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, Phase I Treatment Closed physiologic 18 to 74 DFCI-90147 NCI-V91-0144

Objectives

I.  Evaluate the objective response rate produced by monoclonal antibody 
anti-B4/blocked ricin immunoconjugate (anti-B4/bR) administered by continuous 
infusion for 7 days every 14 days in patients with B-cell non-Hodgkin's 
lymphoma, B-cell CLL, and non-T-cell ALL.

II.  Evaluate the duration of response and overall survival of these patients 
treated with this agent.

III.  Assess the frequency and severity of clinical toxicity when anti-B4/bR 
is administered by continuous infusion for 7 days q 14 days.

IV.  Determine the number of courses of anti-B4/bR that can be administered at 
14-day intervals, and assess the toxicity and response at the end of each 
course.

V.  Assess the frequency of human anti-mouse and anti-ricin immunoglobulin 
production in patients who are treated with this regimen.

VI.  Determine the MTD of the new anti-B4/bR made by the "locked in process", 
at participating centers.

Entry Criteria

Disease Characteristics:

Histologically confirmed ALL, CLL, or NHL accrued sequentially
in the following 2 cohorts:

  Cohort 1:

     Stage III/IV low-grade B-cell non-Hodgkin's lymphoma
     previously untreated or treated with no more than 2
     prior chemotherapy regimens

     Symptomatic Rai Stage I, and Stage II/III/IV CLL
     previously untreated or in relapse following no more than
     2 prior chemotherapy regimens

  Cohort 2:

     Non-T-cell ALL in relapse following conventional primary
     and/or salvage chemotherapy regimens

     Intermediate- or high-grade B-cell non-Hodgkin's
     lymphoma in relapse following conventional primary
     chemotherapy regimens

Tumor cell (from original diagnosis, at relapse, or at entry)
reactivity with the anti-B4 monoclonal antibody must be
determined by either flow cytometry or immunohistochemical
staining with immunoperoxidase

  NHL demonstrating reactivity with anti-B1 antibody or L-26
  is eligible

No history of CNS involvement

Prior/Concurrent Therapy:

Biologic therapy:
  No prior monoclonal antibodies, ricin, or ricin derivatives
     as serotherapy

Chemotherapy:
  At least 3 weeks since prior chemotherapy
  No concurrent chemotherapy

Endocrine therapy:
  No corticosteroid therapy at entry

Radiotherapy:
  At least 3 weeks since prior radiotherapy
  No concurrent radiotherapy

Surgery:
  At least 3 weeks since prior major surgery

Patient Characteristics:

Age:  
  Physiologic age over 18 to under 75

Performance status:
  ECOG 0-2

Life expectancy:
  More than 2 months

Hematopoietic:
  (without transfusion)
  WBC greater than 2,500
  Platelets greater than 75,000
  Hct greater than 25%
  (suppressed counts in patients with documented bone marrow
  involvement permitted at the discretion of the study
  sponsor)

Hepatic:
  Bilirubin less than 1.2 x ULN
  SGOT and SGPT less than 2.5 x ULN
  PT and PTT within normal limits
  No past or current significant liver disease

Renal:
  Creatinine less than 1.2 x ULN

Cardiovascular:
  No known pericardial or cardiac disease, e.g.:
     No active CHF
     No clinically significant dysrhythmia

Pulmonary:
  No significant co-morbid lung disease

Other:
  No known hypersensitivity to rodent proteins (by history or
     prior anaphylaxis)
  No CNS infection
  No other uncontrolled infection (including active,
     invasive, or life-threatening fungal or viral infection)
  HBsAg seronegative
  HIV seronegative (refusal of HIV testing excludes)
  No second malignancy within 5 years except:
     In situ carcinoma of the cervix
     Basal cell skin carcinoma
  No other life-threatening illness unrelated to current
     malignancy
  No pregnant or nursing women

Expected Enrollment

Initially, 16 patients with low-grade B-cell NHL and 16 with B-cell CLL will 
be accrued; if at least 2 responses are seen in a disease category, 9 
additional patients will be accrued in that category.  If this 2-stage accrual 
is satisfactorily completed for these first 2 categories, patients with 
intermediate- or high-grade NHL and non-T-cell ALL will be accrued using the 
same sampling design.  An accrual rate of 10 patients per month is anticipated 
for this multicenter trial. As of 12/92, a limited-institution dose escalation 
study will be performed to determine the MTD of a new formulation of 
anti-B4/bR; at least 3 patients with low-grade NHL will be accrued to each 
dose level studied.

Outline

Nonrandomized study.

Biological Response Modifier Therapy.  Monoclonal Antibody Anti-B4 conjugated 
with blocked Ricin, MOAB Anti-B4/bR. 

Grossbard ML, O'Day S, Gribben JG, et al.: A phase II study of anti-B4-blocked ricin (anti-B4-bR) therapy following autologous bone marrow transplatation (ABMT) for B-cell non-Hodgkin's lymphoma (B-NHL). [Abstract] Proceedings of the American Society of Clinical Oncology 13: A-951, 293, 1994.

Grossbard ML, Gribben JG, Freedman AS, et al.: Adjuvant therapy with anti-B4-blocked ricin (anti-B4-bR) after autologous bone marrow transplantation (ABMT) for B-cell non-Hodgkin's lymphoma (B-NHL). [Abstract] Proceedings of the American Society of Clinical Oncology 12: A-1265, 373, 1993.

Trial Contact Information

Trial Lead Organizations

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

Steven O'Day, MD, Protocol chair		Ph: 310-582-7900