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Phase I Study of BL22, a Recombinant Immunotoxin for Treatment of CD22+ Leukemias and Lymphomas


Phase 1
18 Years
N/A
Not Enrolling
Both
Leukemia

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Trial Information

Phase I Study of BL22, a Recombinant Immunotoxin for Treatment of CD22+ Leukemias and Lymphomas


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Principal Investigator

Robert Kreitman, MD

Investigator Role:

Study Chair

Investigator Affiliation:

National Cancer Institute (NCI)

Authority:

United States: Federal Government

Study ID:

CDR0000066835

NCT ID:

NCT00021983

Start Date:

December 1998

Completion Date:

Related Keywords:

  • Leukemia
  • refractory hairy cell leukemia
  • Leukemia
  • Leukemia, Hairy Cell

Name

Location

Warren Grant Magnuson Clinical Center - NCI Clinical Studies SupportBethesda, Maryland  20892-1182