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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Closed 18 and over BRMP-9110 NCI-92-C-0203

Objectives

I.  Determine the toxicity of ProMACE-CytaBOM 
(prednisone/cyclophosphamide/doxorubicin/etoposide and 
cytarabine/bleomycin/vincristine/methotrexate) using 5-day oral etoposide 
(VP-16) in patients with low-grade and selected intermediate-grade lymphomas.

II.  Estimate the complete response rate, using standard pathologic 
examination, to ProMACE-CytaBOM with 5-day oral VP-16 in untreated and 
previously treated patients with low-grade and selected intermediate-grade 
lymphomas.

III.  Estimate the complete response rate to this regimen using molecular 
analysis (PCR) in patients with appropriate chromosomal translocations.

IV.  Determine the toxicity of postinduction immunotoxin therapy with 
monoclonal antibody anti-B4/blocked ricin immunoconjugate (MOAB anti-B4/bR).

V.  Estimate the response rate of MOAB anti-B4/bR in patients with persistent 
disease (peripheral or residual bone marrow involvement by microscopy) 
following chemotherapy.

VI.  Rule out a response rate of 50 +/- 15% for the ability of immunotoxin 
treatment to eliminate bcl-2-positive cells from the bone marrow as detected 
by PCR.

VII.  Assess and compare disease-free and overall survival in patients whose 
marrow has been determined by PCR to be negative for malignant cells with 
patients whose marrows are morphologically negative but PCR-positive for 
malignant cells.

VIII.  Determine the overall survival of patients treated with this regimen.

Entry Criteria

Disease Characteristics:

Pathologically confirmed, Stage III/IV non-Hodgkin's lymphoma
of the following types:
  Well-differentiated lymphocytic
  Diffuse, intermediately differentiated lymphocytic
  Follicular small cleaved cell
  Follicular mixed cell
  Diffuse small cleaved cell

Circulating lymphocytes documented to be B lymphocytes of a
single light chain required

  Greater than 15,000 malignant lymphocytes/microliter in
  peripheral blood with phenotype characteristic of CLL and
  lymph node histology consistent with well-differentiated
  lymphocytic lymphoma excludes

  Lymph node biopsy characteristic of nodular lymphoma and
  peripheral blood lymphocytosis allowed

Previously untreated patients preferred, but up to 2
chemotherapy regimens given for a total of no more than 12
months allowed

No prior or current CNS lymphoma

Prior/Concurrent Therapy:

Prior combined modality therapy allowed

Biologic therapy:
  No prior ricin-containing compound
  No prior mouse antibody
  At least 4 weeks since prior immunotherapy (exceptions
     allowed for patients with clearly progressive disease if
     toxicity has resolved)

Chemotherapy:
  Up to 2 prior chemotherapy regimens given for a total
     duration of therapy of no more than 12 months allowed
  Progressive disease during prior ProMACE-CytaBOM excludes
  At least 4 weeks since prior chemotherapy (exceptions allowed
     for patients with clearly progressive disease if toxicity
     has resolved)

Endocrine therapy:
  At least 4 weeks since prior hormonal therapy (exceptions
  allowed for patients with clearly progressive disease if
  toxicity has resolved)

Radiotherapy:
  No prior total-body irradiation
  At least 4 weeks since prior radiotherapy (exceptions allowed
     for patients with clearly progressive disease if toxicity
     has resolved)

Surgery:
  Not specified

Patient Characteristics:

Age:
  18 and over

Performance status:
  Karnofsky 70-100%

Life expectancy:
  Greater than 3 months

Hematopoietic:
  Not given

Hepatic:
  Bilirubin no greater than 1.5 mg/dl (unless elevation
     secondary to lymphoma or Gilbert's disease)
  SGOT/SGPT no greater than 3.5 x ULN
  PT/PTT within normal limits

Renal:
  Creatinine no greater than 1.5 mg/dl (unless elevation
  secondary to lymphoma)

Other:
  HIV and HBsAg seronegative
  No active infection
  No medical or psychiatric condition that would
     compromise tolerance to treatment
  No second malignancy except:
     Curatively treated nonmelanomatous skin cancer
     Effectively treated in situ carcinoma of the cervix
  No nursing women
  Negative pregnancy test required of fertile women
  Effective contraception required of fertile patients

Expected Enrollment

64 patients will be treated.

Outline

Nonrandomized study.  Patients are treated on Regimen A, then Regimen B.

Regimen A:  8-Drug Combination Chemotherapy with Leucovorin Rescue.  
ProMACE-CytaBOM:  Prednisone, PRED, NSC-10023; Cyclophosphamide, CTX, 
NSC-26271; Doxorubicin, DOX, NSC-123127; Etoposide, VP-16, NSC-141540; 
Cytarabine, ARA-C, NSC-63878; Bleomycin, BLEO, NSC-125066; Vincristine, VCR, 
NSC-67574; Methotrexate, MTX, NSC-740; with Leucovorin calcium, CF, NSC-3590.

Regimen B:  Biological Response Modifier Therapy.  Monoclonal Antibody 
Anti-B4/Blocked Ricin Immunoconjugate, MOAB anti-B4/bR.

Trial Contact Information

Trial Lead Organizations

Clinical Research Branch

Dan Longo, MD, FACP, Protocol chair		Ph: 410-558-8190