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

Phase 1
18 Years
Not Enrolling
Leukemia, Lymphoma

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Trial Information

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


- 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.

Inclusion Criteria


- 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

- 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

- 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

Type of Study:


Study Design:

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

Principal Investigator

Robert Kreitman, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Institute (NCI)


United States: Food and Drug Administration

Study ID:




Start Date:

June 2005

Completion Date:

June 2009

Related Keywords:

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



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