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

Phase 2
Completed
Conditions
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Interventions
Biological: bleomycin sulfate
Biological: recombinant interferon alfa
Procedure: conventional surgery
Radiation: radiation therapy
Registration Number
NCT00002657
Lead Sponsor
SWOG Cancer Research Network
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
20
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Immumosuppression, IFN-a, ProMACE-CytaBOMbleomycin sulfateDoses 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.
Immumosuppression, IFN-a, ProMACE-CytaBOMrecombinant interferon alfaDoses 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.
Immumosuppression, IFN-a, ProMACE-CytaBOMconventional surgeryDoses 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.
Immumosuppression, IFN-a, ProMACE-CytaBOMradiation therapyDoses 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.
Immumosuppression, IFN-a, ProMACE-CytaBOMvincristine sulfateDoses 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.
Immumosuppression, IFN-a, ProMACE-CytaBOMcytarabineDoses 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.
Immumosuppression, IFN-a, ProMACE-CytaBOMcyclophosphamideDoses 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.
Immumosuppression, IFN-a, ProMACE-CytaBOMdoxorubicin hydrochlorideDoses 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.
Immumosuppression, IFN-a, ProMACE-CytaBOMetoposideDoses 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.
Immumosuppression, IFN-a, ProMACE-CytaBOMprednisoneDoses 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.
Immumosuppression, IFN-a, ProMACE-CytaBOMmethotrexateDoses 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.
Primary Outcome Measures
NameTimeMethod
Responseevery 3 months while on protocol treatment
Secondary Outcome Measures
NameTimeMethod
overall survivalevery 3 months while on treatment, then every 6 months thereafter

Trial Locations

Locations (86)

MBCCOP - University of South Alabama

🇺🇸

Mobile, Alabama, United States

CCOP - Greater Phoenix

🇺🇸

Phoenix, Arizona, United States

Veterans Affairs Medical Center - Phoenix (Hayden)

🇺🇸

Phoenix, Arizona, United States

Veterans Affairs Medical Center - Tucson

🇺🇸

Tucson, Arizona, United States

Arizona Cancer Center

🇺🇸

Tucson, Arizona, United States

University of Arkansas for Medical Sciences

🇺🇸

Little Rock, Arkansas, United States

Veterans Affairs Medical Center - Little Rock (McClellan)

🇺🇸

Little Rock, Arkansas, United States

Veterans Affairs Medical Center - Long Beach

🇺🇸

Long Beach, California, United States

USC/Norris Comprehensive Cancer Center

🇺🇸

Los Angeles, California, United States

Jonsson Comprehensive Cancer Center, UCLA

🇺🇸

Los Angeles, California, United States

Scroll for more (76 remaining)
MBCCOP - University of South Alabama
🇺🇸Mobile, Alabama, United States

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