SWOG-9239 Reduction of Immunosuppression Plus Interferon Alfa and Combination Chemotherapy in Treating Patients With Malignant Tumors That Develop After Organ Transplant

NCT ID: NCT00002657

Last Updated: 2013-01-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

1995-05-31

Study Completion Date

2011-07-31

Brief Summary

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RATIONALE: Reducing the amount of drugs used to prevent transplant rejection may help a person's body kill tumor cells. Giving biological therapy, such as interferon alfa, which may interfere with the growth of cancer cells, or combination chemotherapy, which uses different ways to stop tumor cells from dividing so they stop growing or die, may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of reducing immunosuppression, and giving interferon alfa and combination chemotherapy, in treating patients who have malignant tumors that develop after organ transplant.

Detailed Description

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OBJECTIVES: I. Evaluate the complete remission rate and survival of patients with lymphoproliferation following organ transplantation treated with a defined sequential approach: modification of immunosuppression, with surgery or limited radiotherapy for an isolated site of disease; interferon alfa; and chemotherapy (ProMACE-CytaBOM; cyclophosphamide, doxorubicin, etoposide, prednisone, cytarabine, bleomycin, vincristine, methotrexate).

OUTLINE: All patients receive modification of immunocompetence, unless rejection is present at outset. These patients proceed directly to interferon treatment. Group 1 (see Disease Characteristics): Patients receive reduced doses of their current immunosuppressive therapy for 10 days. Group 2: Patients receive reduced doses of some of their current immunosuppressive therapy and discontinue some of the other therapy for 14 days. Immunosuppressive therapy then resumes on day 15. Immunosuppressive therapy continues throughout other therapy, unless otherwise noted. Some patients may then undergo surgery or radiotherapy. Interferon therapy: Patients receive interferon alfa (IFNA) subcutaneously or intramuscularly on days 1-28 for a maximum of 3 courses. Patients then receive maintenance therapy with IFNA 3 days a week for 4 weeks for up to 6 courses. Chemotherapy (ProMACE-CytaBOM): Immunosuppressive therapy is stopped on days 1-20. Patients receive cyclophosphamide IV, doxorubicin IV, and etoposide IV over 60 minutes on day 1, oral prednisone on days 1-14, and cytarabine IV, bleomycin IV, vincristine IV, and methotrexate IV on day 8. Treatment is repeated every 21 days for up to 6 courses. Patients with positive CSF cytology receive intrathecal methotrexate or cytarabine on days 1, 3, 5, 7, and 14. Some patients may continue this therapy on day 21 , then every 3 weeks for 5 doses, or may receive cranial irradiation. Patients are followed monthly for 1 year, every 2 months for 1 year, every 4 months for 1 year, then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study within 4-5 years.

Conditions

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Lymphoma Multiple Myeloma and Plasma Cell Neoplasm

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Immumosuppression, IFN-a, ProMACE-CytaBOM

Doses and schedules of immunosuppressive drugs (cyclosporin (or FK506), prednisone, and acyclovir) will depend on whether patients are judged to have clinically urgent disease or not. Patients who do not have a CR after initial immunosuppression will receive 3 cycles (28 days each) Interferon alpha 2b at 3.0 x 10\^6 IU/m\^2 on days 1-28. Patients who have a CR will then receive 6 additional cycles with 3 doses per week, then go onto observation. Patients who do not have a CR will then receive a maximum of 6 21-day cycles of chemotherapy, consisting of: cyclophosphamide 650 mg/m\^2 on day 1, adriamycin 25 mg/m\^2 on day 1, etoposide 120 mg/m\^2 on day 1, prednisone 60 mg/m\^2 on days 1-14, cytosine arabinoside 300 mg/m\^2 on day 8, bleomycin 5 mg/m\^2 on day 8, vincristine 1.4 mg/m\^2 on day 8, methotrexate 120 mg/m\^2 on day 8, leucovorin 25 mg/m\^2 q 6 hours on days 8-9, G-CSF 5 ug/kg/day on days 2-14, and one double strength tablet trimethoprim-sulfamethoxazole 3 times per week.

