Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Related Publications
Trial Contact Information
Related Information
Registry Information

Alternate Title

Biological Therapy and Combination Chemotherapy in Treating Patients With Lymphomatoid Granulomatosis

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Active	12 and over	NCI	NCI-94-C-0074 NCI-MB-325, NCT00018993

Special Category: NIH Clinical Center trial

Objectives

1. Determine the long-term efficacy of interferon alfa in patients with lymphomatoid granulomatosis.
2. Determine the long-term efficacy of etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab in patients with grade III lymphomatoid granulomatosis OR in patients who fail interferon therapy.
3. Determine the response in patients treated with these regimens.

Entry Criteria

Disease Characteristics:

• Histologically confirmed grade I, II, or III lymphomatoid granulomatosis of any stage

Prior/Concurrent Therapy:

Biologic therapy

• Not specified

Chemotherapy

• Prior chemotherapy allowed

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Patient Characteristics:

Age:

• 12 and over

Performance status:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Bilirubin no greater than 2.5 mg/dL (unless liver involvement)(for patients receiving study chemotherapy)

Renal:

• Creatinine no greater than 1.5 mg/dL*

  OR

• Creatinine clearance at least 40 mL/min*

 [Note: *For patients receiving study chemotherapy]

Cardiovascular:

• LVEF greater than 40% on MUGA if more than 450 mg/m² of doxorubicin was previously received*
• No congestive heart failure*
• No coronary artery disease with angina pectoris*

 [Note: *For patients receiving study chemotherapy]

Other:

• No poor medical or psychiatric risk
• HIV negative
• Not pregnant or nursing
• Negative pregnancy test

Expected Enrollment

A total of 70 patients will be accrued for this study.

Outcomes

Response and long-term efficacy of alpha interferon at completion of study treatment and 5 years later
Response and long-term efficacy of dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) at completion of study treatment and 5 years later

Immunologic phenotype, Epstein-barr virus (EBV) viral loads, and molecular markers of clonality as measured by tissue and blood samples during study treatment

Outline

Patients are stratified according to disease status (grade I or II lymphomatoid granulomatosis [LYG] vs grade III LYG).

Regimen A (grade I or II LYG):

• Patients receive interferon alfa (IFN-A) subcutaneously (SC) 3 times a week for at least 1-3 years. Patients with complete remission or stable disease receive IFN-A for an additional 12 months. Patients with progressive disease proceed to chemotherapy on regimen B.

Regimen B (grade III LYG OR disease progression on IFN-A):

• Patients receive rituximab IV on day 1; doxorubicin IV, etoposide IV, and vincristine IV continuously on days 1-4; cyclophosphamide IV on day 5; and oral prednisone twice a day on days 1-5. Patients receive filgrastim (G-CSF) SC beginning on day 6 and continuing until blood counts recover. Treatment repeats every 21 days for 6-8 courses.

  Patients who achieve a partial remission on chemotherapy receive IFN-A as in regimen A beginning 4 weeks after completion of chemotherapy.

Patients receiving treatment on regimen A with evidence of disease progression or aggressive lymphoma in the CNS who are experiencing neurological symptoms warranting treatment OR receiving treatment on regimen B may be treated with intrathecal methotrexate or cytarabine and/or craniospinal radiotherapy. Patients with progressive disease after intrathecal chemotherapy may receive radiotherapy. Patients with parenchymal involvement of the brain receive standard whole brain radiotherapy.

Patients with progressive disease on chemotherapy and/or IFN-A may receive standard treatment including rituximab.

Patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1 year, and then annually thereafter.

Wilson WH, Gutierrez M, Raffeld M, et al.: Lymphomatoid granulomatosis: phase II study of dose-adjusted interferon-α or EPOCH chemotherapy. [Abstract] Blood 94 (10 Pt 1): A-2668, 599a, 1999.

Wilson WH, Kingma DW, Wittes R, et al.: Lymphomatoid granulomatosis (LYG) is an EBV-positive B-cell lymphoproliferative disorder responsive to alpha-interferon (Ifn). [Abstract] Proceedings of the American Society of Clinical Oncology 13: A-1294, 381, 1994.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

Wyndham Wilson, MD, PhD, Protocol chair		Ph: 301-435-2415

U.S.A.
Maryland
	Bethesda
	NCI - Center for Cancer Research
		Clinical Trials Office - NCI - Center for Cancer Research	Ph:  888-624-1937
	Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
		Patient Recruitment	Ph:  1-888-NCI-1937

Related Information

Web site for additional information

Registry Information
Official Title		Treatment & Natural History of Lymphomatoid Granulomatosis
Trial Start Date		1994-02-09
Trial Completion Date		2011-12-31 (estimated)
Registered in ClinicalTrials.gov		NCT00018993
Date Submitted to PDQ		1996-02-26
Information Last Verified		2008-11-30