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 NCI BRMP-9106B NCI-91-C-222B, NCI-T91-0166N, T91-0166

Objectives

I.  Evaluate the objective response rate produced by anti-B4/blocked-ricin 
conjugate 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 produced by this 
agent in this patient population.

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

IV.  Determine the number of courses of this agent that can be administered on 
this schedule, 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 agent on this schedule.

Entry Criteria

Disease Characteristics:

Histologically confirmed B-cell malignancies entered in the
following 2 sequential patient cohorts:

  Cohort 1:
     Stage III/IV (Ann Arbor) low-grade B-cell non-Hodgkin's
     lymphoma previously untreated or treated with no more
     than 2 prior chemotherapy regimens and not requiring
     immediate medical or local therapy (entry closed as of
     10/92)

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

  Cohort 2:
     Non-T ALL in relapse following conventional primary
     and/or salvage chemotherapy regimens (failure on or
     ineligibility for salvage therapy with high-dose
     chemotherapy and bone marrow transplantation required)

     Intermediate- or high-grade B-cell non-Hodgkin's
     lymphoma in relapse following or refractory to
     conventional primary chemotherapy regimens (entry closed
     as of 10/92)

Tumor cells from original diagnosis or time of relapse must
demonstrate reactivity with anti-B4 monoclonal antibody
either by flow cytometry or immunohistochemistry

No history of CNS infiltration by tumor

Prior/Concurrent Therapy:

Biologic therapy:
  No prior mouse 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 major surgery

Patient Characteristics:

Age:
  18 and over

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%

  Low peripheral counts allowed with documented marrow
  involvement, at discretion of sponsor

Hepatic:
  Bilirubin less than 1.2 x ULN
  SGOT/SGPT less than 2.5 x ULN
  PT/PTT within normal limits
  No clinically significant liver disease

Renal:
  Creatinine less than 1.2 x ULN

Cardiovascular:
  No known pericardial or cardiac disease including:
     No active CHF
     No clinically significant dysrhythmia

Pulmonary:
  No significant co-morbid disease of the lungs

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

Expected Enrollment

In the initial patient cohort (B-cell CLL and low-grade B-cell NHL), if at 
least 2 of the first 16 patients achieve CR or PR, 9 additional patients will 
be entered.  Once study of this initial patient cohort is satisfactorily 
completed, accrual of the second patient cohort (intermediate- and high-grade 
NHL and non-T-cell ALL) will proceed with the same 2-stage sampling design.  
As of 10/92, accrual is closed to patients with NHL.

Outline

Nonrandomized study.

Biological Response Modifier Therapy.  Murine Monoclonal Antibody Anti-B4 
conjugated with A-chain-blocked Ricin, Anti-B4/blocked ricin.

Trial Contact Information

Trial Lead Organizations

Clinical Research Branch

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