Group Type EXPERIMENTAL

bleomycin sulfate

Intervention Type BIOLOGICAL

5 mg/m\^2

recombinant interferon alfa

Intervention Type BIOLOGICAL

3.0 x 10\^6 IU/m\^2

cyclophosphamide

Intervention Type DRUG

650 mg/m\^2

cytarabine

Intervention Type DRUG

300 mg/m\^2

doxorubicin hydrochloride

Intervention Type DRUG

25 mg/m\^2

etoposide

Intervention Type DRUG

120 mg/m\^2

methotrexate

Intervention Type DRUG

120 mg/m\^2

prednisone

Intervention Type DRUG

dose varies during initial immunosuppression. During chemotherapy, 60 mg/m\^2.

vincristine sulfate

Intervention Type DRUG

1.4 mg/m\^2

conventional surgery

Intervention Type PROCEDURE

Simple excision, for those patients who have resectable disease after initial immunosuppression.

radiation therapy

Intervention Type RADIATION

For treatment of localized disease that remains after initial immunosuppression.

Interventions

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bleomycin sulfate

5 mg/m\^2

Intervention Type BIOLOGICAL

recombinant interferon alfa

3.0 x 10\^6 IU/m\^2

Intervention Type BIOLOGICAL

cyclophosphamide

650 mg/m\^2

Intervention Type DRUG

cytarabine

300 mg/m\^2

Intervention Type DRUG

doxorubicin hydrochloride

25 mg/m\^2

Intervention Type DRUG

etoposide

120 mg/m\^2

Intervention Type DRUG

methotrexate

120 mg/m\^2

Intervention Type DRUG

prednisone

dose varies during initial immunosuppression. During chemotherapy, 60 mg/m\^2.

Intervention Type DRUG

vincristine sulfate

1.4 mg/m\^2

Intervention Type DRUG

conventional surgery

Simple excision, for those patients who have resectable disease after initial immunosuppression.

Intervention Type PROCEDURE

radiation therapy

For treatment of localized disease that remains after initial immunosuppression.

Intervention Type RADIATION

Other Intervention Names

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adriamycin

Eligibility Criteria

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Inclusion Criteria

PATIENT CHARACTERISTICS: Age: 15 and over Performance status: Not specified Hematopoietic: Not specified Hepatic: See Disease Characteristics Renal: Not specified Cardiovascular: See Disease Characteristics Pulmonary: See Disease Characteristics Other: No known AIDS, HIV-associated complex, or positive HIV antibody No other malignancy within past 5 years, except: Adequately treated basal or squamous cell skin cancer Adequately treated stage I or II cancer or other noninvasive cancers Carcinoma in situ of the cervix Not pregnant or nursing Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy: No prior interferon for lymphoma No prior bone marrow transplantation Chemotherapy: No prior chemotherapy for lymphoma Endocrine therapy: Not specified Radiotherapy: Not specified Surgery: See Disease Characteristics Other: Intra-aortic balloon pump allowed only for heart failure caused by acute rejection or lymphomatous involvement
Minimum Eligible Age

15 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Eastern Cooperative Oncology Group

NETWORK

Sponsor Role collaborator

SWOG Cancer Research Network

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Lode J. Swinnen, MD

Role: STUDY_CHAIR

Loyola University

Leo I. Gordon, MD

Role: STUDY_CHAIR

Robert H. Lurie Cancer Center

Locations

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MBCCOP - University of South Alabama

Mobile, Alabama, United States

Site Status

CCOP - Greater Phoenix

Phoenix, Arizona, United States

Site Status

Veterans Affairs Medical Center - Phoenix (Hayden)

Phoenix, Arizona, United States

Site Status

Veterans Affairs Medical Center - Tucson

Tucson, Arizona, United States

Site Status

Arizona Cancer Center

Tucson, Arizona, United States

Site Status

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status

Veterans Affairs Medical Center - Little Rock (McClellan)

