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

Sponsor

Southwest Oncology Group (Other)

Overall Status

Completed

CT.gov ID

NCT00002657

Collaborator

National Cancer Institute (NCI) (NIH), Eastern Cooperative Oncology Group (Other)

Enrollment

Locations

Arm

194

Duration (Months)

0.2

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma Multiple Myeloma and Plasma Cell Neoplasm	Biological: bleomycin sulfate Biological: recombinant interferon alfa Drug: cyclophosphamide Drug: cytarabine Drug: doxorubicin hydrochloride Drug: etoposide Drug: methotrexate Drug: prednisone Drug: vincristine sulfate Procedure: conventional surgery Radiation: radiation therapy	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

20 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

May 1, 1995

Actual Primary Completion Date :

Nov 1, 2003

Actual Study Completion Date :

Jul 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Biological: bleomycin sulfate 5 mg/m^2 Biological: recombinant interferon alfa 3.0 x 10^6 IU/m^2 Drug: cyclophosphamide 650 mg/m^2 Drug: cytarabine 300 mg/m^2 Drug: doxorubicin hydrochloride 25 mg/m^2 Other Names: adriamycin Drug: etoposide 120 mg/m^2 Drug: methotrexate 120 mg/m^2 Drug: prednisone dose varies during initial immunosuppression. During chemotherapy, 60 mg/m^2. Drug: vincristine sulfate 1.4 mg/m^2 Procedure: conventional surgery Simple excision, for those patients who have resectable disease after initial immunosuppression. Radiation: radiation therapy For treatment of localized disease that remains after initial immunosuppression.

Arm

Intervention/Treatment

Experimental: 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.

Biological: bleomycin sulfate

5 mg/m^2

Biological: recombinant interferon alfa

3.0 x 10^6 IU/m^2

Drug: cyclophosphamide

650 mg/m^2

Drug: cytarabine

300 mg/m^2

Drug: doxorubicin hydrochloride

25 mg/m^2

Other Names:

adriamycin

Drug: etoposide

120 mg/m^2

Drug: methotrexate

120 mg/m^2

Drug: prednisone

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

Drug: vincristine sulfate

1.4 mg/m^2

Procedure: conventional surgery

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

Radiation: radiation therapy

For treatment of localized disease that remains after initial immunosuppression.

Outcome Measures

Primary Outcome Measures

Response [every 3 months while on protocol treatment]

Secondary Outcome Measures

overall survival [every 3 months while on treatment, then every 6 months thereafter]

Eligibility Criteria

Criteria

Ages Eligible for Study:

