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 I Treatment Closed over 18 and under 65 DFCI-89078 NCI-V90-0069

Objectives

I.  Determine the maximum tolerated dose and appropriate Phase II dose of 
anti-B4/blocked-ricin conjugate administered by continuous infusion over 7 
days to patients with B-cell leukemias and lymphomas.
II.  Determine the qualitative and quantitative clinical toxicities of 
increasing doses of anti-B4/blocked-ricin conjugate administered on this 
schedule.
III.  Evaluate the toxicity of administering anti-B4/blocked-ricin conjugate 
on this schedule and repeated, in the absence of human anti-mouse 
immunoglobulin response, at 4-week intervals.
IV.  Study the pharmacokinetics and biodistribution of increasing doses of 
anti-B4/blocked-ricin conjugate administered on this schedule.
V.  Determine whether anti-B4/blocked-ricin administered by constant infusion 
selectively binds in vivo to B4-positive normal and neoplastic cells in 
peripheral blood, bone marrow, and, if possible, in tissues.
VI.  Determine whether anti-B4/blocked-ricin conjugate selectively depletes 
normal B-cell function in vivo.
VII.  Assess tumor response during escalation and at the MTD of 
anti-B4/blocked-ricin conjugate.
VIII.  Determine whether human antibody is produced against the 
anti-B4/blocked-ricin conjugate.

Entry Criteria

Disease Characteristics:

See General Eligibility Criteria

Patient Characteristics:

See General Eligibility Criteria

General Eligibility Criteria:

Patients over 18 and under 65 years 
of age with histologically confirmed non-T-cell acute lymphoblastic leukemia, 
B-cell chronic lymphocytic leukemia, or B-cell non-Hodgkin's lymphoma that has 
relapsed following conventional primary and salvage regimens and demonstrates 
failure to respond to any regimen of proven therapeutic benefit for the 
malignancy involved.  Pathology must be reviewed at DFCI and the Department of 
Pathology at the Brigham and Women's Hospital.  Tumor cells must demonstrate 
reactivity with the anti-B4 monoclonal antibody by either flow cytometric 
analysis or immunoperoxidase.  Tissue from the time of original diagnosis, at 
relapse, or at the time of consideration for this protocol is acceptable; 
however, rebiopsy should be undertaken in all patients unless it is clinically 
contraindicated.  No prior treatment with monoclonal antibodies as serotherapy 
is allowed, and patients with a known hypersensitivity to rodent proteins are 
ineligible.  At least 3 weeks must have elapsed since any prior therapy 
including chemotherapy, radiotherapy, or major surgery; patients must not be 
on corticosteroids at the time of treatment.  CNS infiltration by tumor or 
infection, elevated CNS protein, and prior CNS irradiation to more than 2,400 
rads or within 2 months exclude.  An ECOG performance status of 0-2 and an 
expected survival of more than 2 months are required, as is adequate organ 
function demonstrated as follows:  WBC greater than 3,000, PMN greater than 
1,000, Hct greater than 25%, and platelets greater than 100,000 (patients with 
documented bone marrow involvement with malignancy may be entered, at the 
discretion of the protocol chairman, despite low peripheral blood counts); 
total bilirubin less than 2.0 mg/dl and SGOT less than 90 IU; and creatinine 
less than 2.0 mg/dl.  Known pericardial or cardiac disease including 
myocardial infarction, congestive heart failure, clinically significant 
cardiac dysrhythmia, and other clinically significant cardiac symptoms 
exclude; an ejection fraction greater than 40%, no change of more than 10% 
from a prior ejection of fraction, and a normal EKG are required.  There must 
be no clinically significant pulmonary symptoms or co-morbid disease of the 
lungs and liver; an FEV1/FEC and a TLC of greater than 60% of predicted and a 
DLCO of greater than 50% of predicted are required.  The following conditions 
exclude:  uncontrolled infection including active, invasive, or 
life-threatening fungal or viral infection and positive HIV serology (HIV test 
required); concomitant malignancy other than in situ cancer of the cervix and 
basal cell carcinoma of the skin; and pregnancy or lactation.  Concurrent 
radiotherapy or cytotoxic chemotherapy is not allowed.

Expected Enrollment

At least 3 patients will be entered per dose level studied; an additional 8-12 
patients will be entered at the MTD.

Outline

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

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

Lee Nadler, MD, Protocol chair		Ph: 617-632-3331; 866-790-4500