Little Rock, Arkansas, United States

Site Status

Veterans Affairs Medical Center - Long Beach

Long Beach, California, United States

Site Status

USC/Norris Comprehensive Cancer Center

Los Angeles, California, United States

Site Status

Jonsson Comprehensive Cancer Center, UCLA

Los Angeles, California, United States

Site Status

Beckman Research Institute, City of Hope

Los Angeles, California, United States

Site Status

Veterans Affairs Outpatient Clinic - Martinez

Martinez, California, United States

Site Status

CCOP - Bay Area Tumor Institute

Oakland, California, United States

Site Status

University of California Davis Medical Center

Sacramento, California, United States

Site Status

CCOP - Santa Rosa Memorial Hospital

Santa Rosa, California, United States

Site Status

David Grant Medical Center

Travis Air Force Base, California, United States

Site Status

Veterans Affairs Medical Center - Denver

Denver, Colorado, United States

Site Status

University of Colorado Cancer Center

Denver, Colorado, United States

Site Status

CCOP - Atlanta Regional

Atlanta, Georgia, United States

Site Status

Cancer Research Center of Hawaii

Honolulu, Hawaii, United States

Site Status

CCOP - Central Illinois

Decatur, Illinois, United States

Site Status

Veterans Affairs Medical Center - Hines (Hines Junior VA Hospital)

Hines, Illinois, United States

Site Status

Loyola University Medical Center

Maywood, Illinois, United States

Site Status

University of Kansas Medical Center

Kansas City, Kansas, United States

Site Status

CCOP - Wichita

Wichita, Kansas, United States

Site Status

Veterans Affairs Medical Center - Wichita

Wichita, Kansas, United States

Site Status

Veterans Affairs Medical Center - Lexington

Lexington, Kentucky, United States

Site Status

Albert B. Chandler Medical Center, University of Kentucky

Lexington, Kentucky, United States

Site Status

MBCCOP - LSU Medical Center

New Orleans, Louisiana, United States

Site Status

Tulane University School of Medicine

New Orleans, Louisiana, United States

Site Status

Veterans Affairs Medical Center - New Orleans

New Orleans, Louisiana, United States

Site Status

Louisiana State University Health Sciences Center - Shreveport

Shreveport, Louisiana, United States

Site Status

Veterans Affairs Medical Center - Shreveport

Shreveport, Louisiana, United States

Site Status

Boston Medical Center

Boston, Massachusetts, United States

Site Status

Veterans Affairs Medical Center - Boston (Jamaica Plain)

