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

June 17, 2010 updated by: MedImmune LLC

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

24

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20892-1182
        • Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

MedImmune LLC

Investigators

  • Principal Investigator: Robert Kreitman, MD, National Cancer Institute (NCI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2005

Primary Completion (ACTUAL)

March 1, 2009

Study Completion (ACTUAL)

June 1, 2009

Study Registration Dates

First Submitted

August 2, 2005

First Submitted That Met QC Criteria

August 2, 2005

First Posted (ESTIMATE)

August 4, 2005

Study Record Updates

Last Update Posted (ESTIMATE)

June 22, 2010

Last Update Submitted That Met QC Criteria

June 17, 2010

Last Verified

June 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000438672
  • NCI-05-C-0171
  • NCI-P6620
  • NCI-5336

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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