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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Closed	16 and over	NCI	EST-1484

Objectives

I.  Determine the complete response rate and toxicity of chemotherapy with 
CHOP (cyclophosphamide/adriamycin/vincristine/prednisone) for early stage 
non-Hodgkin's lymphoma of unfavorable (diffuse) histologic subtypes.
II.  Compare the effect of radiotherapy (administered to sites of pretreatment 
clinical involvement) following documented chemotherapy-induced complete 
response vs. chemotherapy alone with respect to duration of complete response, 
sites of relapse, survival, and toxicity.
III.  Assess the ability of radiotherapy to convert partial responders after 
chemotherapy (who have persistent localized disease) to restaged complete 
responders.
IV.  Determine the duration of complete response, sites of relapse, survival, 
and toxicity in patients who achieve complete response after radiotherapy.

Entry Criteria

Disease Characteristics:

Histologically confirmed Stage I/IE/II/IIE non-Hodgkin's
lymphoma that is residual following incomplete resection

One of the following histologic subtypes required:

  Diffuse large cell (histiocytic or immunoblastic)
  Diffuse mixed small and large cell (mixed histiocytic
     lymphocytic)
  Diffuse small cleaved cell (lymphocytic, poorly
     differentiated)

Clinical or pathologic Stage I or IE tumors must have at
least one of the following:

  Mediastinal or retroperitoneal involvement
  Bulky disease (tumor mass 10 cm or greater)
  Extranodal IE disease of any size

Involvement of the following extranodal sites allowed:

  Waldeyer's ring (nasopharynx, tonsil, or base of tongue)
  Thyroid
  Lung or pleura (contiguous direct extension from adjacent
     nodes must be demonstrated)
  Breast
  Gastrointestinal tract (stomach, small bowel, or colon)
  Gynecologic organs (ovary, uterus, cervix)
  Bone (solitary direct extension from a nodal mass)
  Skin (direct extension from a nodal mass)

Extranodal disease (i.e., lung mass, bone involvement, skin
lesion) with noncontiguous extension from a lymph node region
excluded

Percutaneous bone marrow biopsy must be negative; abdominal
CT scan required

Disease may be measurable or nonmeasurable

Prior/Concurrent Therapy:

Biologic therapy:
  Not specified

Chemotherapy:
  No prior chemotherapy

Endocrine therapy:
  Not specified

Radiotherapy:
  No prior radiotherapy

Surgery:
  Total prior resection not allowed
  Recovery from prior surgery required (generally at least 2
     weeks postoperative)
  No postoperative evidence of active infection or
     complications

Patient Characteristics:

Age:
  16 and over

Performance status:
  Not specified

Hematopoietic:
  WBC at least 4,000
  Platelets at least 100,000

Hepatic:
  Bilirubin no greater than 2.0 mg/dl

Renal:
  Creatinine no greater than 2.0 mg/dl
  BUN no greater than 30 mg/dl

Cardiovascular:
  No CHF
  No severe coronary insufficiency
  No MI within 3 months

Other:
  No active uncontrolled infection (bacterial, viral, fungal)
  No poorly controlled diabetes mellitus that would preclude
     high-dose prednisone
  No active uncontrolled nonmalignant duodenal ulcer

Expected Enrollment

It is estimated that a total of 250 patients, of whom 175 will be complete 
responders, will be entered over 5 years.  An accrual rate of 50 patients/year 
is anticipated.  Because the CR rate was lower than expected and the rate of 
patient refusal of radiotherapy was higher than expected, the accrual target 
was increased to 325 patients.  It is estimated that this increased accrual 
will require an additional 11 months of patient entry.

Outline

Randomized study.  Partial responders on Arms I and II enter Regimen A.
Arm I:  4-Drug Combination Chemotherapy.  CHOP:  Cyclophosphamide, CTX, 
NSC-26271; Adriamycin, ADR, NSC-123127; Vincristine, VCR, NSC-67574; 
Prednisone, PRED, NSC-10023.
Arm II:  4-Drug Combination Chemotherapy followed by Radiotherapy (for 
complete responders).  CHOP; followed by irradiation of sites of pretreatment 
involvement using megavoltage equipment.
Regimen A:  Radiotherapy.  Irradiation of sites of pretreatment involvement 
and contiguous uninvolved regions using megavoltage equipment.

Horning SJ, Weller E, Kim K, et al.: Chemotherapy with or without radiotherapy in limited-stage diffuse aggressive non-Hodgkin's lymphoma: Eastern Cooperative Oncology Group study 1484. J Clin Oncol 22 (15): 3032-8, 2004.[PUBMED Abstract]

Glick JH, Kim K, Earle J, et al.: An ECOG randomized phase III trial of CHOP vs. CHOP + radiotherapy (XRT) for intermediate grade early stage non-Hodgkin's lymphoma (NHL). [Abstract] Proceedings of the American Society of Clinical Oncology 14: A-1221, 391, 1995.

Trial Contact Information

Trial Lead Organizations

Eastern Cooperative Oncology Group

John Glick, MD, Protocol chair		Ph: 215-662-6334 Email: glickjh@mail.med.upenn.edu