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

MedImmune

Status and phase: Completed; Phase 1

Conditions: Lymphoma; Leukemia

Treatments: Procedure: immunotoxin therapy; Drug: BL22 immunotoxin; Procedure: antibody-drug conjugate therapy

Study type: Interventional

Funder types: Industry

Identifiers

NCT00126646

NCI-P6620

CDR0000438672

NCI-05-C-0171

NCI-5336

Details and patient eligibility

About

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.

Full 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.

Enrollment: 24 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)