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

Phase II Trial of Sequential Modification of Immunosuppression, Interferon Alpha, and Promace-Cytabom For Treatment of Post-Cardiac Transplant Lymphoproliferation.

Sponsors

Lead Sponsor: Southwest Oncology Group

Collaborator: National Cancer Institute (NCI)
Eastern Cooperative Oncology Group

Source Southwest Oncology Group
Brief Summary

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

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.

Overall Status Completed
Start Date May 1995
Completion Date July 2011
Primary Completion Date November 2003
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Response every 3 months while on protocol treatment
Secondary Outcome
Measure Time Frame
overall survival every 3 months while on treatment, then every 6 months thereafter
Enrollment 20
Condition
Intervention

Intervention Type: Biological

Intervention Name: bleomycin sulfate

Description: 5 mg/m^2

Arm Group Label: Immumosuppression, IFN-a, ProMACE-CytaBOM

Intervention Type: Biological

Intervention Name: recombinant interferon alfa

Description: 3.0 x 10^6 IU/m^2

Arm Group Label: Immumosuppression, IFN-a, ProMACE-CytaBOM

Intervention Type: Drug

Intervention Name: cyclophosphamide

Description: 650 mg/m^2

Arm Group Label: Immumosuppression, IFN-a, ProMACE-CytaBOM

Intervention Type: Drug

Intervention Name: cytarabine

Description: 300 mg/m^2

Arm Group Label: Immumosuppression, IFN-a, ProMACE-CytaBOM

Intervention Type: Drug

Intervention Name: doxorubicin hydrochloride

Description: 25 mg/m^2

Arm Group Label: Immumosuppression, IFN-a, ProMACE-CytaBOM

Other Name: adriamycin

Intervention Type: Drug

Intervention Name: etoposide

Description: 120 mg/m^2

Arm Group Label: Immumosuppression, IFN-a, ProMACE-CytaBOM

Intervention Type: Drug

Intervention Name: methotrexate

Description: 120 mg/m^2

Arm Group Label: Immumosuppression, IFN-a, ProMACE-CytaBOM

Intervention Type: Drug

Intervention Name: prednisone

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

Arm Group Label: Immumosuppression, IFN-a, ProMACE-CytaBOM

Intervention Type: Drug

Intervention Name: vincristine sulfate

Description: 1.4 mg/m^2

Arm Group Label: Immumosuppression, IFN-a, ProMACE-CytaBOM

Intervention Type: Procedure

Intervention Name: conventional surgery

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

Arm Group Label: Immumosuppression, IFN-a, ProMACE-CytaBOM

Intervention Type: Radiation

Intervention Name: radiation therapy

Description: For treatment of localized disease that remains after initial immunosuppression.

Arm Group Label: Immumosuppression, IFN-a, ProMACE-CytaBOM

Eligibility

Criteria:

DISEASE CHARACTERISTICS: Histologically proven lymphoproliferation following organ (kidney, liver, or heart) allograft Bidimensionally measurable disease If all disease removed at biopsy, eligible only if recurrence is bidimensionally measurable Group 1 (clinically urgent disease): Histologically proven involvement of the allograft OR Histologically proven bone marrow involvement OR Liver involvement with hepatic insufficiency Bilirubin greater than upper limit of normal (ULN) OR SGOT or SGPT at least 2 times ULN OR Clinical hepatic encephalopathy OR LDH at least 3 times ULN OR Systemic sepsis OR Locally urgent lesions Tonsillar enlargement that threatens airway Superior vena cava syndrome Bilateral hydronephrosis Postobstructive pneumonia OR Small noncleaved lymphocytic lymphoma (i.e., adult Burkitt's lymphoma) Group 2: All other patients No CNS disease only

