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

AIDS Malignancy Consortium19 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

Interventions

filgrastimBIOLOGICAL

5 ug/kg/d

recombinant interferon alfaBIOLOGICAL

9 mU subcutaneously per day for one year

EtoposideDRUG

50 mg/m2/day continuous 96 hr infusion, days 1-4

cyclophosphamideDRUG

750 mg/m2 IV on day 5

doxorubicin hydrochlorideDRUG

10 mg/m2/day as a continuous 96-hour infusion days 1-4

lamivudineDRUG

150 mg bid

prednisoneDRUG

60 mg/m2 given orally days 1-5

vincristine sulfateDRUG

0.4 mg/m2/day as a 96-hour continuous infusion days 1-4

zidovudineDRUG

300 mg bid

Eligibility

Sex: ALLMin age: 18 YearsMax age: 120 Years

Medical Language ↔ Plain English

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

Locations (3)

USC/Norris Comprehensive Cancer Center and Hospital

Los Angeles, California, United States

University of Miami Sylvester Comprehensive Cancer Center

Miami, Florida, United States

Siteman Cancer Center at Barnes-Jewish Hospital

St Louis, Missouri, United States

Outcomes

Primary Outcomes

Efficacy

Time frame: 60 days

Duration of response

Time frame: 3 years

Effects on markers of virus replication and expression and immune function

Time frame: 5 years

Toxicity

Time frame: 1 year