protocol development and Amended protocol revision

RATIONALE: BL22 immunotoxin can locate tumor cells and kill them without harming normal cells. BL22 immunotoxin may be effective in treating relapsed or refractory acute lymphoblastic leukemia and non-Hodgkin's lymphoma.

PURPOSE: This phase I trial is studying the side effects and best dose of BL22 immunotoxin in treating young patients with relapsed or refractory acute lymphoblastic leukemia or non-Hodgkin's lymphoma.

OBJECTIVES:

Primary

• Determine the toxic effects of BL22 immunotoxin in pediatric patients with relapsed or refractory CD22-positive acute lymphoblastic leukemia or non-Hodgkin's lymphoma.
• Determine the maximum tolerated dose of this drug in these patients.
• Determine the immunogenicity of this drug in these patients.
• Determine the pharmacokinetics of this drug in these patients.

Secondary

• Determine the in vitro cytotoxicity of this drug against lymphoblasts from patients with acute lymphoblastic leukemia.
• Determine the therapeutic efficacy of this drug in inducing remissions in these patients.
• Determine changes in lymphocyte subsets, immunoglobulin levels, serum cytokines, and soluble cytokine receptor levels in patients treated with this drug.

OUTLINE: This is a non-randomized, dose-escalation study.

Patients receive BL22 immunotoxin IV over 30 minutes on days 1, 3, and 5 OR on days 1, 3, 5, 7, 9, and 11. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve a complete response (CR) or unconfirmed CR (CRu) receive 2 additional courses beyond CR or CRu for a maximum of 6 courses.

Cohorts of 3-6 patients receive escalating doses of 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. Once the MTD is determined, the cohort is expanded and a total of 12 patients are treated at that dose.

Patients are followed weekly for at least 1 month and then every 1-3 months thereafter.

PROJECTED ACCRUAL: A total of 95 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed acute lymphoblastic leukemia (ALL) or non-Hodgkin's lymphoma (including lymphoblastic lymphoma, Burkitt's lymphoma, and large cell lymphoma)

  • Not amenable to available curative therapies

• Relapsed or refractory disease after at least 1 standard chemotherapy and 1 salvage regimen

• CD22 positive according to at least 1 of the following criteria:

  • More than 15% CD22-positive malignant cells by immunohistochemistry
  • More than 30% CD22-positive malignant cells by fluorescent-activated cell sorter analysis

• Measurable or evaluable disease

• Prior CNS involvement allowed provided there is no current evidence of CNS malignancy

• No CNS leukemia or lymphoma as manifested by any of the following:

  • Cerebrospinal fluid (CSF) WBC ≥ 5/mm^3 and confirmation of CSF blasts
  • Cranial neuropathies secondary to underlying malignancy
  • Radiologically detected CNS lymphoma

• No isolated testicular ALL

• Ineligible for or refused hematopoietic stem cell transplantation OR has disease activity that prohibits the time required to identify a suitable stem cell donor

PATIENT CHARACTERISTICS:

Age

• 6 months to 24 years

Performance status

• ECOG 0-3 (12 to 24 years of age)
• Lansky 40-100% (under 12 years of age)

Life expectancy

• Not specified

Hematopoietic

• See Disease Characteristics
• Absolute neutrophil count > 1,000/mm^3 *
• Platelet count > 50,000/mm^3 * NOTE: *Non-leukemic patients only

Hepatic

• Bilirubin ≤ 2.0 mg/dL
• AST and ALT ≤ 5 times upper limit of normal
• No active hepatitis B or C infection

Renal

• Creatinine normal for age OR
• Creatinine clearance ≥ 60 mL/min

Immunologic

• No serum neutralization of more than 75% of the activity of 1 µg/mL of study drug
• HIV negative

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No clinically significant unrelated systemic illness that would preclude study participation
• No other significant organ dysfunction that would preclude study participation
• No psychiatric illness or social situation that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics
• At least 1 week since prior colony-stimulating factors (e.g., filgrastim [G-CSF], sargramostim [GM-CSF], or epoetin alfa)
• Prior autologous or allogeneic hematopoietic stem cell transplantation (HSCT) allowed
• More than 100 days since prior allogeneic HSCT

Chemotherapy

• See Disease Characteristics
• At least 2 weeks since prior chemotherapy (6 weeks for nitrosoureas)

Endocrine therapy

• Concurrent corticosteroids allowed provided there has been no increase in the dose 1 week prior to and after study entry

  • Steroid taper allowed

Radiotherapy

• At least 3 weeks since prior radiotherapy

  • Allowed in the past 3 weeks provided the volume of the bone marrow treated is < 10% AND the patients has measurable disease outside of the radiation port

Surgery

• Not specified

Other

• Recovered from prior therapy
• At least 30 days since prior investigational drugs
• No other concurrent investigational drugs