Clinical trial NCT00002657: SWOG-9239 Reduction of Immunosuppression Plus Interferon Alfa and Combination Chemotherapy in Treating Patients With Malignant Tumors That Develop After Organ Transplant
Official title: Phase II Trial of Sequential Modification of Immunosuppression, Interferon Alpha, and Promace-Cytabom For Treatment of Post-Cardiac Transplant Lymphoproliferation.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Keywords: isolated plasmacytoma of bone
extramedullary plasmacytoma
refractory multiple myeloma
Waldenstrom macroglobulinemia
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
stage I small lymphocytic lymphoma
stage I grade 1 follicular lymphoma
stage I grade 2 follicular lymphoma
stage I grade 3 follicular lymphoma
stage I adult diffuse small cleaved cell lymphoma
stage I adult diffuse mixed cell lymphoma
stage I adult diffuse large cell lymphoma
stage I adult immunoblastic large cell lymphoma
stage I adult Burkitt lymphoma
stage II small lymphocytic lymphoma
stage II grade 1 follicular lymphoma
stage II grade 2 follicular lymphoma
stage II grade 3 follicular lymphoma
stage II adult diffuse small cleaved cell lymphoma
stage II adult diffuse mixed cell lymphoma
stage II adult diffuse large cell lymphoma
stage II adult immunoblastic large cell lymphoma
stage II adult Burkitt lymphoma
stage III small lymphocytic lymphoma
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage III grade 3 follicular lymphoma
stage III adult diffuse small cleaved cell lymphoma
stage III adult diffuse mixed cell lymphoma
stage III adult diffuse large cell lymphoma
stage III adult immunoblastic large cell lymphoma
stage III adult Burkitt lymphoma
stage IV small lymphocytic lymphoma
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma
stage IV adult diffuse small cleaved cell lymphoma
stage IV adult diffuse mixed cell lymphoma
stage IV adult diffuse large cell lymphoma
stage IV adult immunoblastic large cell lymphoma
stage IV adult Burkitt lymphoma
recurrent small lymphocytic lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult Burkitt lymphoma
contiguous stage II grade 1 follicular lymphoma
contiguous stage II grade 2 follicular lymphoma
contiguous stage II grade 3 follicular lymphoma
contiguous stage II adult diffuse small cleaved cell lymphoma
contiguous stage II adult diffuse mixed cell lymphoma
contiguous stage II adult immunoblastic large cell lymphoma
contiguous stage II adult diffuse large cell lymphoma
contiguous stage II adult Burkitt lymphoma
noncontiguous stage II grade 1 follicular lymphoma
noncontiguous stage II grade 2 follicular lymphoma
noncontiguous stage II grade 3 follicular lymphoma
noncontiguous stage II adult diffuse small cleaved cell lymphoma
noncontiguous stage II adult diffuse mixed cell lymphoma
noncontiguous stage II adult immunoblastic large cell lymphoma
noncontiguous stage II adult diffuse large cell lymphoma
noncontiguous stage II adult Burkitt lymphoma
noncontiguous stage II small lymphocytic lymphoma
noncontiguous stage II marginal zone lymphoma
recurrent marginal zone lymphoma
stage I marginal zone lymphoma
stage III marginal zone lymphoma
stage IV marginal zone lymphoma
contiguous stage II marginal zone lymphoma
contiguous stage II small lymphocytic lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma
Lead sponsor: SWOG Cancer Research Network
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
name: Eastern Cooperative Oncology Group
First posted: 2004-06-22
Enrollment: 20
Sex: ALL
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Response
timeFrame: every 3 months while on protocol treatment
Secondary outcomes:
measure: overall survival
timeFrame: every 3 months while on treatment, then every 6 months thereafter
Other outcomes:
Locations:
city: Mobile
country: United States
facility: MBCCOP - University of South Alabama
state: Alabama
city: Phoenix
country: United States
facility: CCOP - Greater Phoenix
state: Arizona
city: Phoenix
country: United States
facility: Veterans Affairs Medical Center - Phoenix (Hayden)
state: Arizona
city: Tucson
country: United States
facility: Veterans Affairs Medical Center - Tucson
state: Arizona
city: Tucson
country: United States
facility: Arizona Cancer Center
state: Arizona
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Little Rock
country: United States
facility: Veterans Affairs Medical Center - Little Rock (McClellan)
state: Arkansas
city: Long Beach
country: United States
facility: Veterans Affairs Medical Center - Long Beach
state: California
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center
state: California
city: Los Angeles
country: United States
facility: Jonsson Comprehensive Cancer Center, UCLA
state: California
city: Los Angeles
country: United States
facility: Beckman Research Institute, City of Hope
state: California
city: Martinez
country: United States
facility: Veterans Affairs Outpatient Clinic - Martinez
state: California
city: Oakland
country: United States
facility: CCOP - Bay Area Tumor Institute
state: California
city: Sacramento
country: United States
facility: University of California Davis Medical Center
state: California
city: Santa Rosa
country: United States
facility: CCOP - Santa Rosa Memorial Hospital
state: California
city: Travis Air Force Base
country: United States
facility: David Grant Medical Center
state: California
city: Denver
country: United States
facility: Veterans Affairs Medical Center - Denver
state: Colorado
city: Denver
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Atlanta
country: United States
facility: CCOP - Atlanta Regional
state: Georgia
city: Honolulu
country: United States
facility: Cancer Research Center of Hawaii
state: Hawaii
city: Decatur
country: United States
facility: CCOP - Central Illinois
state: Illinois
city: Hines
country: United States
facility: Veterans Affairs Medical Center - Hines (Hines Junior VA Hospital)
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Wichita
country: United States