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

Gender: All

Minimum Age: 15 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Location
Facility:
MBCCOP - University of South Alabama | Mobile, Alabama, 36688, United States
CCOP - Greater Phoenix | Phoenix, Arizona, 85006-2726, United States
Veterans Affairs Medical Center - Phoenix (Hayden) | Phoenix, Arizona, 85012, United States
Veterans Affairs Medical Center - Tucson | Tucson, Arizona, 85723, United States
Arizona Cancer Center | Tucson, Arizona, 85724, United States
University of Arkansas for Medical Sciences | Little Rock, Arkansas, 72205, United States
Veterans Affairs Medical Center - Little Rock (McClellan) | Little Rock, Arkansas, 72205, United States
Veterans Affairs Medical Center - Long Beach | Long Beach, California, 90822, United States
USC/Norris Comprehensive Cancer Center | Los Angeles, California, 90033-0800, United States
Jonsson Comprehensive Cancer Center, UCLA | Los Angeles, California, 90095-1781, United States
Beckman Research Institute, City of Hope | Los Angeles, California, 91010, United States
Veterans Affairs Outpatient Clinic - Martinez | Martinez, California, 94553, United States
CCOP - Bay Area Tumor Institute | Oakland, California, 94609-3305, United States
University of California Davis Medical Center | Sacramento, California, 95817, United States
CCOP - Santa Rosa Memorial Hospital | Santa Rosa, California, 95403, United States
David Grant Medical Center | Travis Air Force Base, California, 94535, United States
Veterans Affairs Medical Center - Denver | Denver, Colorado, 80220, United States
University of Colorado Cancer Center | Denver, Colorado, 80262, United States
CCOP - Atlanta Regional | Atlanta, Georgia, 30342-1701, United States
Cancer Research Center of Hawaii | Honolulu, Hawaii, 96813, United States
CCOP - Central Illinois | Decatur, Illinois, 62526, United States
Veterans Affairs Medical Center - Hines (Hines Junior VA Hospital) | Hines, Illinois, 60141, United States
Loyola University Medical Center | Maywood, Illinois, 60153, United States
University of Kansas Medical Center | Kansas City, Kansas, 66160-7357, United States
CCOP - Wichita | Wichita, Kansas, 67214-3882, United States
Veterans Affairs Medical Center - Wichita | Wichita, Kansas, 67218, United States
Veterans Affairs Medical Center - Lexington | Lexington, Kentucky, 40511-1093, United States
Albert B. Chandler Medical Center, University of Kentucky | Lexington, Kentucky, 40536-0084, United States
MBCCOP - LSU Medical Center | New Orleans, Louisiana, 70112, United States
Tulane University School of Medicine | New Orleans, Louisiana, 70112, United States
Veterans Affairs Medical Center - New Orleans | New Orleans, Louisiana, 70112, United States
Louisiana State University Health Sciences Center - Shreveport | Shreveport, Louisiana, 71130-3932, United States
Veterans Affairs Medical Center - Shreveport | Shreveport, Louisiana, 71130, United States
Boston Medical Center | Boston, Massachusetts, 02118, United States
Veterans Affairs Medical Center - Boston (Jamaica Plain) | Jamaica Plain, Massachusetts, 02130, United States
Veterans Affairs Medical Center - Ann Arbor | Ann Arbor, Michigan, 48105, United States
University of Michigan Comprehensive Cancer Center | Ann Arbor, Michigan, 48109-0752, United States
Veterans Affairs Medical Center - Detroit | Detroit, Michigan, 48201-1932, United States
Barbara Ann Karmanos Cancer Institute | Detroit, Michigan, 48201, United States
Henry Ford Hospital | Detroit, Michigan, 48202, United States
CCOP - Grand Rapids Clinical Oncology Program | Grand Rapids, Michigan, 49503, United States
Providence Hospital - Southfield | Southfield, Michigan, 48075-9975, United States
CCOP - Metro-Minnesota | Saint Louis Park, Minnesota, 55416, United States
Veterans Affairs Medical Center - Biloxi | Biloxi, Mississippi, 39531-2410, United States
