RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. It is not yet known which combination chemotherapy regimen is more effective for intermediate-grade or immunoblastic non-Hodgkin's lymphoma.

PURPOSE: Randomized phase III trial to compare the effectiveness of two combination chemotherapy regimens in treating patients who have intermediate-grade or immunoblastic non-Hodgkin's lymphoma.

Condition	Treatment or Intervention	Phase
Lymphoma	Drug: bleomycin  Drug: cisplatin  Drug: cyclophosphamide  Drug: cytarabine  Drug: doxorubicin  Drug: etoposide  Drug: idarubicin  Drug: ifosfamide  Drug: mesna  Drug: methylprednisolone  Drug: mitoxantrone  Drug: prednisone  Drug: vincristine	Phase III

Further Study Details: 

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) vs. 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 vs. 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 vs. the International Index System.

PROTOCOL 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.

Ages Eligible for Study:  15 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--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

--Prior/Concurrent Therapy--

• No prior therapy

--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)

Texas
      University of Texas - MD Anderson Cancer Center, Houston,  Texas,  77030,  United States
Brazil
      Faculdade de Medicina do ABC, Sao Paulo,  01224--010,  Brazil
Chile
      Clinica Alemana, Santiago,  5951,  Chile

Study chairs or principal investigators

Fernando Cabanillas,  Study Chair,  M.D. Anderson Cancer Center   

Study ID Numbers:  CDR0000063574; MDA-DM-94017; NCI-T94-0040D
Record last reviewed:  June 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00002565
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08