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

NCT ID: NCT00126646

Last Updated: 2010-06-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-06-30
• Study Completion Date: 2009-06-30

Brief 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.

Detailed 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.

Conditions

Leukemia; Lymphoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

BL22 immunotoxin

Intervention Type: DRUG

antibody-drug conjugate therapy

Intervention Type: PROCEDURE

immunotoxin therapy

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

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

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

Sponsors

MedImmune LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

NCI

Principal Investigators

Robert Kreitman, MD

Role: PRINCIPAL_INVESTIGATOR

National Cancer Institute (NCI)

Locations

Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office

Bethesda, Maryland, United States

Countries

United States

References

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: RESULT

PMID: 16061911 (View on PubMed)

Other Identifiers

NCI-05-C-0171

Identifier Type: -

Identifier Source: secondary_id

NCI-P6620

Identifier Type: -

Identifier Source: secondary_id

NCI-5336

Identifier Type: -

Identifier Source: secondary_id

CDR0000438672

Identifier Type: -

Identifier Source: org_study_id

NCT00114751

Identifier Type: -

Identifier Source: nct_alias