facility: CCOP - Wichita
state: Kansas
city: Wichita
country: United States
facility: Veterans Affairs Medical Center - Wichita
state: Kansas
city: Lexington
country: United States
facility: Veterans Affairs Medical Center - Lexington
state: Kentucky
city: Lexington
country: United States
facility: Albert B. Chandler Medical Center, University of Kentucky
state: Kentucky
city: New Orleans
country: United States
facility: MBCCOP - LSU Medical Center
state: Louisiana
city: New Orleans
country: United States
facility: Tulane University School of Medicine
state: Louisiana
city: New Orleans
country: United States
facility: Veterans Affairs Medical Center - New Orleans
state: Louisiana
city: Shreveport
country: United States
facility: Louisiana State University Health Sciences Center - Shreveport
state: Louisiana
city: Shreveport
country: United States
facility: Veterans Affairs Medical Center - Shreveport
state: Louisiana
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Jamaica Plain
country: United States
facility: Veterans Affairs Medical Center - Boston (Jamaica Plain)
state: Massachusetts
city: Ann Arbor
country: United States
facility: Veterans Affairs Medical Center - Ann Arbor
state: Michigan
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Detroit
country: United States
facility: Veterans Affairs Medical Center - Detroit
state: Michigan
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Grand Rapids
country: United States
facility: CCOP - Grand Rapids Clinical Oncology Program
state: Michigan
city: Southfield
country: United States
facility: Providence Hospital - Southfield
state: Michigan
city: Saint Louis Park
country: United States
facility: CCOP - Metro-Minnesota
state: Minnesota
city: Biloxi
country: United States
facility: Veterans Affairs Medical Center - Biloxi
state: Mississippi
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Jackson
country: United States
facility: Veterans Affairs Medical Center - Jackson
state: Mississippi
city: Keesler AFB
country: United States
facility: Keesler Medical Center - Keesler AFB
state: Mississippi
city: Kansas City
country: United States
facility: Veterans Affairs Medical Center - Kansas City
state: Missouri
city: Kansas City
country: United States
facility: CCOP - Kansas City
state: Missouri
city: Saint Louis
country: United States
facility: St. Louis University Health Sciences Center
state: Missouri
city: Saint Louis
country: United States
facility: CCOP - St. Louis-Cape Girardeau
state: Missouri
city: Springfield
country: United States
facility: CCOP - Cancer Research for the Ozarks
state: Missouri
city: Billings
country: United States
facility: CCOP - Montana Cancer Consortium
state: Montana
city: Albuquerque
country: United States
facility: Veterans Affairs Medical Center - Albuquerque
state: New Mexico
city: Albuquerque
country: United States
facility: MBCCOP - University of New Mexico HSC
state: New Mexico
city: Brooklyn
country: United States
facility: Veterans Affairs Medical Center - Brooklyn
state: New York
city: New York
country: United States
facility: Herbert Irving Comprehensive Cancer Center
state: New York
city: Cincinnati
country: United States
facility: Barrett Cancer Center, The University Hospital
state: Ohio
city: Cincinnati
country: United States
facility: Veterans Affairs Medical Center - Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Cancer Center
state: Ohio
city: Columbus
country: United States
facility: CCOP - Columbus
state: Ohio
city: Dayton
country: United States
facility: Veterans Affairs Medical Center - Dayton
state: Ohio
city: Kettering
country: United States
facility: CCOP - Dayton
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma Medical Research Foundation
state: Oklahoma
city: Oklahoma City
country: United States
facility: Veterans Affairs Medical Center - Oklahoma City
state: Oklahoma
city: Portland
country: United States
facility: Oregon Cancer Center at Oregon Health Sciences University
state: Oregon
city: Portland
country: United States
facility: Veterans Affairs Medical Center - Portland
state: Oregon
city: Portland
country: United States
facility: CCOP - Columbia River Program
state: Oregon
city: Greenville
country: United States
facility: CCOP - Greenville
state: South Carolina
city: Spartanburg
country: United States
facility: CCOP - Upstate Carolina
state: South Carolina
city: Nashville
country: United States
facility: Veterans Affairs Medical Center - Nashville
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt Cancer Center
state: Tennessee
city: Fort Sam Houston
country: United States
facility: Brooke Army Medical Center
state: Texas
city: Galveston
country: United States
facility: University of Texas Medical Branch
state: Texas
city: Lubbock
country: United States
facility: Texas Tech University Health Science Center
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: San Antonio
country: United States
facility: Veterans Affairs Medical Center - San Antonio (Murphy)
state: Texas
city: Temple
country: United States
facility: Veterans Affairs Medical Center - Temple
state: Texas
city: Temple
country: United States
facility: CCOP - Scott and White Hospital
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Salt Lake City
country: United States
facility: Veterans Affairs Medical Center - Salt Lake City
state: Utah
city: Seattle
country: United States
facility: CCOP - Virginia Mason Research Center
state: Washington
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Seattle
country: United States
facility: Veterans Affairs Medical Center - Seattle
state: Washington
city: Seattle
country: United States
facility: Puget Sound Oncology Consortium
state: Washington
city: Tacoma
country: United States
facility: CCOP - Northwest
state: Washington
Study officials:
affiliation: Loyola University
name: Lode J. Swinnen, MD
role: STUDY_CHAIR
affiliation: Robert H. Lurie Cancer Center
name: Leo I. Gordon, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.