Combination Chemotherapy in Treating Patients With Intermediate-Grade or Immunoblastic Non-Hodgkin's Lymphoma

OBJECTIVES:

I. Compare, in a randomized setting, the time to treatment failure and the survival of
patients with poor-prognosis intermediate-grade or immunoblastic lymphoma treated with the
standard regimen of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) versus the
new alternating triple therapy (ATT) of IdSHAP (idarubicin, cisplatin, cytarabine,
methylprednisolone), BIdCOS (idarubicin, vincristine, bleomycin, cyclophosphamide,
methylprednisolone), and MINE (mesna, ifosfamide, mitoxantrone, etoposide).

II. Compare the complete response rate achieved with ATT versus standard CHOP.

III. Assess the feasibility of delivering full standard doses of chemotherapy to patients
over 60 years of age who receive granulocyte colony stimulating factor support.

IV. Compare the predictive capability of the M.D. Anderson Tumor Score System versus the
International Index System.

OUTLINE: Randomized study. The following acronyms are used: ARA-C Cytarabine, NSC-63878 BLEO
Bleomycin, NSC-125066 CDDP Cisplatin, NSC-119875 CTX Cyclophosphamide, NSC-26271 DHAD
Mitoxantrone, NSC-301739 DOX Doxorubicin, NSC-123127 G-CSF Granulocyte Colony-Stimulating
Factor (source unspecified) IDA Idarubicin, NSC-256439 IFF Ifosfamide, NSC-109724 MePRDL
Methylprednisolone succinate Mesna Mercaptoethane sulfonate, NSC-113891 PRED Prednisone,
NSC-10023 VCR Vincristine, NSC-67574 VP-16 Etoposide, NSC-141540

Arm I: Sequential 4-, 5-, and 3-Drug Combination Chemotherapy. IdSHAP: IDA/CDDP/ARA-C/MePRDL;
followed by BIdCOS: BLEO/IDA/CTX/VCR/MePRDL; followed by MINE: Mesna/IFF/DHAD/VP-16.

Arm II: 4-Drug Combination Chemotherapy. CHOP: CTX/DOX/VCR/PRED.

PROJECTED ACCRUAL: 218 evaluable patients will be accrued over approximately 31 months to
this multicenter study. If either arm is significantly inferior at interim analyses after 31
and 60 treatment failures, consideration will be given to early closure.

DISEASE CHARACTERISTICS: Previously untreated non-Hodgkin's lymphoma (NHL) of one of the
following histologies: Diffuse large cell Follicular large non-cleaved cell Diffuse mixed
cell Immunoblastic At least 2 of the following poor-prognosis factors required: Age over 60
Performance status greater than 1 Any elevation of LDH More than 1 extranodal site Ann
Arbor stage III or IV T- and B-cell NHL eligible if meeting all above criteria No primary
CNS lymphoma Brain involvement eligible if not primary

PATIENT CHARACTERISTICS: Age: Over 15 Performance status: Any status Hematopoietic: (unless
secondary to tumor) Absolute granulocyte count at least 1,000/mm3 Platelet count at least
100,000/mm3 Hepatic: Bilirubin less than 1.5 mg/dL Elevation secondary to tumor discussed
with study chairman Renal: (unless secondary to tumor) Creatinine no greater than 1.5 mg/dL
Cardiovascular: Left ventricular ejection fraction greater than 55% by echocardiography
Pulmonary: No chronic obstructive or restrictive lung disease Pulmonary consultation
required in cases of doubt Other: No HIV infection No prior malignancy with less than a 90%
5-year survival probability No patients unable or unlikely to adhere to treatment because
of geographic, economic, emotional, or social factors No unwillingness to accept blood
product transfusions or other supportive measures (e.g., antibiotics)

PRIOR CONCURRENT THERAPY: No prior therapy