Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information

Basic Trial Information

Objectives

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.

Entry Criteria

Disease Characteristics:

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

Prior/Concurrent Therapy:

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

Patient Characteristics:

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

Expected Enrollment

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.

Outline

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.

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 Contact Information

Trial Lead Organizations

European Organization for Research and Treatment of Cancer

Thierry Philip, MD, Protocol chair		Ph: 33-4-78-78-26-45 Email: philip@lyon.fnclcc.fr

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