Fludarabine and Cyclophosphamide Followed By LMB-2 Immunotoxin in Treating Patients With Hodgkin's Lymphoma

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as fludarabine and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. LMB-2 immunotoxin can find cancer cells and kill them without harming normal cells. Giving fludarabine and cyclophosphamide followed by LMB-2 immunotoxin may kill more cancer cells. PURPOSE: This clinical trial is studying how well giving fludarabine and cyclophosphamide followed by LMB-2 immunotoxin works in treating patients with Hodgkin's lymphoma.

Detailed Description
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OBJECTIVES: Primary Determine the feasibility of pretreatment with fludarabine phosphate and cyclophosphamide in preventing neutralization of antibodies in patients with CD25-positive Hodgkin's lymphoma. Secondary Determine the response rate in patients treated with LMB-2 immunotoxin. Determine the response duration in patients receiving this treatment. Correlate serum levels of LMB-2 immunotoxin with toxicity and response in these patients. Assess the development of neutralizing antibodies and the effect of these antibodies on blood levels of LMB-2 immunotoxin and toxicity. Correlate soluble Tac-peptide levels with treatment response in these patients. OUTLINE: This is a nonrandomized, pilot study. Patients receive fludarabine phosphate IV over 30 minutes and cyclophosphamide IV over 60 minutes on days 1-4 and filgrastim (G-CSF) subcutaneously once daily beginning on day 5 and continuing until blood counts recover. Beginning 4 weeks after completion of chemotherapy, patients receive LMB-2 immunotoxin IV over 30 minutes on days 1, 3, and 5. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression. Blood is obtained prior to and after chemotherapy and then periodically during LMB-2 immunotoxin therapy for pharmacokinetic studies to measure lymphocyte subsets. PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

Official Title
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A Pilot Study of Anti-Tac(Fv)-PE38 (LMB-2) Immunotoxin for Treatment of CD25 Positive Hodgkin's Disease After Fludarabine and Cyclophosphamide

Conditions
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Lymphoma

Intervention / Treatment
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* Biological: LMB-2 immunotoxin
* Drug: cyclophosphamide
* Drug: fludarabine phosphate
* Other: pharmacological study


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histopathologically confirmed CD25+ Hodgkin's lymphoma At least 20% of the malignant cells positive by immunohistochemistry Stage II-IV disease Meets the following criteria: Failed standard chemotherapy Not eligible for curative salvage radiotherapy or chemotherapy Not eligible for or refused bone marrow transplantation Measurable disease No patient whose serum neutralizes LMB-2 immunotoxin in tissue culture, due either to antitoxin or antimouse-IgG antibodies No patient whose serum neutralizes > 75% of the activity of 1 µg/mL of LMB-2 immunotoxin PATIENT CHARACTERISTICS: ECOG performance status 0-2 Absolute neutrophil count ≥ 1,000/mm³ Platelet count ≥ 50,000/mm³ Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception ALT and AST ≤ 2.5 times upper limit of normal Albumin ≥ 3.0 g/dL Bilirubin ≤ 2.2 mg/dL (< 5 mg/dL if Gilbert's syndrome is present) Creatinine ≤ 1.4 mg/dL OR creatinine clearance ≥ 50 mL/min No uncontrolled intercurrent illness including, but not limited to, any of the following: Ongoing or active infection Symptomatic congestive heart failure Unstable angina pectoris Cardiac arrhythmia Psychiatric illness or social situations that would limit study compliance No HIV or hepatitis C positivity Hepatitis B surface antigen positivity allowed provided patient is receiving lamivudine LVEF ≥ 45% DLCO ≥ 50% of normal OR FEV_1 ≥ 60% of normal No active second malignancy requiring treatment PRIOR CONCURRENT THERAPY: See Disease Characteristics No systemic cytotoxic chemotherapy within the past 4 weeks No systemic steroids (except stable doses of prednisone ≤ 20 mg/day) within the past 4 weeks No monoclonal antibody therapy within the past 12 weeks No prior LMB-2 immunotoxin No concurrent warfarin

Ages Eligible for Study
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Minimum Age: 18 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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: LMB-2 immunotoxin|nan|
|Drug: cyclophosphamide|nan|
|Drug: fludarabine phosphate|nan|
|Other: pharmacological study|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of using fludarabine phosphate and cyclophosphamide to decrease neutralizing antibodies |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate |  |  | 
| Response duration |  |  | 
| Correlation of serum levels of LMB-2 immunotoxin with toxicity and response |  |  | 
| Development of neutralizing antibodies and its effect on blood level of LMB-2 immunotoxin and toxicity |  |  | 
| Correlation of soluble Tac-peptide with treatment response |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage II adult Hodgkin lymphoma, stage III adult Hodgkin lymphoma, stage IV adult Hodgkin lymphoma, recurrent adult Hodgkin lymphoma