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

This study has been completed.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
AIDS Malignancy Clinical Trials Consortium
ClinicalTrials.gov Identifier:
NCT00041327
First received: July 8, 2002
Last updated: November 2, 2011
Last verified: November 2011
History of Changes
  Purpose

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 Intervention Phase
Lymphoma
 Biological: filgrastim
Biological: recombinant interferon alfa
Drug: Etoposide
Drug: cyclophosphamide
Drug: doxorubicin hydrochloride
Drug: lamivudine
Drug: prednisone
Drug: vincristine sulfate
Drug: zidovudine
 Phase 2

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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by AIDS Malignancy Clinical Trials Consortium:

Primary Outcome Measures:
  • Efficacy [ Time Frame: 60 days ] [ Designated as safety issue: No ]
  • Duration of response [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Effects on markers of virus replication and expression and immune function [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Toxicity [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Enrollment: 19
Study Start Date: October 2002
Study Completion Date: December 2006
Primary Completion Date: December 2006 (Final data collection date for primary outcome measure)
Intervention Details:
    Biological: filgrastim
    5 ug/kg/d
    Other Name: Neupogen
    Biological: recombinant interferon alfa
    9 mU subcutaneously per day for one year
    Drug: Etoposide
    50 mg/m2/day continuous 96 hr infusion, days 1-4
    Other Name: VP-16
    Drug: cyclophosphamide
    750 mg/m2 IV on day 5
    Other Name: cytoxan
    Drug: doxorubicin hydrochloride
    10 mg/m2/day as a continuous 96-hour infusion days 1-4
    Other Name: adriamycin
    Drug: lamivudine
    150 mg bid
    Other Name: epivir
    Drug: prednisone
    60 mg/m2 given orally days 1-5
    Other Name: deltasone
    Drug: vincristine sulfate
    0.4 mg/m2/day as a 96-hour continuous infusion days 1-4
    Other Name: Oncovin
    Drug: zidovudine
    300 mg bid
    Other Name: AZT
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00041327

Locations
United States, California
USC/Norris Comprehensive Cancer Center and Hospital
Los Angeles, California, United States, 90089-9181
United States, Florida
University of Miami Sylvester Comprehensive Cancer Center
Miami, Florida, United States, 33136
United States, Missouri
Siteman Cancer Center at Barnes-Jewish Hospital
Saint Louis, Missouri, United States, 63110
Sponsors and Collaborators
AIDS Malignancy Clinical Trials Consortium
National Cancer Institute (NCI)
Investigators
Study Chair: Lee Ratner, MD, PhD Washington University Siteman Cancer Center
  More Information

Additional Information:
Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

Publications:

Responsible Party: AIDS Malignancy Clinical Trials Consortium
ClinicalTrials.gov Identifier: NCT00041327     History of Changes
Other Study ID Numbers: CDR0000069469, U01CA070019, AMC-033
Study First Received: July 8, 2002
Last Updated: November 2, 2011
Health Authority: United States: Federal Government

Keywords provided by AIDS Malignancy Clinical Trials Consortium:
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

Additional relevant MeSH terms:
Leukemia, T-Cell
Leukemia-Lymphoma, Adult T-Cell
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, T-Cell
Leukemia, Lymphoid
Leukemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Interferon-alpha
Interferon Alfa-2a
 Interferons
Zidovudine
Lamivudine
Cyclophosphamide
Lenograstim
Doxorubicin
Etoposide
Prednisone
Vincristine
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 19, 2013