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:
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
  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:


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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Investigators
Study Chair: Lee Ratner, MD, PhD Washington University Siteman Cancer Center
  More Information

Additional Information:
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, T-Cell
Leukemia, Lymphoid
Leukemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Interferon-alpha
Interferons
Zidovudine
Lamivudine
Cyclophosphamide
Lenograstim
Liposomal doxorubicin
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 August 28, 2014