RFT5-dgA Immunotoxin in Treating Patients With Relapsed or Refractory Cutaneous T-Cell Non-Hodgkin Lymphoma

Study Overview
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Brief Summary
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RATIONALE: Immunotoxins, such as RFT5-dgA immunotoxin (also called anti-CD25 immunotoxin IMTOX25), can find certain cancer cells and kill them without harming normal cells. PURPOSE: This phase II trial is studying the side effects of anti-CD25 immunotoxin IMTOX25 and how well it works in treating patients with relapsed or refractory cutaneous T-cell non-Hodgkin lymphoma.

Detailed Description
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OBJECTIVES: Primary Determine the response rate of patients with relapsed or refractory cutaneous T-cell non-Hodgkin lymphoma (CTCL) following treatment with RFT5-dgA immunotoxin (anti-CD25 immunotoxin IMTOX25) . Secondary Determine whether responses correlate with the level of CD25+ expression on the CTCL tumor cells. Determine whether changes in the pre-treatment and the post-treatment levels of CD4+CD25+ Treg cells correlate with responses. OUTLINE: Patients receive anti-CD25 immunotoxin IMTOX25 IV over 4 hours on days 1, 3, and 5. Treatment repeats every 6 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Tissue and blood samples are collected at baseline, and during study for CD25+ expression by fluorescent-activated cell sorter analysis, immunohistochemistry. After completion of study therapy, patients are followed every 3 months for 2 years, every 6 months for 2 years, and then annually thereafter.

Official Title
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Phase II Study of IMTOX25 in Relapsed/Refractory Cutaneous T-Cell Lymphoma

Conditions
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Lymphoma

Intervention / Treatment
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* Biological: RFT5-dgA immunotoxin
* Other: fluorescence activated cell sorting
* Other: immunohistochemistry staining method


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed cutaneous T-cell non-Hodgkin lymphoma (CTCL) Relapsed or refractory disease, meeting 1 of the following criteria: Progression of disease following 2 prior chemotherapies Failure to respond to the second prior chemotherapy Measurable disease PATIENT CHARACTERISTICS: ECOG performance status 0-2 Life expectancy > 3 months Serum creatinine < 1.5 times upper limit of normal (ULN) Serum AST/ALT < 2.5 times ULN Total bilirubin ≤ 2.0 mg/dL (< 3.0 mg/dL in patients with Gilbert syndrome) WBC count ≥ 3,000/mm³ Platelet count ≥ 100,000/mm³ Serum albumin > 2.5 g/dL LVEF ≥ 45% by 2-D ECHO or MUGA scan Human antimurine antibody < 1 μg/mL Patients with a history of electrocardiogram abnormalities, symptoms of cardiac ischemia, or arrhythmias must have a normal cardiac stress test (i.e., stress thallium, stress MUGA, dobutamine echocardiogram, or other stress test) Must be willing to undergo venipuncture and central line placement Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No HBV surface antigen, HCV, or HIV antibody positivity No autoimmune disease or immunodeficiency (i.e., HIV) No history of uncontrolled concurrent illness including, but not limited to, any of the following: Ongoing or active infection Ongoing or active cardiac disease (i.e., congestive heart failure, unstable angina pectoris, or cardiac arrhythmia) Psychiatric illness and/or social situation that would preclude study compliance No other malignancies except treated basal cell or squamous cell carcinoma of the skin, or treated carcinoma in situ of the cervix PRIOR CONCURRENT THERAPY: See Disease Characteristics More than 3 weeks since prior systemic therapy for CTCL More than 6 months since prior chronic steroid therapy or chronic anti-coagulation therapy No prior therapy with anti-CD25 immunotoxin IMTOX25 and/or Ontak No other concurrent cancer chemotherapy, experimental therapy, investigational agent, or immunomodulating agent (including steroids)

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IMTOX25 at 2mg/m²/dose<br>Patients will receive IMTOX25 at 2mg/m²/dose, by IV administration, every other day for a total of 3 doses. A total of 6 cycles of treatment will be allowed. A cycle is equal to 6 weeks, with IMTOX25 infusion on Day 1, 3 and 5, followed by a 5 week rest period. | Biological: RFT5-dgA immunotoxin<br> <br> Other: fluorescence activated cell sorting<br> <br> Other: immunohistochemistry staining method<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate - Cutaneous T Cell Lymphoma (CTCL) | Response rate of patients with relapsed/refractory Cutaneous T Cell Lymphoma (CTCL) following treatment with IMTOX25. | Once a week for seven weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent mycosis fungoides/Sezary syndrome, recurrent cutaneous T-cell non-Hodgkin lymphoma