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

Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00041327
• Other study ID #: AMC-033
• Secondary ID: U01CA070019CDR00
• Status: Completed
• Phase: Phase 2
• First received: July 8, 2002
• Last updated: February 1, 2016
• Start date: October 2002
• Est. completion date: December 2006

Study information

• Verified date: February 2016
• Source: AIDS Malignancy Consortium
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: December 2006
• Est. primary completion date: December 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 120 Years

Eligibility

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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia, T-Cell
• Leukemia-Lymphoma, Adult T-Cell
• Lymphoma

Intervention

Biological:
• filgrastim
5 ug/kg/d
• recombinant interferon alfa
9 mU subcutaneously per day for one year

Drug:
• Etoposide
50 mg/m2/day continuous 96 hr infusion, days 1-4
• cyclophosphamide
750 mg/m2 IV on day 5
• doxorubicin hydrochloride
10 mg/m2/day as a continuous 96-hour infusion days 1-4
• lamivudine
150 mg bid
• prednisone
60 mg/m2 given orally days 1-5
• vincristine sulfate
0.4 mg/m2/day as a 96-hour continuous infusion days 1-4
• zidovudine
300 mg bid

Locations

Country	Name	City	State
United States	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	Saint Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
AIDS Malignancy Consortium	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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): — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy		60 days	No
Primary	Duration of response		3 years	No
Primary	Effects on markers of virus replication and expression and immune function		5 years	No
Primary	Toxicity		1 year	Yes