SWOG-9320 Combination Chemotherapy, Radiation Therapy, and Antiviral Therapy in Treating Patients With AIDS-Related Lymphoma

Condition(s) targeted: Lymphoma

Intervention: bleomycin sulfate (Biological); filgrastim (Biological); cyclophosphamide (Drug); cytarabine (Drug); doxorubicin hydrochloride (Drug); etoposide (Drug); leucovorin calcium (Drug); methotrexate (Drug); prednisone (Drug); trimethoprim-sulfamethoxazole (Drug); vincristine sulfate (Drug); radiation therapy (Radiation); Intrathecal cytarabine (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: Southwest Oncology Group

Official(s) and/or principal investigator(s):
Lode J. Swinnen, MD, Study Chair, Affiliation: Loyola University

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage cancer cells. Antiviral therapy may be effective treatment for AIDS-related lymphoma. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy, radiation therapy, and antiviral therapy in treating patients who have AIDS-related lymphoma.

Official title: Study of Promace-Cytabom With Trimethoprim Sulfamethoxazole, Zidovudine (AZT), and Granulocyte Colony Stimulating Factor (G-CSF) in Patients With AIDS-Related Lymphoma, Phase II

Study design: Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Response

Detailed description: OBJECTIVES: I. Assess the response rate of AIDS-related lymphoma to ProMACE-CytaBOM (cyclophosphamide, doxorubicin, etoposide, prednisone, cytarabine, bleomycin, vincristine, methotrexate). II. Assess the toxic effects of ProMACE-CytaBOM in patients with AIDS-related lymphoma. III. Evaluate whether the incorporation of filgrastim (G-CSF) into the regimen allows treatment with full doses of the myelotoxic agents in these patients. IV. Determine whether intensive CNS treatment with intrathecal cytarabine and whole-brain irradiation prevents meningeal relapse or controls meningeal lymphomatous involvement in these patients. OUTLINE: Patients are stratified according to participating institution and descriptive factors: histopathology (diffuse large cleaved/noncleaved and immunoblastic lymphomas vs all others), CD4 count (less than 50 vs 50 or more cells/mm3), prior opportunistic infection (yes vs no), performance status (0 and 1 vs 2), concurrent AZT (yes vs no), concurrent protease inhibitors (yes vs no), marrow involvement (yes vs no). Patients receive ProMACE-CytaBOM regimen as follows: Cyclophosphamide, doxorubicin, and etoposide IV on day 1 Cytarabine, bleomycin, vincristine, and methotrexate IV on day 8 Oral prednisone on days 1-14 Oral leucovorin calcium every 6 hours for 4 doses on day 9 Patients also receive filgrastim (G-CSF) subcutaneously on days 9-20 and oral co-trimoxazole 3 days a week throughout treatment, plus antiretroviral therapy at the discretion of the treating physician. Treatment repeats every 21 days for a maximum of 6 courses. Patients with progressive disease are removed from study after 2 courses. Remaining patients receive an additional 2 treatment courses and are then restaged. Patients without stable or progressive disease receive 2 more courses in the absence of unacceptable toxicity. Patients with positive bone marrow at study entry receive CNS prophylaxis with 5 evenly spaced doses of intrathecal cytarabine during the first 2 treatment courses and on day 1 of each subsequent course. Patients with positive CSF cytology at study entry receive intrathecal cytarabine on days 1-5 of the first treatment course and on day 1 of each subsequent course if CSF negative after 5 daily doses. Patients whose CSF remains positive after 5 days receive 5 evenly spaced doses of intrathecal methotrexate during the second treatment course. Patients with negative bone marrow and CSF cytology at study entry receive 5 evenly spaced doses of intrathecal cytarabine within 1 month of systemic therapy. All patients achieving a complete or partial response following systemic therapy and intrathecal cytarabine receive cranial irradiation to all meningeal surfaces. Patients are followed monthly for 1 year, every 2 months for 1 year, every 3 months for 1 year, then annually thereafter. PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study over approximately 2 years.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

