BL22 Immunotoxin in Treating Patients With Refractory Chronic Lymphocytic Leukemia, Prolymphocytic Leukemia, or Non-Hodgkin's Lymphoma

Lymphoma Clinical Trial

Official title:

Phase I Study of BL22, A Recombinant Immunotoxin for Chronic Lymphocytic Leukemia and CD22+ Lymphomas

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00126646
• Other study ID #: CDR0000438672
• Secondary ID: NCI-05-C-0171NCI
• Status: Completed
• Phase: Phase 1
• First received: August 2, 2005
• Last updated: June 17, 2010
• Start date: June 2005
• Est. completion date: June 2009

Study information

• Verified date: June 2010
• Source: MedImmune LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

RATIONALE: BL22 immunotoxin can find tumor cells and kill them without harming normal cells.

PURPOSE: This phase I trial is studying the side effects and best dose of BL22 immunotoxin in treating patients with refractory B-cell chronic lymphocytic leukemia, prolymphocytic leukemia, or non-Hodgkin's lymphoma.

Description:

OBJECTIVES:

• Determine the maximum tolerated dose of recombinant BL22 immunotoxin in patients with CD22-positive refractory B-cell chronic lymphocytic leukemia, prolymphocytic leukemia, or indolent non-Hodgkin's lymphoma.

• Determine the safety and efficacy of this drug in these patients.

• Determine the pharmacokinetics of this drug in these patients.

• Determine 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 nonrandomized, dose-escalation study. Patients are stratified according to disease type (chronic lymphocytic leukemia vs non-Hodgkin's lymphoma).

Patients receive recombinant BL22 immunotoxin IV over 30 minutes on days 1, 3, and 5. Treatment repeats ≥ every 27 days for up to 6 courses in the absence of neutralizing antibodies to BL22 or PE38, disease progression, or unacceptable toxicity. Patients achieving a complete response (CR) receive 2 additional courses beyond CR. Patients who relapse from a CR lasting ≥ 6 months may receive additional courses.

Cohorts of 3-6 patients per stratum receive escalating doses of recombinant BL22 immunotoxin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: A total of 24 patients (12 per stratum) will be accrued for this study within 1-2 years.

Other known NCT identifiers

• NCT00114751

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: June 2009
• Est. primary completion date: March 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Diagnosis of B-cell leukemia or lymphoma of 1 of the following types:

• Chronic lymphocytic leukemia

• Failed standard chemotherapy

• Prolymphocytic leukemia

• Failed standard chemotherapy

• Indolent non-Hodgkin's lymphoma, including mantle cell lymphoma

• Stage III or IV disease

• Failed = 1 prior doxorubicin- or fludarabine-containing standard therapy

• CD22-positive disease, as evidenced by 1 of the following:

• More than 15% malignant cells react with anti-CD22 by immunohistochemistry

• More than 30% malignant cells are CD22-positive by fluorescence-activated cell sorting analysis

• More than 400 CD22 sites per malignant cell (average) by radiolabeled anti-CD22 binding

• Treatment is medically indicated, as evidenced by any of the following:

• Progressive disease-related symptoms

• Progressive cytopenias due to marrow involvement

• Progressive or painful splenomegaly or adenopathy

• Rapidly increasing lymphocytosis

• Autoimmune hemolytic anemia or thrombocytopenia

• Increased frequency of infections

• No neutralizing anti-toxin or anti-mouse immunoglobulin G (IgG) antibodies to BL22 or PE38

• No serum neutralization of > 75% of the activity of 1 µg/mL of BL22

• No CNS disease requiring treatment

• No hairy cell leukemia

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• More than 6 months

Hematopoietic

• Absolute neutrophil count > 1,000/mm^3*

• Platelet count > 40,000/mm^3 NOTE: *Patients with leukemia are eligible regardless of absolute neutrophil count; Grade III-IV pancytopenia or growth factor dependence allowed if due to disease

Hepatic

• Bilirubin < 1.5 times upper limit of normal (ULN)

• ALT and AST < 2.5 times ULN

Renal

• Creatinine = 1.5 mg/dL

Pulmonary

• FEV1 = 60% of predicted

• DLCO = 55% of predicted

Other

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Prior bone marrow transplantation allowed

• More than 3 weeks since prior biologic therapy, including interferon, denileukin diftitox, or LMB-2 immunotoxin

• More than 3 months since prior monoclonal antibody therapy (e.g., rituximab)

Chemotherapy

• See Disease Characteristics

• More than 3 weeks since prior cytotoxic chemotherapy

Endocrine therapy

• More than 1 week since prior steriods

• Less than 5 doses for non-treatment reasons (e.g., allergy prophylaxis)

• No evidence of disease response

Radiotherapy

• More than 3 weeks since prior whole-body electron beam radiotherapy

• Radiotherapy within the past 3 weeks allowed provided the volume of bone marrow treated is < 10% AND the patient has measurable disease located outside the radiation port

Surgery

• Not specified

Other

• More than 3 weeks since prior retinoids

• More than 3 weeks since other prior systemic therapy for this malignancy

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Leukemia, Prolymphocytic
• Lymphoma

Intervention

Drug:
• BL22 immunotoxin

Procedure:
• antibody-drug conjugate therapy

• immunotoxin therapy

Locations

Country	Name	City	State
United States	Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
MedImmune LLC

Country where clinical trial is conducted

United States, 

References & Publications (1)

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