Jamaica Plain, Massachusetts, United States

Site Status

Veterans Affairs Medical Center - Ann Arbor

Ann Arbor, Michigan, United States

Site Status

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Site Status

Veterans Affairs Medical Center - Detroit

Detroit, Michigan, United States

Site Status

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Henry Ford Hospital

Detroit, Michigan, United States

Site Status

CCOP - Grand Rapids Clinical Oncology Program

Grand Rapids, Michigan, United States

Site Status

Providence Hospital - Southfield

Southfield, Michigan, United States

Site Status

CCOP - Metro-Minnesota

Saint Louis Park, Minnesota, United States

Site Status

Veterans Affairs Medical Center - Biloxi

Biloxi, Mississippi, United States

Site Status

University of Mississippi Medical Center

Jackson, Mississippi, United States

Site Status

Veterans Affairs Medical Center - Jackson

Jackson, Mississippi, United States

Site Status

Keesler Medical Center - Keesler AFB

Keesler Air Force Base, Mississippi, United States

Site Status

Veterans Affairs Medical Center - Kansas City

Kansas City, Missouri, United States

Site Status

CCOP - Kansas City

Kansas City, Missouri, United States

Site Status

CCOP - Cancer Research for the Ozarks

Springfield, Missouri, United States

Site Status

St. Louis University Health Sciences Center

St Louis, Missouri, United States

Site Status

CCOP - St. Louis-Cape Girardeau

St Louis, Missouri, United States

Site Status

CCOP - Montana Cancer Consortium

Billings, Montana, United States

Site Status

Veterans Affairs Medical Center - Albuquerque

Albuquerque, New Mexico, United States

Site Status

MBCCOP - University of New Mexico HSC

Albuquerque, New Mexico, United States

Site Status

Veterans Affairs Medical Center - Brooklyn

Brooklyn, New York, United States

Site Status

Herbert Irving Comprehensive Cancer Center

New York, New York, United States

Site Status

Barrett Cancer Center, The University Hospital

Cincinnati, Ohio, United States

Site Status

Veterans Affairs Medical Center - Cincinnati

Cincinnati, Ohio, United States

Site Status

Cleveland Clinic Cancer Center

Cleveland, Ohio, United States

Site Status

CCOP - Columbus

Columbus, Ohio, United States

Site Status

Veterans Affairs Medical Center - Dayton

Dayton, Ohio, United States

Site Status

CCOP - Dayton

Kettering, Ohio, United States

Site Status

Oklahoma Medical Research Foundation

Oklahoma City, Oklahoma, United States

Site Status

Veterans Affairs Medical Center - Oklahoma City

Oklahoma City, Oklahoma, United States

Site Status

Oregon Cancer Center at Oregon Health Sciences University

Portland, Oregon, United States

Site Status

Veterans Affairs Medical Center - Portland

Portland, Oregon, United States

Site Status

CCOP - Columbia River Program

Portland, Oregon, United States

Site Status

CCOP - Greenville

Greenville, South Carolina, United States

Site Status

CCOP - Upstate Carolina

Spartanburg, South Carolina, United States

Site Status

Veterans Affairs Medical Center - Nashville

Nashville, Tennessee, United States

Site Status

Vanderbilt Cancer Center

Nashville, Tennessee, United States

Site Status

Brooke Army Medical Center

Fort Sam Houston, Texas, United States

Site Status

University of Texas Medical Branch

Galveston, Texas, United States

Site Status

Texas Tech University Health Science Center

Lubbock, Texas, United States

Site Status

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Site Status

Veterans Affairs Medical Center - San Antonio (Murphy)

San Antonio, Texas, United States

Site Status

Veterans Affairs Medical Center - Temple

Temple, Texas, United States

Site Status

CCOP - Scott and White Hospital

Temple, Texas, United States

Site Status

Huntsman Cancer Institute

Salt Lake City, Utah, United States

Site Status

Veterans Affairs Medical Center - Salt Lake City

Salt Lake City, Utah, United States

Site Status

CCOP - Virginia Mason Research Center

Seattle, Washington, United States

Site Status

Swedish Cancer Institute

Seattle, Washington, United States

Site Status

Veterans Affairs Medical Center - Seattle

Seattle, Washington, United States

Site Status

Puget Sound Oncology Consortium

Seattle, Washington, United States

Site Status

CCOP - Northwest

Tacoma, Washington, United States

Site Status

Countries

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United States

References

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Swinnen LJ, LeBlanc M, Grogan TM, Gordon LI, Stiff PJ, Miller AM, Kasamon Y, Miller TP, Fisher RI. Prospective study of sequential reduction in immunosuppression, interferon alpha-2B, and chemotherapy for posttransplantation lymphoproliferative disorder. Transplantation. 2008 Jul 27;86(2):215-22. doi: 10.1097/TP.0b013e3181761659.

Reference Type RESULT
PMID: 18645482 (View on PubMed)

Gulley ML, Swinnen LJ, Plaisance KT Jr, Schnell C, Grogan TM, Schneider BG; Southwest Oncology Group. Tumor origin and CD20 expression in posttransplant lymphoproliferative disorder occurring in solid organ transplant recipients: implications for immune-based therapy. Transplantation. 2003 Sep 27;76(6):959-64. doi: 10.1097/01.TP.0000079832.00991.EE.

Reference Type RESULT
PMID: 14508361 (View on PubMed)

Swinnen LJ, Gulley ML, Hamilton E, et al.: EBV DNA quantitation in serum is highly correlated with the development and regression of post-transplant lymphoproliferative disorder (PTLD) in solid organ transplant recipients. Blood 92(10 suppl 1): A1291, 314-315a, 1998.

Reference Type RESULT

Tao Q, Swinnen L, Ambinder RF: Conservation of Epstein-Barr virus (EBV) CTL epitopes in EVB (+) posttransplant lymphomas in solid organ transplant recipients. Blood 90(10 suppl 1): A2281, 512a, 1997.

Reference Type RESULT

Other Identifiers

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SWOG-9239

Identifier Type: OTHER

Identifier Source: secondary_id

E-S9239

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA032102

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CDR0000064200

Identifier Type: -

Identifier Source: org_study_id

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