DISEASE CHARACTERISTICS: Histologically proven intermediate or high grade non-Hodgkin's lymphoma of one of the following histologies: Follicular, predominantly large cell Diffuse, small cleaved cell Diffuse mixed, small and large cell Diffuse, large cell (cleaved or noncleaved) Immunoblastic, large cell Small noncleaved cell, Burkitt's or non-Burkitt's No lymphoblastic lymphoma Prior diagnosis of AIDS or HIV positivity required Confirmation of HIV antibody status by Western blot mandatory Bidimensionally measurable or evaluable disease No primary CNS lymphoma Concurrent registration on protocol SWOG-8947 (central serum repository) required PATIENT CHARACTERISTICS: Age: Over 18 Performance status: SWOG 0-2 Hematopoietic: Absolute neutrophil count at least 500/mm3 Platelet count at least 75,000/mm3 Hepatic: AST no greater than 1. 5 times normal Alkaline phosphatase no greater than 1. 5 times normal LDH no greater than 1. 5 times normal PT/PTT normal Renal: Creatinine no greater than 2. 0 times normal Creatinine clearance at least 60 mL/min Cardiovascular: No serious abnormalities on EKG No history of severe coronary artery disease No history of cardiomyopathy, congestive heart failure, or arrhythmia Other: No active uncontrolled infection No active second malignancy within 5 years except adequately treated nonmelanoma skin cancer or adequately treated carcinoma in situ of the cervix Not pregnant or nursing Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: No prior chemotherapy or radiotherapy for lymphoma

MBCCOP - University of South Alabama, Mobile, Alabama 36688, United States

CCOP - Greater Phoenix, Phoenix, Arizona 85006-2726, United States

Veterans Affairs Medical Center - Phoenix (Hayden), Phoenix, Arizona 85012, United States

Arizona Cancer Center, Tucson, Arizona 85724, United States

Veterans Affairs Medical Center - Tucson, Tucson, Arizona 85723, United States

University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, United States

Veterans Affairs Medical Center - Little Rock (McClellan), Little Rock, Arkansas 72205, United States

Veterans Affairs Medical Center - Long Beach, Long Beach, California 90822, United States

Beckman Research Institute, City of Hope, Los Angeles, California 91010, United States

Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, California 90095-1781, United States

USC/Norris Comprehensive Cancer Center, Los Angeles, California 90033-0800, United States

Veterans Affairs Outpatient Clinic - Martinez, Martinez, California 94553, United States

CCOP - Bay Area Tumor Institute, Oakland, California 94609-3305, United States

Chao Family Comprehensive Cancer Center, Orange, California 92868, United States

University of California Davis Medical Center, Sacramento, California 95817, United States

CCOP - Santa Rosa Memorial Hospital, Santa Rosa, California 95403, United States

David Grant Medical Center, Travis Air Force Base, California 94535, United States

University of Colorado Cancer Center, Denver, Colorado 80262, United States

Veterans Affairs Medical Center - Denver, Denver, Colorado 80220, United States

CCOP - Atlanta Regional, Atlanta, Georgia 30342-1701, United States

Cancer Research Center of Hawaii, Honolulu, Hawaii 96813, United States

Tripler Army Medical Center, Honolulu, Hawaii 96859-5000, United States

CCOP - Central Illinois, Decatur, Illinois 62526, United States

Veterans Affairs Medical Center - Hines (Hines Junior VA Hospital), Hines, Illinois 60141, United States

Loyola University Medical Center, Maywood, Illinois 60153, United States

University of Kansas Medical Center, Kansas City, Kansas 66160-7357, United States

CCOP - Wichita, Wichita, Kansas 67214-3882, United States

Veterans Affairs Medical Center - Wichita, Wichita, Kansas 67218, United States

Albert B. Chandler Medical Center, University of Kentucky, Lexington, Kentucky 40536-0084, United States

Veterans Affairs Medical Center - Lexington, Lexington, Kentucky 40511-1093, United States

MBCCOP - LSU Medical Center, New Orleans, Louisiana 70112, United States

Tulane University School of Medicine, New Orleans, Louisiana 70112, United States

Veterans Affairs Medical Center - New Orleans, New Orleans, Louisiana 70112, United States

Louisiana State University Health Sciences Center - Shreveport, Shreveport, Louisiana 71130-3932, United States

Veterans Affairs Medical Center - Shreveport, Shreveport, Louisiana 71130, United States

