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.

Condition	Treatment or Intervention	Phase
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	Drug: cyclophosphamide  Drug: doxorubicin  Drug: etoposide  Drug: filgrastim  Drug: interferon alfa  Drug: lamivudine  Drug: prednisone  Drug: vincristine  Drug: zidovudine  Procedure: antiviral therapy  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: colony-stimulating factor therapy  Procedure: cytokine therapy  Procedure: interferon therapy	Phase II

Further Study Details: 

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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

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

California
      USC/Norris Comprehensive Cancer Center and Hospital, Los Angeles,  California,  90033-0804,  United States; Recruiting
Florida
      University of Miami Sylvester Comprehensive Cancer Center, Miami,  Florida,  33136,  United States; Recruiting
Missouri
      Siteman Cancer Center at Barnes-Jewish Hospital, Saint Louis,  Missouri,  63110,  United States; Recruiting

Study chairs or principal investigators

Lee Ratner, MD, PhD,  Study Chair,  Barnes-Jewish Hospital   

Study ID Numbers:  CDR0000069469; AMC-033; NCT00041327
Record last reviewed:  June 2003
Last Updated:  December 3, 2004
Record first received:  July 8, 2002
ClinicalTrials.gov Identifier:  NCT00041327
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08