Immunotoxin Therapy in Treating Patients With Hairy Cell Leukemia

Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00021983
• Other study ID #: CDR0000066835
• Secondary ID: NCI-99-C-0014NCI
• Status: Completed
• Phase: Phase 1
• First received: August 10, 2001
• Last updated: April 28, 2015
• Start date: December 1998

Study information

• Verified date: January 2006
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

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.

Other known NCT identifiers

• NCT00001792

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Hairy Cell

Intervention

Biological:
• BL22 immunotoxin

Locations

Country	Name	City	State
United States	Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (3)

Kreitman RJ, Squires DR, Stetler-Stevenson M, Noel P, FitzGerald DJ, Wilson WH, Pastan I. Phase I trial of recombinant immunotoxin RFB4(dsFv)-PE38 (BL22) in patients with B-cell malignancies. J Clin Oncol. 2005 Sep 20;23(27):6719-29. Epub 2005 Aug 1. — View Citation

Kreitman RJ, Wilson WH, Bergeron K, Raggio M, Stetler-Stevenson M, FitzGerald DJ, Pastan I. Efficacy of the anti-CD22 recombinant immunotoxin BL22 in chemotherapy-resistant hairy-cell leukemia. N Engl J Med. 2001 Jul 26;345(4):241-7. — View Citation

Matsushita K, Margulies I, Onda M, Nagata S, Stetler-Stevenson M, Kreitman RJ. Soluble CD22 as a tumor marker for hairy cell leukemia. Blood. 2008 Sep 15;112(6):2272-7. doi: 10.1182/blood-2008-01-131987. Epub 2008 Jul 2. — View Citation