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

Sponsor

M.D. Anderson Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00002565

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Arms

152.4

Actual Duration (Months)

20.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Lymphoma	Biological: bleomycin sulfate Drug: CHOP regimen Drug: cisplatin Drug: cyclophosphamide Drug: cytarabine Drug: doxorubicin hydrochloride Drug: etoposide Drug: idarubicin Drug: ifosfamide Drug: mesna Drug: methylprednisolone Drug: mitoxantrone hydrochloride Drug: prednisone Drug: vincristine sulfate	Phase 3

Detailed Description

OBJECTIVES:

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).
Compare the complete response rate achieved with ATT versus standard CHOP.
Assess the feasibility of delivering full standard doses of chemotherapy to patients over 60 years of age who receive granulocyte colony stimulating factor support.
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.

Study Design

Study Type:

Interventional

Actual Enrollment :

61 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

RANDOMIZED COMPARISON OF ALTERNATING TRIPLE THERAPY ("ATT") VERUS CHOP IN PATIENTS WITH INTERMEDIATE GRADE LYMPHOMAS AND IMMUNOBLASTIC LYMPHOMAS WITH INTERNATIONAL INDEX 2-5

Actual Study Start Date :

May 25, 1994

Actual Primary Completion Date :

Feb 5, 2007

Actual Study Completion Date :

Feb 5, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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. Alternating triple therapy (ATT) of IdSHAP (idarubicin, cisplatin, cytarabine, methylprednisolone), BIdCOS (idarubicin, vincristine, bleomycin, cyclophosphamide, methylprednisolone), and MINE (mesna, ifosfamide, mitoxantrone, etoposide).	Biological: bleomycin sulfate Drug: cisplatin Drug: cyclophosphamide Drug: cytarabine Drug: etoposide Drug: idarubicin Drug: ifosfamide Drug: mesna Drug: methylprednisolone Drug: mitoxantrone hydrochloride Drug: vincristine sulfate
Experimental: Arm II 4-Drug Combination Chemotherapy. CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone): CTX/DOX/VCR/PRED.	Drug: CHOP regimen Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: prednisone Drug: vincristine sulfate

Arm

Intervention/Treatment

Experimental: 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. Alternating triple therapy (ATT) of IdSHAP (idarubicin, cisplatin, cytarabine, methylprednisolone), BIdCOS (idarubicin, vincristine, bleomycin, cyclophosphamide, methylprednisolone), and MINE (mesna, ifosfamide, mitoxantrone, etoposide).

Biological: bleomycin sulfate

Drug: cisplatin

Drug: cyclophosphamide

Drug: cytarabine

Drug: etoposide

Drug: idarubicin

Drug: ifosfamide

Drug: mesna

Drug: methylprednisolone

Drug: mitoxantrone hydrochloride

Drug: vincristine sulfate

Experimental: Arm II

4-Drug Combination Chemotherapy. CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone): CTX/DOX/VCR/PRED.

Drug: CHOP regimen

Drug: cyclophosphamide

Drug: doxorubicin hydrochloride

Drug: prednisone

Drug: vincristine sulfate

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

15 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Texas - MD Anderson Cancer Center	Houston	Texas	United States	77030
2	Faculdade de Medicina do ABC	Sao Paulo		Brazil	01224--010
3	Clinica Alemana	Santiago		Chile	5951