A Phase II Clinical Trial of Anti-Tac(Fv)-PE38 (LMB-2) Immunotoxin for CD25 Positive Hairy Cell Leukemia
Background: About 80% of patients with hairy cell leukemia (HCL) have malignant cells that
express CD25 (Tac or IL2R alpha ). Normal resting B- and T-cells do not express CD25.
LMB-2 is an anti-CD25 recombinant immunotoxin containing variable domains of MAb anti-Tac
and truncated Pseudomonas exotoxin. A phase I trial at NCI found that the MTD of LMB-2 was
40 microg/Kg IV given every other day for 3 doses (QOD x3). The most common adverse events
were transient fever, hypoalbuminemia and transaminase elevations. In that trial, 4 of 4
patients with chemoresistant HCL had major responses, including one complete (CR) and 3
partial remissions. The patient with CR entered the trial transfusion dependent and now
still has normal hemoglobin and platelet counts over 7 years later. Because HCL is more
frequently CD22+ than CD25+ (100 vs 80%), HCL patients were subsequently treated with the
anti-CD22 recombinant immunotoxin BL22 and no further HCL patients were treated with LMB-2.
BL22 has induced 25 CRs out of 51 evaluable HCL patients. LMB-2 may be useful in patients
incompletely responding to BL22, because it may distribute more evenly through extravascular
sites of disease. Moreover, BL22 but not LMB-2 has caused hemolytic uremic syndrome (HUS)
in 7 patients, 6 with HCL, and several of these patients could benefit by LMB-2. Thus,
LMB-2 may be a useful and potentially lifesaving agent in patients who are unable to receive
or who have not responded adequately to BL22.
Objectives: The purpose of this study is to determine the activity of anti-Tac(Fv)-PE38
(LMB-2) in patients with CD25-expressing hairy cell leukemia (HCL). The primary endpoint of
this trial is response rate. We will also evaluate response duration, LMB-2 immunogenicity,
pharmacokinetics, toxicity, and monitor soluble Tac levels in the serum.
Eligibility: Patients must have CD25+ HCL cells by flow cytometry, cytopenia or high
circulating HCL count, prior treatment with or inability to receive BL22, prior treatment
with cladribine, ECOG PS 0-2, at least 18 years old, ALT and AST grade 0-2, albumin grade
0-1, bilirubin less than or equal to 2.2, creatinine less than or equal to 1.4 or
creatinine clearance greater than or equal to 50, lack of high levels of neutralizing
antibodies, lack of systemic treatment for 4 weeks, no prior treatment with LMB-2, lack of
other uncontrolled illness including 2nd malignancy, no HIV or hepatitis C positivity, no
coumadin therapy, LVEF greater than or equal to 45%, DLCO greater than or equal to 55%, and
FEV1 greater than or equal to 60%.
Design: Patients will receive LMB-2 at 40 microg/Kg QOD x3 at intervals of at least 25 days
for up to 6 cycles. Retreatment is permitted in the absence of neutralizing antibodies or
progressive disease. Patients in CR may receive 2 consolidation cycles, or 4 consolidation
cycles if CR is with minimal residual disease.
Dose level: LMB-2 40 microg/Kg QOD x3
Expected Accrual: 5-10 patients/year, total of 25 patients
Allocation: Non-Randomized, Primary Purpose: Treatment
Robert J Kreitman, M.D.
National Cancer Institute (NCI)
United States: Federal Government
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