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

AIDS Malignancy Consortium

Status and phase

Completed

Phase 2

Conditions

Lymphoma

Treatments

Drug: doxorubicin hydrochloride

Drug: zidovudine

Biological: recombinant interferon alfa

Drug: cyclophosphamide

Drug: lamivudine

Drug: vincristine sulfate

Drug: prednisone

Drug: Etoposide

Biological: filgrastim

Study type

Interventional

Funder types

NETWORK

NIH

Identifiers

NCT00041327

AMC-033

U01CA070019 (U.S. NIH Grant/Contract)

CDR0000069469 (Other Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment

19 patients

Sex

All

Ages

18 to 120 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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