|Phase III||Treatment||Closed||16 to 59||EORTC-PARMA|
I. Compare event-free survival and duration of response of adult patients with relapsed non-Hodgkin's lymphoma who, after at least a PR following two courses of salvage chemotherapy, are randomized to involved-field radiotherapy followed by intensive high-dose chemotherapy with BEAC (carmustine/etoposide/cytarabine/cyclophosphamide) and autologous bone marrow therapy vs. a continuation of their conventional chemotherapy with DHAP (dexamethasone/cisplatin/cytarabine) followed by involved-field radiotherapy. II. Compare the crude survival in both groups. III. Confirm that the bone marrow therapy strategy does not lead to a greater than 15% mortality. IV. Evaluate and compare toxicities of the two randomized treatments.
Histologically proven, intermediate- or high-grade non- Hodgkin's lymphoma in first relapse following previous CR Cytologically proven relapse or mediastinal relapse of previous histologically proven diffuse lymphoma allowed Evaluable disease required (unless patient is in second CR following surgical excision of a proven relapse) First-line doxorubicin-containing regimen or "good regimen" without doxorubicin (as determined by Steering Committee) given prior to relapse required Radiotherapy alone as first-line therapy is not allowed Cumulative lifetime doxorubicin dose must be less than 550 mg/sqm No CNS involvement at relapse No marrow involvement at relapse Requirements for randomization are as follows: PR or CR following 2 courses of salvage chemotherapy (other than dexamethasone/cisplatin/cytarabine) Bone marrow harvested either before relapse or after the first course of salvage chemotherapy Normal bone marrow cellularity required Purged marrow is not allowed Original entry criteria continue to be met with regard to organ function
Biologic therapy: At least 2 weeks since immunotherapy Chemotherapy: See Disease Characteristics At least 2 weeks since chemotherapy Endocrine therapy: Not specified Radiotherapy: At least 2 weeks since radiotherapy Surgery: Prior surgical excision of first relapse allowed
Age: 16 to 59 Performance status: Karnofsky 60-100% Life expectancy: At least 12 weeks Hematopoietic: Not specified Hepatic: Bilirubin no greater than 1.0 mg/dl (17 micromoles/liter) Renal: Creatinine no greater than 1.7 mg/dl (150 micromoles/liter) Cardiovascular: Technetium scan greater than 50% normal No evidence of cardiac dysfunction on EKG Pulmonary: Vital capacity at least 70% of predicted Diffusion capacity at least 70% of predicted
71 patients will be required for each randomized treatment. Assuming a 50% rate of eligibility for randomization, a total of 280 patients will be needed. Accrual time is estimated at about 3 years.
All patients receive 2 courses of salvage chemotherapy on Regimen A, after which, if they still meet eligibility requirements, those in PR and CR are randomized to Arms I and II. Regimen A: 3-Drug Combination Chemotherapy. DHAP: Dexamethasone, DM, NSC-34521; Cisplatin, CDDP, NSC-119875; Cytarabine, ARA-C, NSC-63878. Arm I: Radiotherapy followed by 4-Drug Combination Chemotherapy plus (in Europe only) Urothelial Protection; followed by Autologous Bone Marrow Therapy. Involved-field irradiation using megavoltage equipment or, where appropriate, electrons; followed by BEAC: Carmustine, BCNU, NSC-409962; Etoposide, VP-16, NSC-141540; ARA-C; Cyclophosphamide, CTX, NSC-26271; plus (in Europe) Mesna, NSC-113891; followed by autologous marrow infusion. Arm II: 3-Drug Combination Chemotherapy followed by Radiotherapy. DHAP; followed by involved-field irradiation as in Arm I.Published Results
Blay J, Gomez F, Sebban C, et al.: The International Prognostic Index correlates to survival in patients with aggressive lymphoma in relapse: analysis of the PARMA trial. Parma Group. Blood 92 (10): 3562-8, 1998.[PUBMED Abstract]
Philip T, Guglielmi C, Chauvin F, et al.: Autologous bone marrow transplantation (ABMT) versus (vs) conventional chemotherapy (DHAP) in relapsed non Hodgkin lymphoma (NHL): final analysis of the PARMA randomized study (216 patients). [Abstract] Proceedings of the American Society of Clinical Oncology 14: A-1220, 390, 1995.
Trial Lead Organizations
European Organization for Research and Treatment of Cancer
|Thierry Philip, MD, Protocol chair|
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.