Anti-CD19 and Anti-CD22 Immunotoxins in Treating Patients With Refractory or Relapsed B-Cell Acute Lymphoblastic Leukemia

Study Overview
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Brief Summary
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RATIONALE: Immunotoxins, such as anti-CD19 and anti-CD22, can find cancer cells that express CD19 and CD22 and kill them without harming normal cells. This may be an effective treatment for B-cell acute lymphoblastic leukemia. PURPOSE: This phase I trial is studying the side effects and best dose of anti-CD19 and anti-CD22 immunotoxins in treating patients with refractory or relapsed B-cell acute lymphoblastic leukemia.

Detailed Description
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OBJECTIVES: Determine the maximum tolerated dose of deglycosylated ricin A chain-conjugated anti-CD19 and anti-CD22 immunotoxins (Combotox) in patients with refractory or relapsed B-cell acute lymphoblastic leukemia. Determine the toxicity of Combotox in these patients. Determine the pharmacokinetic (PK) profile of Combotox in these patients. Determine any antitumor activity of Combotox, in terms of the percentage of blasts in bone marrow and peripheral blood. Determine the levels of human antimouse and human anti-dgA antibodies in patients treated with Combotox. Determine if there is a correlation between PK parameters and toxicity of Combotox in these patients. Determine if the expression of the CD19 and CD22 cell surface antigens is affected by Combotox. OUTLINE: This is a dose-escalation study. Patients receive deglycosylated ricin A chain-conjugated anti-CD19 and anti-CD22 immunotoxins (Combotox) IV over 4 hours on days 1, 3, and 5 in the absence of disease progression or unacceptable toxicity. Cohorts of patients receive escalating doses of Combotox until the maximum tolerated dose is determined. After completion of study treatment, patients are followed periodically. PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.

Official Title
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A Phase I Study of Combination Therapy With Anti-CD19 and Anti-CD22 Immunotoxins (Combotox) in Adults With Refractory/Relapse Acute Lymphoblastic Leukemia

Conditions
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Leukemia

Intervention / Treatment
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* Biological: deglycosylated ricin A chain-conjugated anti-CD19/anti-CD22 immunotoxins


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed adult acute lymphoblastic leukemia B-cell lineage Refractory or relapsed disease based on a bone marrow/peripheral blood examination, cytogenetic studies, or polymerase chain reaction amplification Disease refractory to conventional therapy and other therapies of higher priority At least 50% of the blasts (in bone marrow or peripheral blood) expressing CD19 and/or CD22 by flow cytometry PATIENT CHARACTERISTICS: ECOG performance status 0-2 Life expectancy > 2 months Creatinine < 1.5 times normal Bilirubin < 1.5 times normal ALT or AST < 2.5 times normal PRIOR CONCURRENT THERAPY: Prior chemotherapy, biologic therapy, and/or radiotherapy allowed

Ages Eligible for Study
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Minimum Age: 17 Years
Maximum Age: 120 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: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Combination Therapy with Immunotoxins Imtox 19 Plus Imtox 22<br> | Biological: deglycosylated ricin A chain-conjugated anti-CD19/anti-CD22 immunotoxins<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Optimum dose of deglycosylated ricin A chain-conjugated anti-CD19 and anti-CD22 immunotoxins (Combotox) |  |  | 
| Efficacy of treatment |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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B-cell adult acute lymphoblastic leukemia, recurrent adult acute lymphoblastic leukemia