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

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Primary Purpose

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

filgrastim

recombinant interferon alfa

Etoposide

cyclophosphamide

doxorubicin hydrochloride

lamivudine

prednisone

vincristine sulfate

zidovudine

About this trial

This is an interventional treatment trial for Lymphoma focused on measuring 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

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

USC/Norris Comprehensive Cancer Center and Hospital
University of Miami Sylvester Comprehensive Cancer Center
Siteman Cancer Center at Barnes-Jewish Hospital

Outcomes

Primary Outcome Measures

Efficacy

Duration of response

Effects on markers of virus replication and expression and immune function

Toxicity

Secondary Outcome Measures

Full Information

NCT ID

NCT00041327

First Posted

July 8, 2002

Last Updated

February 1, 2016

Sponsor

AIDS Malignancy Consortium

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT00041327

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

February 2016

Overall Recruitment Status

Completed

Study Start Date

October 2002 (undefined)

Primary Completion Date

December 2006 (Actual)

Study Completion Date

December 2006 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

AIDS Malignancy Consortium

Collaborators

National Cancer Institute (NCI)

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Lymphoma

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

19 (Actual)

8. Arms, Groups, and Interventions

Intervention Type

Biological

Intervention Name(s)

filgrastim

Other Intervention Name(s)

Neupogen

Intervention Description

5 ug/kg/d

Intervention Type

Biological

Intervention Name(s)

recombinant interferon alfa

Intervention Description

9 mU subcutaneously per day for one year

Intervention Type

Drug

Intervention Name(s)

Etoposide

Other Intervention Name(s)

VP-16

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

cyclophosphamide

Other Intervention Name(s)

cytoxan

Intervention Description

750 mg/m2 IV on day 5

Intervention Type

Drug

Intervention Name(s)

doxorubicin hydrochloride

Other Intervention Name(s)

adriamycin

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

lamivudine

Other Intervention Name(s)

epivir

Intervention Description

150 mg bid

Intervention Type

Drug

Intervention Name(s)

prednisone

Other Intervention Name(s)

deltasone

Intervention Description

60 mg/m2 given orally days 1-5

Intervention Type

Drug

Intervention Name(s)

vincristine sulfate

Other Intervention Name(s)

Oncovin

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

zidovudine

Other Intervention Name(s)

AZT

Intervention Description

300 mg bid

Primary Outcome Measure Information:

Title

Efficacy

Time Frame

60 days

Title

Duration of response

Time Frame

3 years

Title

Effects on markers of virus replication and expression and immune function

Time Frame

5 years

Title

Toxicity

Time Frame

1 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

120 Years

Accepts Healthy Volunteers

No

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Lee Ratner, MD, PhD

Organizational Affiliation

Washington University Siteman Cancer Center

Official's Role

Study Chair

Facility Information:

Facility Name

USC/Norris Comprehensive Cancer Center and Hospital

City

Los Angeles

State/Province

California

ZIP/Postal Code

90089-9181

Country

United States

Facility Name

University of Miami Sylvester Comprehensive Cancer Center

City

Miami

State/Province

Florida

ZIP/Postal Code

33136

Country

United States

Facility Name

Siteman Cancer Center at Barnes-Jewish Hospital

City

Saint Louis

State/Province

Missouri

ZIP/Postal Code

63110

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

19204798

Citation

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.

Results Reference

result

Lymphoma

About this trial

Eligibility Criteria

Sites / Locations

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial