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 physiologic 18 to 65 Other DFCI-94025 NCI-V94-0582

Objectives

I.  Evaluate the toxicity and feasibility of sequential murine monoclonal 
antibody anti-B4 conjugated to blocked ricin (anti-B4-bR) and EPOCH 
(cyclophosphamide/doxorubicin/prednisone/vincristine/etoposide) in multiply 
relapsed patients with B-cell non-Hodgkin's lymphoma.

II.  Determine the rate of human antimurine and antiricin antibody production 
after this treatment.

III.  Assess the preliminary activity of anti-B4-bR/EPOCH after 2 courses.

Entry Criteria

Disease Characteristics:

Histologically confirmed B-cell non-Hodgkin's lymphoma that has failed at
least 2 chemotherapy regimens
  Reviewed by the Department of Pathology, Brigham and Women's Hospital
  No history of CNS involvement

Tumor cells reactive with anti-B4, anti-B1, or L26 antibodies
  Documented by flow cytometry or immunoperoxidase staining
  Tissue from original diagnosis, relapse, or protocol entry

Disease evaluable by physical exam, chest x-ray, CT, MRI, gallium scan, or
bone marrow exam

Prior/Concurrent Therapy:

Biologic therapy:
  No prior therapy with murine monoclonal antibodies

Chemotherapy:
  At least 3 weeks since chemotherapy
  1 prior regimen of CHOP or CHOP variant required, e.g.:
     M-BACOD           ProMACE-MOPP
     ProMACE-CytaBOM   COP-BLAM
     MACOP-B

Endocrine therapy:
  No concurrent estrogen therapy
  No concurrent corticosteroids

Radiotherapy:
  No prior CNS irradiation of 3,000 Gy or more
  At least 3 weeks since radiotherapy

Surgery:
  At least 3 weeks since major surgery

Patient Characteristics:

Age:
  Physiologic 18 to 65

Performance status:
  ECOG 0-2

Life expectancy:
  At least 3 months

Hematopoietic:
  ANC at least 1,000
  Platelets at least 100,000
  Hct at least 25%

Hepatic:
  Bilirubin no greater than 2.0 mg/dl
  SGOT and SGPT no greater than 3 x ULN

Renal:
  Creatinine no greater than 2.0 mg/dl

Cardiovascular:
  LVEF greater than 40%
  No known pericardial disease
  No active CHF
  No clinically significant dysrhythmia
  No unstable angina within 6 months
  No MI within 6 months

Pulmonary:
  No significant lung disease

Other:
  No CNS infection or uncontrolled infection
  Negative HIV serology
  No known hypersensitivity to rodent proteins
  No second malignancy within 5 years except:
     In situ cervical carcinoma
     Basal cell skin carcinoma
  No pregnant or nursing women

Blood/body fluid analyses and imaging/exams for tumor measurement completed
within 14 days prior to treatment

Expected Enrollment

20 patients will be entered.

Outline

The following acronyms are used:
  Anti-B4-bR  Murine Monoclonal Antibody Anti-B4 conjugated to blocked Ricin,
              NSC-639185
  CTX         Cyclophosphamide, NSC-26271
  DOX         Doxorubicin, NSC-123127
  EPOCH       VP-16/PRED/VCR/CTX/DOX
  PRED        Prednisone, NSC-10023
  VCR         Vincristine, NSC-67574
  VP-16       Etoposide, NSC-141540

Biological Response Modifier Therapy followed by 5-Drug Combination 
Chemotherapy.  Anti-B4-bR; followed by EPOCH.

Trial Contact Information

Trial Lead Organizations

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

Arnold Stephen Freedman, MD, Protocol chair		Ph: 617-632-3441; 866-790-4500 Email: arnold_freedman@dfci.harvard.edu