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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00126646
Recruitment Status : Completed
First Posted : August 4, 2005
Last Update Posted : June 22, 2010
Information provided by:
MedImmune LLC

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.

Condition or disease Intervention/treatment Phase
Leukemia Lymphoma Drug: BL22 immunotoxin Procedure: antibody-drug conjugate therapy Procedure: immunotoxin therapy Phase 1

Detailed Description:


  • 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  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study of BL22, A Recombinant Immunotoxin for Chronic Lymphocytic Leukemia and CD22+ Lymphomas
Study Start Date : June 2005
Actual Primary Completion Date : March 2009
Actual Study Completion Date : June 2009

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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



  • 18 and over

Performance status

  • ECOG 0-2

Life expectancy

  • More than 6 months


  • 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


  • Bilirubin < 1.5 times upper limit of normal (ULN)
  • ALT and AST < 2.5 times ULN


  • Creatinine ≤ 1.5 mg/dL


  • FEV1 ≥ 60% of predicted
  • DLCO ≥ 55% of predicted


  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • HIV negative


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)


  • 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


  • 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


  • Not specified


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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00126646

United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
Bethesda, Maryland, United States, 20892-1182
Sponsors and Collaborators
MedImmune LLC
Principal Investigator: Robert Kreitman, MD National Cancer Institute (NCI)

Publications of Results:
Responsible Party: Robert Kreitman , MD, NCI Identifier: NCT00126646     History of Changes
Obsolete Identifiers: NCT00114751
Other Study ID Numbers: CDR0000438672
First Posted: August 4, 2005    Key Record Dates
Last Update Posted: June 22, 2010
Last Verified: June 2010

Keywords provided by MedImmune LLC:
B-cell chronic lymphocytic leukemia
refractory chronic lymphocytic leukemia
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
recurrent marginal zone lymphoma
splenic marginal zone lymphoma
stage III marginal zone lymphoma
stage IV marginal zone lymphoma
recurrent mantle cell lymphoma
stage III mantle cell lymphoma
stage IV mantle cell lymphoma
recurrent small lymphocytic lymphoma
stage III small lymphocytic lymphoma
stage IV small lymphocytic lymphoma
recurrent adult diffuse small cleaved cell lymphoma
stage III adult diffuse small cleaved cell lymphoma
stage IV adult diffuse small cleaved cell lymphoma
Waldenstrom macroglobulinemia
prolymphocytic leukemia

Additional relevant MeSH terms:
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Prolymphocytic
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Immunologic Factors
Physiological Effects of Drugs