Boston Medical Center, Boston, Massachusetts 02118, United States

Veterans Affairs Medical Center - Boston (Jamaica Plain), Jamaica Plain, Massachusetts 02130, United States

University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan 48109-0752, United States

Veterans Affairs Medical Center - Ann Arbor, Ann Arbor, Michigan 48105, United States

Barbara Ann Karmanos Cancer Institute, Detroit, Michigan 48201, United States

Henry Ford Hospital, Detroit, Michigan 48202, United States

Veterans Affairs Medical Center - Detroit, Detroit, Michigan 48201-1932, United States

CCOP - Grand Rapids Clinical Oncology Program, Grand Rapids, Michigan 49503, United States

Providence Hospital - Southfield, Southfield, Michigan 48075-9975, United States

Veterans Affairs Medical Center - Biloxi, Biloxi, Mississippi 39531-2410, United States

University of Mississippi Medical Center, Jackson, Mississippi 39216-4505, United States

Veterans Affairs Medical Center - Jackson, Jackson, Mississippi 39216, United States

Keesler Medical Center - Keesler AFB, Keesler AFB, Mississippi 39534-2576, United States

CCOP - Kansas City, Kansas City, Missouri 64131, United States

Veterans Affairs Medical Center - Kansas City, Kansas City, Missouri 64128, United States

CCOP - St. Louis-Cape Girardeau, Saint Louis, Missouri 63141, United States

St. Louis University Health Sciences Center, Saint Louis, Missouri 63110-0250, United States

CCOP - Cancer Research for the Ozarks, Springfield, Missouri 65807, United States

CCOP - Montana Cancer Consortium, Billings, Montana 59101, United States

MBCCOP - University of New Mexico HSC, Albuquerque, New Mexico 87131, United States

Veterans Affairs Medical Center - Albuquerque, Albuquerque, New Mexico 87108-5138, United States

Herbert Irving Comprehensive Cancer Center, New York, New York 10032, United States

Barrett Cancer Center, The University Hospital, Cincinnati, Ohio 45219, United States

Veterans Affairs Medical Center - Cincinnati, Cincinnati, Ohio 45220-2288, United States

Cleveland Clinic Cancer Center, Cleveland, Ohio 44195, United States

CCOP - Columbus, Columbus, Ohio 43206, United States

Veterans Affairs Medical Center - Dayton, Dayton, Ohio 45428, United States

CCOP - Dayton, Kettering, Ohio 45429, United States

Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, United States

Veterans Affairs Medical Center - Oklahoma City, Oklahoma City, Oklahoma 73104, United States

CCOP - Columbia River Program, Portland, Oregon 97213, United States

Oregon Cancer Center at Oregon Health Sciences University, Portland, Oregon 97201-3098, United States

Veterans Affairs Medical Center - Portland, Portland, Oregon 97207, United States

CCOP - Greenville, Greenville, South Carolina 29615, United States

CCOP - Upstate Carolina, Spartanburg, South Carolina 29303, United States

Simmons Cancer Center - Dallas, Dallas, Texas 75235-9154, United States

Brooke Army Medical Center, Fort Sam Houston, Texas 78234, United States

University of Texas Medical Branch, Galveston, Texas 77555-1329, United States

Texas Tech University Health Science Center, Lubbock, Texas 79423, United States

University of Texas Health Science Center at San Antonio, San Antonio, Texas 78284-7811, United States

Veterans Affairs Medical Center - San Antonio (Murphy), San Antonio, Texas 78284, United States

CCOP - Scott and White Hospital, Temple, Texas 76508, United States

Veterans Affairs Medical Center - Temple, Temple, Texas 76504, United States

Huntsman Cancer Institute, Salt Lake City, Utah 84132, United States

Veterans Affairs Medical Center - Salt Lake City, Salt Lake City, Utah 84148, United States

CCOP - Virginia Mason Research Center, Seattle, Washington 98101, United States

Puget Sound Oncology Consortium, Seattle, Washington 98109, United States

Swedish Cancer Institute, Seattle, Washington 98104, United States

Veterans Affairs Medical Center - Seattle, Seattle, Washington 98108, United States

CCOP - Northwest, Tacoma, Washington 98405-0986, United States

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: June 1994
Last updated: January 22, 2013