Immunotoxin Therapy in Treating Patients With Hairy Cell Leukemia

NCT ID: NCT00021983

Last Updated: 2015-04-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 1998-12-31

Brief 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.

Detailed 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.

Conditions

Leukemia

Study Design

• Primary Study Purpose: TREATMENT

Interventions

BL22 immunotoxin

Intervention Type: BIOLOGICAL

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Principal Investigators

Robert Kreitman, MD

Role: STUDY_CHAIR

National Cancer Institute (NCI)

Locations

Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support

Bethesda, Maryland, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 18596230 (View on PubMed)

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. doi: 10.1200/JCO.2005.11.437. Epub 2005 Aug 1.

Reference Type: BACKGROUND

PMID: 16061911 (View on PubMed)

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. doi: 10.1056/NEJM200107263450402.

Reference Type: RESULT

PMID: 11474661 (View on PubMed)

Other Identifiers

NCI-99-C-0014

Identifier Type: -

Identifier Source: secondary_id

NCI-T98-0063

Identifier Type: -

Identifier Source: secondary_id

CDR0000066835

Identifier Type: -

Identifier Source: org_study_id

NCT00001792

Identifier Type: -

Identifier Source: nct_alias