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

This study has been completed.
Sponsor:
Collaborators:
Eastern Cooperative Oncology Group
Information provided by (Responsible Party):
Southwest Oncology Group
ClinicalTrials.gov Identifier:
NCT00002657
First received: November 1, 1999
Last updated: January 22, 2013
Last verified: January 2013
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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.

Resource links provided by NLM:


Further study details as provided by Southwest Oncology Group:

Primary Outcome Measures:
  • Response [ Time Frame: every 3 months while on protocol treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • overall survival [ Time Frame: every 3 months while on treatment, then every 6 months thereafter ] [ Designated as safety issue: No ]

Enrollment: 20
Study Start Date: May 1995
Study Completion Date: July 2011
Primary Completion Date: November 2003 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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.

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

Ages Eligible for Study:   15 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00002657

  Show 86 Study Locations
Sponsors and Collaborators
Southwest Oncology Group
Eastern Cooperative Oncology Group
Investigators
Study Chair: Lode J. Swinnen, MD Loyola University
Study Chair: Leo I. Gordon, MD Robert H. Lurie Cancer Center
  More Information

Additional Information:
Publications:
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.
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.

Responsible Party: Southwest Oncology Group
ClinicalTrials.gov Identifier: NCT00002657     History of Changes
Other Study ID Numbers: CDR0000064200, SWOG-9239, E-S9239, U10CA032102
Study First Received: November 1, 1999
Last Updated: January 22, 2013
Health Authority: United States: Federal Government

Keywords provided by Southwest Oncology Group:
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

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Lymphatic Diseases
Cyclophosphamide
Methotrexate
Liposomal doxorubicin
Etoposide
Interferons
Doxorubicin
Prednisone
Vincristine
Bleomycin
Interferon-alpha
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 16, 2014