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A Phase II Clinical Trial of Anti-Tac(Fv)-PE38 (LMB-2) Immunotoxin for CD25 Positive Hairy Cell Leukemia

Phase 2
18 Years
Open (Enrolling)
Positive Hairy Cell Leukemia, CD25-Expressing Hairy Cell Leukemia

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Trial Information

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

Inclusion Criteria


1. Histopathological evidence of CD25+ HCL confirmed by the NIH pathology
department. This will require a monoclonal population of peripheral malignant
lymphocytes that are CD25 positive by fluorescence activated cell sorting (FACS)
with anti-CD25 antibody. Positive expression in a FACS assay is defined as more
than 2 times the mean fluorescence intensity (MFI) of the control antibody by
FACS. HCLv (HCL variant) is usually CD25 negative, and eligibility would
require CD25+ HCLv.

2. At least one of the following indications for treatment: neutropenia (ANC less
than 1000 cells/ microL), anemia (Hgb less than 10g/dL), thrombocytopenia (Plt
less than 100,000/ microL), an absolute lymphocyte count of greater than 20,000
cells/microL or symptomatic splenomegaly.

3. Previous treatment with or inability to receive BL22 recombinant immunotoxin.
Patients must have received cladribine with less than 2 year CR/PR after their
course of primary cladribine therapy or less than 4 year CR-PR after a 2nd or
later course of cladribine.

4. ECOG performance status of 0 - 2.

5. At least 18 years old.

6. Understand and give informed consent.

7. A negative pregnancy test in female patients of childbearing potential. Women
must not be breast-feeding.

8. ALT and AST less than or equal to 5-times the upper limits of normal. Albumin
greater than or equal to 3.0 gm/dL. Total bilirubin less than or equal to 2.2

9. Creatinine less than or equal to 1.4 mg/dL or creatinine clearance greater than
or equal to 50 ml/min.

10. Serum that neutralizes less than or equal to 75% of the activity of 1 microg/mL
of LMB-2 using a bioassay.

11. No systemic cytotoxic chemotherapy within 4 weeks of enrollment or systemic
steroids (except stable doses of Prednisone less than or equal to 20 mg/day, or
up to 4 doses of steroid given for non-therapy reasons) within 4 weeks of

12. No monoclonal antibody therapy within 12 weeks of enrollment.

13. No prior treatment with LMB-2.

14. Patients may not be receiving any other investigational agents.

15. Patients should not have uncontrolled intercurrent illness including, but not
limited to, symptomatic congestive heart failure, unstable angina pectoris,
cardiac arrhythmia, or psychiatric illness/social situations that would limit
compliance with study requirements.


- Patients who have HIV or hepatitis C. Patients would not be excluded for hepatitis B
surface antigen positivity if on Lamivudine.

- Patients receiving coumadin.

- Patients with a left ventricular ejection fraction of less than 45%.

- Patients with a DLCO less than 55% of normal or an FEV1 less than 60% of normal.

- Patients who have an active 2nd malignancy requiring systemic treatment.

Type of Study:


Study Design:

Allocation: Non-Randomized, Primary Purpose: Treatment

Outcome Measure:

Response rate

Safety Issue:


Principal Investigator

Robert J Kreitman, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Institute (NCI)


United States: Federal Government

Study ID:




Start Date:

April 2006

Completion Date:

April 2014

Related Keywords:

  • Positive Hairy Cell Leukemia
  • CD25-Expressing Hairy Cell Leukemia
  • Biologic Therapy
  • Monoclonal Antibody
  • Immunotherapy
  • Pseudomonas Exotoxin
  • Targeted Therapy
  • Hairy Cell Leukemia
  • HCL
  • Leukemia
  • Leukemia, Hairy Cell



National Institutes of Health Clinical Center, 9000 Rockville Pike Bethesda, Maryland  20892