BL22 Immunotoxin In Treating Young Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia or Non-Hodgkin's Lymphoma
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About
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.
Full description
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.
Enrollment
Sex
Ages
Volunteers
Inclusion and exclusion criteria
DISEASE CHARACTERISTICS:
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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
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Relapsed or refractory disease after at least 1 standard chemotherapy and 1 salvage regimen
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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
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Measurable or evaluable disease
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Prior CNS involvement allowed provided there is no current evidence of CNS malignancy
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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
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No isolated testicular ALL
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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
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Concurrent corticosteroids allowed provided there has been no increase in the dose 1 week prior to and after study entry
- Steroid taper allowed
Radiotherapy
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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
Trial design
Primary purpose
Allocation
Interventional model
Masking
95 participants in 4 patient groups
Trial contacts and locations
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Data sourced from clinicaltrials.gov
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