Combination Chemotherapy Followed By Antiviral Therapy and Interferon Alfa in Treating Patients With HTLV-1-Related Adult T-Cell Leukemia/Lymphoma

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Antiviral therapy may kill viruses such as HTLV-1 that can cause cancer. Interferon alfa may interfere with the growth of cancer cells. Combining chemotherapy with antiviral drugs and interferon alfa may be effective in treating adult T-cell leukemia/lymphoma. PURPOSE: Phase II trial to determine the effectiveness of combination chemotherapy followed by antiviral therapy and interferon alfa in treating patients who have adult T-cell leukemia/lymphoma caused by HTLV-1.

Detailed Description
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OBJECTIVES: Determine the efficacy of etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (EPOCH) followed by lamivudine, zidovudine, and interferon alfa, in terms of response rate, in patients with HTLV-1-associated adult T-cell leukemia/lymphoma. Determine the duration of response in patients treated with this regimen. Determine the toxicity of this regimen in these patients. Determine the effect of this regimen on markers of virus replication and expression and immune function in these patients. OUTLINE: This is a multicenter study. Patients receive EPOCH chemotherapy comprising etoposide, vincristine, and doxorubicin IV continuously on days 1-5, cyclophosphamide IV over 30 minutes on day 5, and oral prednisone on days 1-5. Patients also receive filgrastim (G-CSF) subcutaneously (SC) daily beginning on day 7 and continuing until blood counts recover. Treatment repeats every 21-28 days for at least 2 courses beyond best response or for up to 6 courses in the absence of unacceptable toxicity, disease progression, or stable disease. Beginning 1 month after completion of EPOCH, patients receive oral lamivudine and zidovudine twice daily and interferon alfa SC daily continuously for 1 year. Patients are followed monthly for 1 year, every 2 months for 1 year, and then every 6 months for 3 years. PROJECTED ACCRUAL: A total of 10-32 patients will be accrued for this study within 1-2 years.

Official Title
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Phase II Trial Of Induction Therapy With EPOCH Chemotherapy And Maintenance Therapy With Combivir/Interferon ALPHA-2a For HTLV-1 Associated T-Cell Non-Hodgkin's Lymphoma

Conditions
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Lymphoma

Intervention / Treatment
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* Biological: filgrastim
* Biological: recombinant interferon alfa
* Drug: Etoposide
* Drug: cyclophosphamide
* Drug: doxorubicin hydrochloride
* Drug: lamivudine
* Drug: prednisone
* Drug: vincristine sulfate
* Drug: zidovudine


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed HTLV-1-associated adult T-cell leukemia/lymphoma (ATLL) Previously treated ATLL allowed CD3-positive Documented HTLV-1 infection by serologic assay (ELISA, Western blot) Measurable or evaluable disease PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 50-100% Life expectancy: Not specified Hematopoietic: Absolute neutrophil count greater than 1,000/mm^3* Platelet count greater than 75,000/mm^3* NOTE: *Unless cytopenia is secondary to ATLL Hepatic: Transaminase less than 7 times upper limit of normal Bilirubin less than 2.0 mg/dL (unless secondary to hepatic infiltration with lymphoma or isolated indirect hyperbilirubinemia associated with indinavir) Renal: Creatinine less than 2.0 mg/dL (unless due to lymphoma) Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 6 months after study completion No active opportunistic infection requiring acute therapy No untreated thyroid disease No autoimmune disease No uncontrolled significant psychiatric disease No other concurrent malignancy except carcinoma in situ of the cervix or non-metastatic nonmelanoma skin cancer PRIOR CONCURRENT THERAPY: Biologic therapy: At least 24 hours since prior hematologic growth factors Chemotherapy: Not specified Endocrine therapy: Not specified Radiotherapy: Not specified Surgery: Not specified Other: Concurrent chronic therapy with potentially myelosuppressive agents allowed Other concurrent antiretroviral therapy for HIV, hepatitis B, or hepatitis C infection (or other indication) allowed at investigator's discretion for patients receiving therapy prior to study initiation

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

| Intervention/Treatment |
| --- |
|Biological: filgrastim|5 ug/kg/d|
|Biological: recombinant interferon alfa|9 mU subcutaneously per day for one year|
|Drug: Etoposide|50 mg/m2/day continuous 96 hr infusion, days 1-4|
|Drug: cyclophosphamide|750 mg/m2 IV on day 5|
|Drug: doxorubicin hydrochloride|10 mg/m2/day as a continuous 96-hour infusion days 1-4|
|Drug: lamivudine|150 mg bid|
|Drug: prednisone|60 mg/m2 given orally days 1-5|
|Drug: vincristine sulfate|0.4 mg/m2/day as a 96-hour continuous infusion days 1-4|
|Drug: zidovudine|300 mg bid|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy |  | 60 days | 
| Duration of response |  | 3 years | 
| Effects on markers of virus replication and expression and immune function |  | 5 years | 
| Toxicity |  | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage I adult T-cell leukemia/lymphoma, stage II adult T-cell leukemia/lymphoma, stage III adult T-cell leukemia/lymphoma, stage IV adult T-cell leukemia/lymphoma