University of Mississippi Medical Center | Jackson, Mississippi, 39216-4505, United States
Veterans Affairs Medical Center - Jackson | Jackson, Mississippi, 39216, United States
Keesler Medical Center - Keesler AFB | Keesler AFB, Mississippi, 39534-2576, United States
Veterans Affairs Medical Center - Kansas City | Kansas City, Missouri, 64128, United States
CCOP - Kansas City | Kansas City, Missouri, 64131, United States
St. Louis University Health Sciences Center | Saint Louis, Missouri, 63110-0250, United States
CCOP - St. Louis-Cape Girardeau | Saint Louis, Missouri, 63141, United States
CCOP - Cancer Research for the Ozarks | Springfield, Missouri, 65807, United States
CCOP - Montana Cancer Consortium | Billings, Montana, 59101, United States
Veterans Affairs Medical Center - Albuquerque | Albuquerque, New Mexico, 87108-5138, United States
MBCCOP - University of New Mexico HSC | Albuquerque, New Mexico, 87131, United States
Veterans Affairs Medical Center - Brooklyn | Brooklyn, New York, 11209, United States
Herbert Irving Comprehensive Cancer Center | New York, New York, 10032, United States
Barrett Cancer Center, The University Hospital | Cincinnati, Ohio, 45219, United States
Veterans Affairs Medical Center - Cincinnati | Cincinnati, Ohio, 45220-2288, United States
Cleveland Clinic Cancer Center | Cleveland, Ohio, 44195, United States
CCOP - Columbus | Columbus, Ohio, 43206, United States
Veterans Affairs Medical Center - Dayton | Dayton, Ohio, 45428, United States
CCOP - Dayton | Kettering, Ohio, 45429, United States
Oklahoma Medical Research Foundation | Oklahoma City, Oklahoma, 73104, United States
Veterans Affairs Medical Center - Oklahoma City | Oklahoma City, Oklahoma, 73104, United States
Oregon Cancer Center at Oregon Health Sciences University | Portland, Oregon, 97201-3098, United States
Veterans Affairs Medical Center - Portland | Portland, Oregon, 97207, United States
CCOP - Columbia River Program | Portland, Oregon, 97213, United States
CCOP - Greenville | Greenville, South Carolina, 29615, United States
CCOP - Upstate Carolina | Spartanburg, South Carolina, 29303, United States
Veterans Affairs Medical Center - Nashville | Nashville, Tennessee, 37212, United States
Vanderbilt Cancer Center | Nashville, Tennessee, 37232-6838, United States
Brooke Army Medical Center | Fort Sam Houston, Texas, 78234, United States
University of Texas Medical Branch | Galveston, Texas, 77555-1329, United States
Texas Tech University Health Science Center | Lubbock, Texas, 79423, United States
University of Texas Health Science Center at San Antonio | San Antonio, Texas, 78284-7811, United States
Veterans Affairs Medical Center - San Antonio (Murphy) | San Antonio, Texas, 78284, United States
Veterans Affairs Medical Center - Temple | Temple, Texas, 76504, United States
CCOP - Scott and White Hospital | Temple, Texas, 76508, United States
Huntsman Cancer Institute | Salt Lake City, Utah, 84132, United States
Veterans Affairs Medical Center - Salt Lake City | Salt Lake City, Utah, 84148, United States
CCOP - Virginia Mason Research Center | Seattle, Washington, 98101, United States
Swedish Cancer Institute | Seattle, Washington, 98104, United States
Veterans Affairs Medical Center - Seattle | Seattle, Washington, 98108, United States
Puget Sound Oncology Consortium | Seattle, Washington, 98109, United States
CCOP - Northwest | Tacoma, Washington, 98405-0986, United States
Location Countries

United States

Verification Date

January 2013

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Label: Immumosuppression, IFN-a, ProMACE-CytaBOM

Type: Experimental

Description: 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.

Study Design Info

Allocation: N/A

Intervention Model: Single Group Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov