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

NCT ID: NCT00041327

Last Updated: 2016-02-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-10-31
• Study Completion Date: 2006-12-31

Brief Summary

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

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.

Conditions

Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

filgrastim

5 ug/kg/d

Intervention Type: BIOLOGICAL

recombinant interferon alfa

9 mU subcutaneously per day for one year

Intervention Type: BIOLOGICAL

Etoposide

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

Intervention Type: DRUG

cyclophosphamide

750 mg/m2 IV on day 5

Intervention Type: DRUG

doxorubicin hydrochloride

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

Intervention Type: DRUG

lamivudine

150 mg bid

Intervention Type: DRUG

prednisone

60 mg/m2 given orally days 1-5

Intervention Type: DRUG

vincristine sulfate

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

Intervention Type: DRUG

zidovudine

300 mg bid

Intervention Type: DRUG

Other Intervention Names

Neupogen; VP-16; cytoxan; adriamycin; epivir; deltasone; Oncovin; AZT

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

AIDS Malignancy Consortium

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lee Ratner, MD, PhD

Role: STUDY_CHAIR

Washington University Siteman Cancer Center

Locations

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

Countries

United States

References

Ratner L, Harrington W, Feng X, Grant C, Jacobson S, Noy A, Sparano J, Lee J, Ambinder R, Campbell N, Lairmore M; AIDS Malignancy Consortium. Human T cell leukemia virus reactivation with progression of adult T-cell leukemia-lymphoma. PLoS One. 2009;4(2):e4420. doi: 10.1371/journal.pone.0004420. Epub 2009 Feb 10.

Reference Type: RESULT

PMID: 19204798 (View on PubMed)

Other Identifiers

U01CA070019

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CDR0000069469

Identifier Type: OTHER

Identifier Source: secondary_id

AMC-033

Identifier Type: -

Identifier Source: org_study_id