radiolabeled anti-CD22 binding

• No CNS disease requiring treatment

• No patients whose serum neutralizes BL22 immunotoxin in tissue culture, due to either antitoxin or antimouse-IgG antibodies

  • No patients whose serum neutralizes more than 75% of the activity of 1 microgram/mL of BL22 immunotoxin

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Karnofsky 60-100%

Life expectancy:

• More than 6 months

Hematopoietic:

• See Disease Characteristics
• Pancytopenia due to disease allowed

Hepatic:

• ALT and AST less than 2.5 times upper limit of normal (ULN)
• Bilirubin less than 1.5 times ULN

Renal:

• Creatinine no greater than 2.0 mg/dL

Pulmonary:

• FEV1 at least 60% of predicted
• DLCO at least 55% of predicted

Other:

• HIV negative
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Prior bone marrow transplantation allowed
• At least 3 weeks since prior interferon for the malignancy
• More than 3 months since prior monoclonal antibody therapy (e.g., rituximab)

Chemotherapy:

• See Disease Characteristics
• At least 3 weeks since prior cytotoxic chemotherapy for the malignancy

Endocrine therapy:

• Not specified

Radiotherapy:

• At least 3 weeks since prior whole body electron beam radiotherapy for the malignancy
• Radiotherapy within the past 3 weeks allowed provided less than 10% of total bone marrow was treated and patient has measurable disease outside the radiation port

Surgery:

• Not specified

Other:

• At least 3 weeks since prior retinoids for the malignancy
• At least 3 weeks since any other prior systemic therapy for the malignancy
• No concurrent therapeutic warfarin