BL22 Immunotoxin In Treating Young Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia or Non-Hodgkin's Lymphoma

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Pediatric Phase I Trial of BL22 for Refractory CD22-Positive Leukemias and Lymphomas

Conditions
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Leukemia, Lymphoma

Intervention / Treatment
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* Drug: BL22 immunotoxin
* Procedure: antibody-drug conjugate therapy
* Procedure: immunotoxin therapy
* Procedure: monoclonal antibody therapy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 24 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>BL22 immunotoxin | Drug: BL22 immunotoxin<br>* 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.<br>|
| Active Comparator: 2<br>antibody therapy | Procedure: antibody-drug conjugate therapy<br>* CD22 antibody, RFB4 on day 7<br>|
| Active Comparator: 3<br>immunotoxin therapy | Procedure: immunotoxin therapy<br>* tested for immunogenicity to CAT-8015 before each cycle and at end of study.<br>|
| Active Comparator: 4<br>monoclonal antibody therapy | Procedure: monoclonal antibody therapy<br>* administered intravenously over 30 minutes.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| assessment of efficacy, safety, pharmacokinetics, immunogenicity. |  | end of study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Expansion of MTD |  | end of study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent childhood acute lymphoblastic leukemia, Burkitt lymphoma, recurrent childhood large cell lymphoma, recurrent childhood lymphoblastic lymphoma, childhood non-Hodgkin lymphoma