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 II	Treatment	Closed	15 and over	NCI	SWOG-9349

Objectives

I.  Compare the complete response rate, time to treatment failure, and overall 
survival of patients with stage II, III, or IV intermediate or high grade 
non-Hodgkin's lymphoma when treated with dose-intensive cyclophosphamide, 
vincristine, doxorubicin, and prednisone (CHOP) with filgrastim (G-CSF) versus 
dose-intensive cyclophosphamide, doxorubicin, etoposide, prednisone, 
cytarabine, bleomycin, vincristine, methotrexate, and leucovorin 
(ProMACE/CytaBOM) with G-CSF.

II.  Assess the toxic effects and side effects associated with these regimens.

III.  Correlate clinicopathologic results with those from protocols SWOG-8819, 
SWOG-9245, and SWOG-8947 using the central serum and tissue repositories.

Entry Criteria

Disease Characteristics:

Biopsy-proven intermediate or high grade non-Hodgkin's lymphoma of one of the
following histologic types (Working Formulation groups D through H and J):
  Follicular large cell
  Diffuse large cell
  Diffuse mixed cell
  Diffuse small cleaved cell
  Immunoblastic large cell
  Small noncleaved cell

No lymphoblastic lymphoma

No transformed lymphoma

Pathology review of diagnostic specimen by SWOG Pathology Office required
  Biopsy section must be adequate to determine architectural pattern (bone
  marrow biopsy, needle aspirate, or needle biopsy is not sufficient)

Bulky stage II and stage III/IV disease eligible (Ann Arbor criteria)
  Bulky disease defined as a mediastinal mass greater than one-third of the
  maximum chest diameter or any other mass at least 10 cm in maximum diameter

No clinical or laboratory evidence of CNS involvement by lymphoma

Bidimensionally measurable disease with clearly defined margins required
  Lesion at least 0.5 cm on medical photograph (skin or oral lesion) or plain
   x-ray (no bone lesions)
  Lesion on CT, MRI, or other imaging scan with both diameters greater than
   the distance between cuts of the imaging study
  Palpable lesion with both diameters at least 2 cm

Bone marrow aspirate and biopsy required within 42 days of registration unless
positive within the last 6 months

CT of abdomen and pelvis required within 28 days prior to registration unless
negative within 42 days prior to registration

No prior diagnosis of lymphoma, Hodgkin's disease, myelodysplastic syndrome,
or leukemia (even if disease-free for more than 5 years)

A new classification scheme for adult non-Hodgkin's lymphoma has been adopted
by PDQ.  The terminology of "indolent" or "aggressive" lymphoma will replace
the former terminology of "low", "intermediate", or "high" grade lymphoma. 
However, this protocol uses the former terminology.

Prior/Concurrent Therapy:

Biologic therapy:
 Not specified

Chemotherapy:
 No prior chemotherapy for lymphoma
  Prednisone or other corticosteroids are not considered chemotherapy

Endocrine therapy:
 Not specified

Radiotherapy:
 No prior radiotherapy for lymphoma

Surgery:
 Not specified

Patient Characteristics:

Age:
 15 and over

Performance status:
 SWOG 0-2

Hematopoietic:
 Not specified

Hepatic:
 Bilirubin no greater than 1.5 times normal

Renal:
 Creatinine no greater than 2 times normal
 Creatinine clearance at least 60 mL/min

Cardiovascular:
 No coronary artery disease, cardiomyopathy, congestive heart failure, or
  dysrhythmia requiring therapy
 Left ventricular ejection fraction normal by MUGA within 42 days prior to
  registration if cardiac history is questionable

Pulmonary:
 DLCO greater than 50%

Other:
 No known AIDS or ARC
 No second malignancy within 5 years except adequately treated
  nonmelanomatous skin cancer or carcinoma in situ of the cervix
 Not pregnant or nursing 
 Effective contraception required of fertile patients

Expected Enrollment

98 patients/arm will be accrued in approximately 18 months.

Outline

Randomized study.  The following acronyms are used:
  ARA-C   Cytarabine, NSC-63878
  BLEO    Bleomycin, NSC-125066
  CTX     Cyclophosphamide, NSC-26271
  DOX     Doxorubicin, NSC-123127
  G-CSF   Granulocyte Colony-Stimulating Factor (Amgen), NSC-614629
  CF      Leucovorin calcium, NSC-3590
  MTX     Methotrexate, NSC-740
  PRED    Prednisone, NSC-10023
  VCR     Vincristine, NSC-67574
  VP-16   Etoposide, NSC-141540

Arm I:  4-Drug Combination Chemotherapy with Hematopoietic Rescue.  CHOP:  
CTX; VCR; DOX; PRED; with G-CSF.

Arm II:  8-Drug Combination Chemotherapy with Hematopoietic Rescue.  
ProMACE/CytaBOM:  CTX; DOX; VP-16; PRED; ARA-C; BLEO; VCR; MTX/CF; and G-CSF.

Blayney DW, LeBlanc ML, Grogan T, et al.: Dose-intense chemotherapy every 2 weeks with dose-intense cyclophosphamide, doxorubicin, vincristine, and prednisone may improve survival in intermediate- and high-grade lymphoma: a phase II study of the Southwest Oncology Group (SWOG 9349). J Clin Oncol 21 (13): 2466-73, 2003.[PUBMED Abstract]

Blayney DW, LeBlanc ML, Fisher RI, et al.: Dose-intense CHOPx2 therapy of intermediate grade lymphoma -- a phase II study of the Southwest Oncology Group (SWOG). [Abstract] Blood 98 (11 Pt 1): A-1448, 2001.

Trial Contact Information

Trial Lead Organizations

Southwest Oncology Group

Richard Fisher, MD, Protocol chair(Contact information may not be current)		Ph: 708-216-9000