15 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	MBCCOP - University of South Alabama	Mobile	Alabama	United States	36688
2	CCOP - Greater Phoenix	Phoenix	Arizona	United States	85006-2726
3	Veterans Affairs Medical Center - Phoenix (Hayden)	Phoenix	Arizona	United States	85012
4	Veterans Affairs Medical Center - Tucson	Tucson	Arizona	United States	85723
5	Arizona Cancer Center	Tucson	Arizona	United States	85724
6	University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
7	Veterans Affairs Medical Center - Little Rock (McClellan)	Little Rock	Arkansas	United States	72205
8	Veterans Affairs Medical Center - Long Beach	Long Beach	California	United States	90822
9	USC/Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033-0800
10	Jonsson Comprehensive Cancer Center, UCLA	Los Angeles	California	United States	90095-1781
11	Beckman Research Institute, City of Hope	Los Angeles	California	United States	91010
12	Veterans Affairs Outpatient Clinic - Martinez	Martinez	California	United States	94553
13	CCOP - Bay Area Tumor Institute	Oakland	California	United States	94609-3305
14	University of California Davis Medical Center	Sacramento	California	United States	95817
15	CCOP - Santa Rosa Memorial Hospital	Santa Rosa	California	United States	95403
16	David Grant Medical Center	Travis Air Force Base	California	United States	94535
17	Veterans Affairs Medical Center - Denver	Denver	Colorado	United States	80220
18	University of Colorado Cancer Center	Denver	Colorado	United States	80262
19	CCOP - Atlanta Regional	Atlanta	Georgia	United States	30342-1701
20	Cancer Research Center of Hawaii	Honolulu	Hawaii	United States	96813
21	CCOP - Central Illinois	Decatur	Illinois	United States	62526
22	Veterans Affairs Medical Center - Hines (Hines Junior VA Hospital)	Hines	Illinois	United States	60141
23	Loyola University Medical Center	Maywood	Illinois	United States	60153
24	University of Kansas Medical Center	Kansas City	Kansas	United States	66160-7357
25	CCOP - Wichita	Wichita	Kansas	United States	67214-3882
26	Veterans Affairs Medical Center - Wichita	Wichita	Kansas	United States	67218
27	Veterans Affairs Medical Center - Lexington	Lexington	Kentucky	United States	40511-1093
28	Albert B. Chandler Medical Center, University of Kentucky	Lexington	Kentucky	United States	40536-0084
29	MBCCOP - LSU Medical Center	New Orleans	Louisiana	United States	70112
30	Tulane University School of Medicine	New Orleans	Louisiana	United States	70112
31	Veterans Affairs Medical Center - New Orleans	New Orleans	Louisiana	United States	70112
32	Louisiana State University Health Sciences Center - Shreveport	Shreveport	Louisiana	United States	71130-3932
33	Veterans Affairs Medical Center - Shreveport	Shreveport	Louisiana	United States	71130
34	Boston Medical Center	Boston	Massachusetts	United States	02118
35	Veterans Affairs Medical Center - Boston (Jamaica Plain)	Jamaica Plain	Massachusetts	United States	02130
36	Veterans Affairs Medical Center - Ann Arbor	Ann Arbor	Michigan	United States	48105
37	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109-0752
38	Veterans Affairs Medical Center - Detroit	Detroit	Michigan	United States	48201-1932
39	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201
40	Henry Ford Hospital	Detroit	Michigan	United States	48202
41	CCOP - Grand Rapids Clinical Oncology Program	Grand Rapids	Michigan	United States	49503
42	Providence Hospital - Southfield	Southfield	Michigan	United States	48075-9975
43	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota	United States	55416
44	Veterans Affairs Medical Center - Biloxi	Biloxi	Mississippi	United States	39531-2410
45	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216-4505
46	Veterans Affairs Medical Center - Jackson	Jackson	Mississippi	United States	39216
47	Keesler Medical Center - Keesler AFB	Keesler AFB	Mississippi	United States	39534-2576
48	Veterans Affairs Medical Center - Kansas City	Kansas City	Missouri	United States	64128
49	CCOP - Kansas City	Kansas City	Missouri	United States	64131
50	St. Louis University Health Sciences Center	Saint Louis	Missouri	United States	63110-0250
51	CCOP - St. Louis-Cape Girardeau	Saint Louis	Missouri	United States	63141
52	CCOP - Cancer Research for the Ozarks	Springfield	Missouri	United States	65807
53	CCOP - Montana Cancer Consortium	Billings	Montana	United States	59101
54	Veterans Affairs Medical Center - Albuquerque	Albuquerque	New Mexico	United States	87108-5138
55	MBCCOP - University of New Mexico HSC	Albuquerque	New Mexico	United States	87131
56	Veterans Affairs Medical Center - Brooklyn	Brooklyn	New York	United States	11209
57	Herbert Irving Comprehensive Cancer Center	New York	New York	United States	10032
58	Barrett Cancer Center, The University Hospital	Cincinnati	Ohio	United States	45219
59	Veterans Affairs Medical Center - Cincinnati	Cincinnati	Ohio	United States	45220-2288
60	Cleveland Clinic Cancer Center	Cleveland	Ohio	United States	44195
61	CCOP - Columbus	Columbus	Ohio	United States	43206
62	Veterans Affairs Medical Center - Dayton	Dayton	Ohio	United States	45428
63	CCOP - Dayton	Kettering	Ohio	United States	45429
64	Oklahoma Medical Research Foundation	Oklahoma City	Oklahoma	United States	73104
65	Veterans Affairs Medical Center - Oklahoma City	Oklahoma City	Oklahoma	United States	73104
66	Oregon Cancer Center at Oregon Health Sciences University	Portland	Oregon	United States	97201-3098
67	Veterans Affairs Medical Center - Portland	Portland	Oregon	United States	97207
68	CCOP - Columbia River Program	Portland	Oregon	United States	97213
69	CCOP - Greenville	Greenville	South Carolina	United States	29615
70	CCOP - Upstate Carolina	Spartanburg	South Carolina	United States	29303
71	Veterans Affairs Medical Center - Nashville	Nashville	Tennessee	United States	37212
72	Vanderbilt Cancer Center	Nashville	Tennessee	United States	37232-6838
73	Brooke Army Medical Center	Fort Sam Houston	Texas	United States	78234
74	University of Texas Medical Branch	Galveston	Texas	United States	77555-1329
75	Texas Tech University Health Science Center	Lubbock	Texas	United States	79423
76	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78284-7811
77	Veterans Affairs Medical Center - San Antonio (Murphy)	San Antonio	Texas	United States	78284
78	Veterans Affairs Medical Center - Temple	Temple	Texas	United States	76504
79	CCOP - Scott and White Hospital	Temple	Texas	United States	76508
80	Huntsman Cancer Institute	Salt Lake City	Utah	United States	84132
81	Veterans Affairs Medical Center - Salt Lake City	Salt Lake City	Utah	United States	84148
82	CCOP - Virginia Mason Research Center	Seattle	Washington	United States	98101
83	Swedish Cancer Institute	Seattle	Washington	United States	98104
84	Veterans Affairs Medical Center - Seattle	Seattle	Washington	United States	98108
85	Puget Sound Oncology Consortium	Seattle	Washington	United States	98109
86	CCOP - Northwest	Tacoma	Washington	United States	98405-0986