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

This study has been completed.
Sponsor:
Information provided by:
MedImmune LLC
ClinicalTrials.gov Identifier:
NCT00126646
First received: August 2, 2005
Last updated: June 17, 2010
Last verified: June 2010
  Purpose

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 Intervention Phase
Leukemia
Lymphoma
Drug: BL22 immunotoxin
Procedure: antibody-drug conjugate therapy
Procedure: immunotoxin therapy
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of BL22, A Recombinant Immunotoxin for Chronic Lymphocytic Leukemia and CD22+ Lymphomas

Resource links provided by NLM:


Further study details as provided by MedImmune LLC:

Estimated Enrollment: 24
Study Start Date: June 2005
Study Completion Date: June 2009
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00126646

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

Additional Information:
Publications:
Responsible Party: Robert Kreitman , MD, NCI
ClinicalTrials.gov Identifier: NCT00126646     History of Changes
Obsolete Identifiers: NCT00114751
Other Study ID Numbers: CDR0000438672, NCI-05-C-0171, NCI-P6620, NCI-5336
Study First Received: August 2, 2005
Last Updated: June 17, 2010
Health Authority: United States: Food and Drug Administration

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
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Leukemia, Prolymphocytic
Lymphoma
Immune System Diseases
Immunoproliferative Disorders
Leukemia, B-Cell
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Antibodies
Immunotoxins
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 23, 2014